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Pilot Study of Loop Diuretics Among Individuals Receiving Hemodialysis

Primary Purpose

Chronic Kidney Disease Requiring Chronic Dialysis

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Furosemide (loop diuretic) Tablets

About this trial

This is an interventional treatment trial for Chronic Kidney Disease Requiring Chronic Dialysis focused on measuring Hemodialysis, Dialysis, End Stage Renal Disease, Patient-reported Outcomes, Symptoms, Diuretic, Furosemide, Lasix

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patient self-report of at least 1 cup urine/24-hours
Age ≥18 years
Receipt of thrice weekly in-center HD at a participating clinic (UNC-associated Carolina Dialysis- Carrboro, Siler City, Pittsboro, Sanford, and Lee County)
≥60 days receiving in-center HD
Willingness to take study medication and undergo study testing
Ability to provide informed consent

Exclusion Criteria:

Known allergy to loop diuretic
History of poor adherence to HD or medical regimen per nephrologist
>1 hospitalization in prior 30-days
Frequent hypotension (systolic BP <80 mmHg at >30% of HD treatments in prior 30-days)
Cirrhosis per nephrologist
Hearing disorder per nephrologist
Serum potassium <3.5 mEq/L, magnesium <1 mg/dL, or corrected calcium <8 mg/dL in prior 30-days
Taking a non-loop diuretic (e.g. spironolactone, eplerenone, ethacrynic acid, thiazides)
Taking an aminoglycoside, cisplatin, methotrexate, cyclosporine, adrenocorticotropic hormone (ACTH), lithium, phenytoin, or oral/intravenous steroid
Natural licorice consumption
Prisoners, patients with significant mental illness
Pregnant patients and nursing mothers

Sites / Locations

Carolina Dialysis - Carrboro
Carolina Dialysis - Pittsboro
Carolina Dialysis - Sanford
Carolina Dialysis - Lee County
Carolina Dialysis - Siler City

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Study drug administration: furosemide

Arm Description

Study participants will receive furosemide oral tablets to be taken twice daily. During study period 1 (first 6 weeks), the drug dose will be escalated every 2 weeks if safe, tolerated, and acceptable to the participant. During study period 2 (subsequent 12 weeks), participants will take the maximum tolerated dose from study period 1, received every 4 weeks if safe, tolerated, and acceptable to the participant.

Outcomes

Primary Outcome Measures

Percentage of Participants Who Have a Defined Increase in 24-hour Urine Volume From Baseline to Week 5

Participants will follow standard dialysis clinic protocols for 24-urine volume collection. Classifying participants as has having an increase in 24-hour urine volume will be contingent on the amount of urine the participant makes at baseline. Among participants with baseline 24-hour urine volume ≥200 mL: ≥25% increase in urine volume is considered an increase. Among participants with baseline 24-hour urine volume <200 mL: ≥50 mL increase in urine volume to a urine volume of at least 100 mL/24-hours is considered an increase. The percentage of participants who have a defined increase in 24-urine volume from baseline to week 5 will be determined.

Percentage of Participants Who Have a Defined Increase in 24-hour Urine Volume From Baseline to Week 12

Percentage of Participants Who Have a Defined Increase in 24-hour Urine Volume From Baseline to Week 18

Percentage of Participants With A Serum Potassium <3.2 mEq/L at Week 1

Blood samples will be collected from participants prior to their dialysis treatments at the week 1 study visit. The percentage of participants who have a serum potassium <3.2 mEq/L will be determined.

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 2

Blood samples will be collected from participants prior to their dialysis treatments at the week 2 study visit. The percentage of participants who have a serum potassium <3.2 mEq/L will be determined.

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 3

Blood samples will be collected from participants prior to their dialysis treatments at the week 3 study visit. The percentage of participants who have a serum potassium <3.2 mEq/L will be determined.

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 4

Blood samples will be collected from participants prior to their dialysis treatments at the week 4 study visit. The percentage of participants who have a serum potassium <3.2 mEq/L will be determined.

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 5

Blood samples will be collected from participants prior to their dialysis treatments at the week 5 study visit. The percentage of participants who have a serum potassium <3.2 mEq/L will be determined.

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 6

Blood samples will be collected from participants prior to their dialysis treatments at the week 6 study visit. The percentage of participants who have a serum potassium <3.2 mEq/L will be determined.

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 9

Blood samples will be collected from participants prior to their dialysis treatments at the week 9 study visit. The percentage of participants who have a serum potassium <3.2 mEq/L will be determined.

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 13

Blood samples will be collected from participants prior to their dialysis treatments at the week 13 study visit. The percentage of participants who have a serum potassium <3.2 mEq/L will be determined.

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 17

Blood samples will be collected from participants prior to their dialysis treatments at the week 17 study visit. The percentage of participants who have a serum potassium <3.2 mEq/L will be determined.

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 1

Blood samples will be collected from participants prior to their dialysis treatments at the week 1 study visit. The percentage of participants who have a serum magnesium <0.8 mEq/L will be determined.

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 2

Blood samples will be collected from participants prior to their dialysis treatments at the week 2 study visit. The percentage of participants who have a serum magnesium <0.8 mEq/L will be determined.

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 3

Blood samples will be collected from participants prior to their dialysis treatments at the week 3 study visit. The percentage of participants who have a serum magnesium <0.8 mEq/L will be determined.

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 4

Blood samples will be collected from participants prior to their dialysis treatments at the week 4 study visit. The percentage of participants who have a serum magnesium <0.8 mEq/L will be determined.

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 5

Blood samples will be collected from participants prior to their dialysis treatments at the week 5 study visit. The percentage of participants who have a serum magnesium <0.8 mEq/L will be determined.

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 6

Blood samples will be collected from participants prior to their dialysis treatments at the week 6 study visit. The percentage of participants who have a serum magnesium <0.8 mEq/L will be determined.

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 9

Blood samples will be collected from participants prior to their dialysis treatments at the week 9 study visit. The percentage of participants who have a serum magnesium <0.8 mEq/L will be determined.

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 13

Blood samples will be collected from participants prior to their dialysis treatments at the week 13 study visit. The percentage of participants who have a serum magnesium <0.8 mEq/L will be determined.

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 17

Blood samples will be collected from participants prior to their dialysis treatments at the week 17 study visit. The percentage of participants who have a serum magnesium <0.8 mEq/L will be determined.

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 1

Blood samples will be collected from participants prior to their dialysis treatments at the week 1 study visit. The percentage of participants who have a serum corrected calcium <7.0 mg/dL will be determined.

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 2

Blood samples will be collected from participants prior to their dialysis treatments at the week 2 study visit. The percentage of participants who have a serum corrected calcium <7.0 mg/dL will be determined.

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 3

Blood samples will be collected from participants prior to their dialysis treatments at the week 3 study visit. The percentage of participants who have a serum corrected calcium <7.0 mg/dL will be determined.

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 4

Blood samples will be collected from participants prior to their dialysis treatments at the week 4 study visit. The percentage of participants who have a serum corrected calcium <7.0 mg/dL will be determined.

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 5

Blood samples will be collected from participants prior to their dialysis treatments at the week 5 study visit. The percentage of participants who have a serum corrected calcium <7.0 mg/dL will be determined.

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 6

Blood samples will be collected from participants prior to their dialysis treatments at the week 6 study visit. The percentage of participants who have a serum corrected calcium <7.0 mg/dL will be determined.

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 9

Blood samples will be collected from participants prior to their dialysis treatments at the week 9 study visit. The percentage of participants who have a serum corrected calcium <7.0 mg/dL will be determined.

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 13

Blood samples will be collected from participants prior to their dialysis treatments at the week 13 study visit. The percentage of participants who have a serum corrected calcium <7.0 mg/dL will be determined.

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 17

Blood samples will be collected from participants prior to their dialysis treatments at the week 17 study visit. The percentage of participants who have a serum corrected calcium <7.0 mg/dL will be determined.

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 1.

Blood samples will be collected from participants prior to their dialysis treatments at the week 1 study visit. The percentage of participants who have a serum furosemide level >12 micrograms/L will be determined.

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 2.

Blood samples will be collected from participants prior to their dialysis treatments at the week 2 study visit. The percentage of participants who have a serum furosemide level >12 micrograms/L will be determined.

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 3.

Blood samples will be collected from participants prior to their dialysis treatments at the week 3 study visit. The percentage of participants who have a serum furosemide level >12 micrograms/L will be determined.

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 4.

Blood samples will be collected from participants prior to their dialysis treatments at the week 4 study visit. The percentage of participants who have a serum furosemide level >12 micrograms/L will be determined.

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 5.

Blood samples will be collected from participants prior to their dialysis treatments at the week 5 study visit. The percentage of participants who have a serum furosemide level >12 micrograms/L will be determined.

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 6.

Blood samples will be collected from participants prior to their dialysis treatments at the week 6 study visit. The percentage of participants who have a serum furosemide level >12 micrograms/L will be determined.

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 9.

Blood samples will be collected from participants prior to their dialysis treatments at the week 9 study visit. The percentage of participants who have a serum furosemide level >12 micrograms/L will be determined.

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 13.

Blood samples will be collected from participants prior to their dialysis treatments at the week 13 study visit. The percentage of participants who have a serum furosemide level >12 micrograms/L will be determined.

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 17.

Blood samples will be collected from participants prior to their dialysis treatments at the week 17 study visit. The percentage of participants who have a serum furosemide level >12 micrograms/L will be determined.

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 1

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 1 will be determined.

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 2

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 3

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 4

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 5

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 6

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 7

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 8

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 9

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 10

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 11

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 12

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 13

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 14

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 15

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 16

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 17

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 18

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 1

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 2

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 3

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 4

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 5

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 6

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 8

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 10

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 12

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 14

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 16

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 18

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 1

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 2

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 3

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 4

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 5

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 6

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 8

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 10

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 12

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 14

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 16

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 18

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 1

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 2

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 3

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 4

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 5

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 6

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 8

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 10

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 12

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 14

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 16

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 18

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Change in the Inner EAR Instrument Score From Baseline to Week 1

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 1. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score.

Percentage of Participants With a Defined Decrease in the Inner EAR Instrument Score From Baseline to Week 2

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 2. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score. The percentage of participants with a defined decrease in the Inner EAR instrument score will be determined.

Change in the Inner EAR Instrument Score From Baseline to Week 3

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 3. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score.

Percentage of Participants With a Defined Decrease in the Inner EAR Instrument Score From Baseline to Week 4

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 4. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score. The percentage of participants with a defined decrease in the Inner EAR instrument score will be determined.

Change in the Inner EAR Instrument Score From Baseline to Week 5

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 5. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score.

Percentage of Participants With a Defined Decrease in the Inner EAR Instrument Score From Baseline to Week 6

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 6. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score. The percentage of participants with a defined decrease in the Inner EAR instrument score will be determined.

Change in the Inner EAR Instrument Score From Baseline to Week 8

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 8. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score.

Percentage of Participants With a Defined Decrease in the Inner EAR Instrument Score From Baseline to Week 10

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 10. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score. The percentage of participants with a defined decrease in the Inner EAR instrument score will be determined.

Change in the Inner EAR Instrument Score From Baseline to Week 12

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 12. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score.

Percentage of Participants With a Defined Decrease in the Inner EAR Instrument Score From Baseline to Week 14

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 14. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score. The percentage of participants with a defined decrease in the Inner EAR instrument score will be determined.

Change in the Inner EAR Instrument Score From Baseline to Week 16

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 16. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score.

Percentage of Participants With a Defined Decrease in the Inner EAR Instrument Score From Baseline to Week 18

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 18. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score. The percentage of participants with a defined decrease in the Inner EAR instrument score will be determined.

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 1

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 2

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 3

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 4

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 5

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 6

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 8

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 10

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 12

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 14

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 16

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 18

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 1

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 2

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 3

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 4

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 5

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 6

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 8

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 10

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 12

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 14

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 16

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 18

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 1

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 2

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 3

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 4

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 5

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 6

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 8

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 10

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 12

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 14

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 16

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 18

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 1

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 2

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 3

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 4

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 5

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 6

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 8

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 10

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 12

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 14

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 16

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 18

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 1

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 2

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 3

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 4

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 5

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 6

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 8

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 10

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 12

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 14

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 16

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 18

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 1

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 2

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 3

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 4

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 5

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 6

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 8

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 10

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 12

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 14

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 16

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 18

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 1

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 2

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 3

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 4

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 5

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 6

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 8

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 10

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 12

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 14

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 16

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 18

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Percentage of Participants Reporting Acceptance of Furosemide at Week 1

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 1. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.

Percentage of Participants Reporting Acceptance of Furosemide at Week 2

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 2. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.

Percentage of Participants Reporting Acceptance of Furosemide at Week 3

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 3. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.

Percentage of Participants Reporting Acceptance of Furosemide at Week 4

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 4. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.

Percentage of Participants Reporting Acceptance of Furosemide at Week 5

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 5. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.

Percentage of Participants Reporting Acceptance of Furosemide at Week 6

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 6. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.

Percentage of Participants Reporting Acceptance of Furosemide at Week 8

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 8. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.

Percentage of Participants Reporting Acceptance of Furosemide at Week 10

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 10. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.

Percentage of Participants Reporting Acceptance of Furosemide at Week 12

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 12. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.

Percentage of Participants Reporting Acceptance of Furosemide at Week 14

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 14. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.

Percentage of Participants Reporting Acceptance of Furosemide at Week 16

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 16. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.

Percentage of Participants Reporting Acceptance of Furosemide at Week 18

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 18. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 1

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 1. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 2

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 2. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 3

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 3. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 4

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 4. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 5

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 5. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 6

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 6. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 8

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 8. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 10

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 10. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 12

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 12. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 14

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 14. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 16

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 16. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 18

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 18. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 19

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 19. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.

Secondary Outcome Measures

Full Information

NCT ID

NCT04622709

First Posted

October 2, 2020

Last Updated

May 18, 2022

Sponsor

University of North Carolina, Chapel Hill

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

1. Study Identification

Unique Protocol Identification Number

NCT04622709

Brief Title

Pilot Study of Loop Diuretics Among Individuals Receiving Hemodialysis

Official Title

Pilot Study of Loop Diuretics Among Individuals Receiving Hemodialysis

Study Type

Interventional

2. Study Status

Record Verification Date

March 2022

Overall Recruitment Status

Completed

Study Start Date

October 7, 2020 (Actual)

Primary Completion Date

June 8, 2021 (Actual)

Study Completion Date

June 22, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of North Carolina, Chapel Hill

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Individuals with kidney failure receiving maintenance hemodialysis (HD) have high mortality rates, driven largely by cardiovascular causes. Volume-related factors are critical, modifiable contributors to cardiovascular complications. Reversing volume overload has been shown to improve blood pressure and cardiac remodeling. Use of loop diuretics may represent a pragmatic, low-cost, and low-burden strategy to improve outcomes in people receiving HD. Lack of data on optimal furosemide dosing, safety, and acceptability are barriers to expanded use. This study investigates whether oral furosemide is safe and effective at increasing urine volume in HD patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Kidney Disease Requiring Chronic Dialysis

Keywords

Hemodialysis, Dialysis, End Stage Renal Disease, Patient-reported Outcomes, Symptoms, Diuretic, Furosemide, Lasix

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Model Description

This is a single-center (multi-clinic), open-label, non-randomized pilot study to test whether oral furosemide is safe and effective at increasing urine volume in HD patients. The study will consist of 2 periods: a 6-week dose escalation period (period 1) and a subsequent 12-week follow-up period (period 2). During period 1, all participants will receive escalating doses of furosemide as tolerated, and the short-term safety, tolerability, and efficacy of furosemide will be examined. During period 2, all participants will continue the maximally tolerated period 1 furosemide dose, and the acceptability of and adherence to furosemide and the longer-term safety and efficacy of furosemide will be examined.

Masking

None (Open Label)

Allocation

N/A

Enrollment

39 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Study drug administration: furosemide

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Furosemide (loop diuretic) Tablets

Intervention Description

Open label dose escalation study of furosemide in people receiving maintenance hemodialysis. Participants will take furosemide oral tablets twice daily for 18 weeks. Doses will be titrated every 2 weeks for 6 weeks if safe, effective, tolerated, and accepted by the participant. First 2 weeks of the study: participants not taking oral furosemide at enrollment will take 80mg furosemide twice daily, those taking oral furosemide at enrollment will stay on their prescribed dose, and those taking another loop diuretic at enrollment will discontinue their prescription and take an equivalent oral furosemide dose. At week 4: dose escalation if tolerated (from 80mg to 120mg twice daily for the 1st group, and a 50% increased dose not >320mg/day for the 2nd & 3rd groups). At week 6: dose escalation if tolerated (from 120mg to 160mg twice daily for the 1st group, and a 50% increased dose not >320mg/day for the 2nd & 3rd groups). Final 12 weeks: all participants will take the maximum tolerated dose.

Primary Outcome Measure Information:

Title

Percentage of Participants Who Have a Defined Increase in 24-hour Urine Volume From Baseline to Week 5

Description

Time Frame

Baseline and study week 5 (5 weeks after study medication start

Title

Percentage of Participants Who Have a Defined Increase in 24-hour Urine Volume From Baseline to Week 12

Description

Time Frame

Baseline and study week 12 (12 weeks after study medication start)

Title

Percentage of Participants Who Have a Defined Increase in 24-hour Urine Volume From Baseline to Week 18

Description

Time Frame

Baseline and study week 18 (18 weeks after study medication start)

Title

Percentage of Participants With A Serum Potassium <3.2 mEq/L at Week 1

Description

Time Frame

Study week 1 (1 week after study medication start)

Title

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 2

Description

Time Frame

Study week 2 (2 weeks after study medication start)

Title

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 3

Description

Time Frame

Study week 3 (3 weeks after study medication start)

Title

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 4

Description

Time Frame

Study week 4 (4 weeks after study medication start)

Title

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 5

Description

Time Frame

Study week 5 (5 weeks after study medication start)

Title

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 6

Description

Time Frame

Study week 6 (6 weeks after study medication start)

Title

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 9

Description

Time Frame

Study week 9 (9 weeks after study medication start)

Title

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 13

Description

Time Frame

Study week 13 (13 weeks after study medication start)

Title

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 17

Description

Time Frame

Study week 17 (17 weeks after study medication start)

Title

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 1

Description

Time Frame

Study week 1 (1 week after study medication start)

Title

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 2

Description

Time Frame

Study week 2 (2 weeks after study medication start)

Title

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 3

Description

Time Frame

Study week 3 (3 weeks after study medication start)

Title

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 4

Description

Time Frame

Study week 4 (4 weeks after study medication start)

Title

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 5

Description

Time Frame

Study week 5 (5 weeks after study medication start)

Title

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 6

Description

Time Frame

Study week 6 (6 weeks after study medication start)

Title

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 9

Description

Time Frame

Study week 9 (9 weeks after study medication start)

Title

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 13

Description

Time Frame

Study week 13 (13 weeks after study medication start)

Title

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 17

Description

Time Frame

Study week 17 (17 weeks after study medication start)

Title

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 1

Description

Time Frame

Study week 1 (1 week after study medication start)

Title

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 2

Description

Time Frame

Study week 2 (2 weeks after study medication start)

Title

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 3

Description

Time Frame

Study week 3 (3 weeks after study medication start)

Title

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 4

Description

Time Frame

Study week 4 (4 weeks after study medication start)

Title

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 5

Description

Time Frame

Study week 5 (5 weeks after study medication start)

Title

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 6

Description

Time Frame

Study week 6 (6 weeks after study medication start)

Title

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 9

Description

Time Frame

Study week 9 (9 weeks after study medication start)

Title

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 13

Description

Time Frame

Study week 13 (13 weeks after study medication start)

Title

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 17

Description

Time Frame

Study week 17 (17 weeks after study medication start)

Title

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 1.

Description

Time Frame

Study week 1 (1 week after study medication start)

Title

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 2.

Description

Time Frame

Study week 2 (2 weeks after study medication start)

Title

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 3.

Description

Time Frame

Study week 3 (3 weeks after study medication start)

Title

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 4.

Description

Time Frame

Study week 4 (4 weeks after study medication start)

Title

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 5.

Description

Time Frame

Study week 5 (5 weeks after study medication start)

Title

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 6.

Description

Time Frame

Study week 6 (6 weeks after study medication start)

Title

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 9.

Description

Time Frame

Study week 9 (9 weeks after study medication start)

Title

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 13.

Description

Time Frame

Study week 13 (13 weeks after study medication start)

Title

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 17.

Description

Time Frame

Study week 17 (17 weeks after study medication start)

Title

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 1

Description

Time Frame

Up to study week 1 (1 week after study medication start)

Title

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 2

Description

Time Frame

Up to study week 2 (2 weeks after study medication start)

Title

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 3

Description

Time Frame

Up to study week 3 (3 weeks after study medication start)

Title

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 4

Description

Time Frame

Up to study week 4 (4 weeks after study medication start)

Title

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 5

Description

Time Frame

Up to study week 5 (5 weeks after study medication start)

Title

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 6

Description

Time Frame

Up to study week 6 (6 weeks after study medication start)

Title

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 7

Description

Time Frame

Up to study week 7 (7 weeks after study medication start)

Title

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 8

Description

Time Frame

Up to study week 8 (8 weeks after study medication start)

Title

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 9

Description

Time Frame

Up to study week 9 (9 weeks after study medication start)

Title

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 10

Description

Time Frame

Up to study week 10 (10 weeks after study medication start)

Title

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 11

Description

Time Frame

Up to study week 11 (11 weeks after study medication start)

Title

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 12

Description

Time Frame

Up to study week 12 (12 weeks after study medication start)

Title

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 13

Description

Time Frame

Up to study week 13 (13 weeks after study medication start)

Title

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 14

Description

Time Frame

Up to study week 14 (14 weeks after study medication start)

Title

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 15

Description

Time Frame

Up to study week 15 (15 weeks after study medication start)

Title

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 16

Description

Time Frame

Up to study week 16 (16 weeks after study medication start)

Title

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 17

Description

Time Frame

Up to study week 17 (17 weeks after study medication start)

Title

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 18

Description

Time Frame

Up to study week 18 (18 weeks after study medication start)

Title

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 1

Description

Time Frame

Study week 1 (1 week after study medication start)

Title

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 2

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Time Frame

Study week 2 (2 weeks after study medication start)

Title

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 3

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Time Frame

Study week 3 (3 weeks after study medication start)

Title

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 4

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Time Frame

Study week 4 (4 weeks after study medication start)

Title

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 5

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Time Frame

Study week 5 (5 weeks after study medication start)

Title

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 6

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Time Frame

Study week 6 (6 weeks after study medication start)

Title

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 8

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Time Frame

Study week 8 (8 weeks after study medication start)

Title

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 10

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Time Frame

Study week 10 (10 weeks after study medication start)

Title

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 12

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Time Frame

Study week 12 (12 weeks after study medication start)

Title

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 14

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Time Frame

Study week 14 (14 weeks after study medication start)

Title

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 16

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Time Frame

Study week 16 (16 weeks after study medication start)

Title

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 18

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.

Time Frame

Study week 18 (18 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 1

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Time Frame

Study week 1 (1 week after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 2

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Time Frame

Study week 2 (2 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 3

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Time Frame

Study week 3 (3 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 4

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Time Frame

Study week 4 (4 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 5

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Time Frame

Study week 5 (5 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 6

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Time Frame

Study week 6 (6 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 8

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Time Frame

Study week 8 (8 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 10

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Time Frame

Study week 10 (10 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 12

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Time Frame

Study week 12 (12 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 14

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Time Frame

Study week 14 (14 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 16

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Time Frame

Study week 16 (16 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 18

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.

Time Frame

Study week 18 (18 weeks after study medication start)

Title

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 1

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Time Frame

Study week 1 (1 week after study medication start)

Title

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 2

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Time Frame

Study week 2 (2 weeks after study medication start)

Title

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 3

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Time Frame

Study week 3 (3 weeks after study medication start)

Title

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 4

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Time Frame

Study week 4 (4 weeks after study medication start)

Title

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 5

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Time Frame

Study week 5 (5 weeks after study medication start)

Title

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 6

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Time Frame

Study week 6 (6 weeks after study medication start)

Title

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 8

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Time Frame

Study week 8 (8 weeks after study medication start)

Title

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 10

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Time Frame

Study week 10 (10 weeks after study medication start)

Title

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 12

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Time Frame

Study week 12 (12 weeks after study medication start)

Title

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 14

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Time Frame

Study week 14 (14 weeks after study medication start)

Title

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 16

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Time Frame

Study week 16 (16 weeks after study medication start)

Title

Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 18

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.

Time Frame

Study week 18 (18 weeks after study medication start)

Title

Change in the Inner EAR Instrument Score From Baseline to Week 1

Description

Time Frame

Baseline and study week 1 (1 week after study medication start)

Title

Percentage of Participants With a Defined Decrease in the Inner EAR Instrument Score From Baseline to Week 2

Description

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 2. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score. The percentage of participants with a defined decrease in the Inner EAR instrument score will be determined.

Time Frame

Baseline and study week 2 (2 weeks after study medication start)

Title

Change in the Inner EAR Instrument Score From Baseline to Week 3

Description

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 3. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score.

Time Frame

Baseline and study week 3 (3 weeks after study medication start)

Title

Percentage of Participants With a Defined Decrease in the Inner EAR Instrument Score From Baseline to Week 4

Description

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 4. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score. The percentage of participants with a defined decrease in the Inner EAR instrument score will be determined.

Time Frame

Baseline and study week 4 (4 weeks after study medication start)

Title

Change in the Inner EAR Instrument Score From Baseline to Week 5

Description

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 5. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score.

Time Frame

Baseline and study week 5 (5 weeks after study medication start)

Title

Percentage of Participants With a Defined Decrease in the Inner EAR Instrument Score From Baseline to Week 6

Description

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 6. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score. The percentage of participants with a defined decrease in the Inner EAR instrument score will be determined.

Time Frame

Baseline and study week 6 (6 weeks after study medication start)

Title

Change in the Inner EAR Instrument Score From Baseline to Week 8

Description

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 8. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score.

Time Frame

Baseline and study week 8 (8 weeks after study medication start)

Title

Percentage of Participants With a Defined Decrease in the Inner EAR Instrument Score From Baseline to Week 10

Description

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 10. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score. The percentage of participants with a defined decrease in the Inner EAR instrument score will be determined.

Time Frame

Baseline and study week 10 (10 weeks after study medication start)

Title

Change in the Inner EAR Instrument Score From Baseline to Week 12

Description

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 12. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score.

Time Frame

Baseline and study week 12 (12 weeks after study medication start)

Title

Percentage of Participants With a Defined Decrease in the Inner EAR Instrument Score From Baseline to Week 14

Description

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 14. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score. The percentage of participants with a defined decrease in the Inner EAR instrument score will be determined.

Time Frame

Baseline and study week 14 (14 weeks after study medication start)

Title

Change in the Inner EAR Instrument Score From Baseline to Week 16

Description

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 16. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score.

Time Frame

Baseline and study week 16 (16 weeks after study medication start)

Title

Percentage of Participants With a Defined Decrease in the Inner EAR Instrument Score From Baseline to Week 18

Description

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 18. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score. The percentage of participants with a defined decrease in the Inner EAR instrument score will be determined.

Time Frame

Baseline and study week 18 (18 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 1

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Time Frame

Study week 1 (1 week after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 2

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Time Frame

Study week 2 (2 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 3

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Time Frame

Study week 3 (3 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 4

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Time Frame

Study week 4 (4 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 5

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Time Frame

Study week 5 (5 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 6

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Time Frame

Study week 6 (6 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 8

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Time Frame

Study week 8 (8 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 10

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Time Frame

Study week 10 (10 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 12

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Time Frame

Study week 12 (12 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 14

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Time Frame

Study week 14 (14 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 16

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Time Frame

Study week 16 (16 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 18

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.

Time Frame

Study week 18 (18 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 1

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Time Frame

Study week 1 (1 week after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 2

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Time Frame

Study week 2 (2 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 3

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Time Frame

Study week 3 (3 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 4

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Time Frame

Study week 4 (4 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 5

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Time Frame

Study week 5 (5 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 6

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Time Frame

Study week 6 (6 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 8

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Time Frame

Study week 8 (8 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 10

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Time Frame

Study week 10 (10 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 12

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Time Frame

Study week 12 (12 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 14

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Time Frame

Study week 14 (14 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 16

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Time Frame

Study week 16 (16 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 18

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.

Time Frame

Study week 18 (18 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 1

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Time Frame

Study week 1 (1 week after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 2

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Time Frame

Study week 2 (2 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 3

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Time Frame

Study week 3 (3 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 4

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Time Frame

Study week 4 (4 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 5

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Time Frame

Study week 5 (5 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 6

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Time Frame

Study week 6 (6 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 8

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Time Frame

Study week 8 (8 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 10

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Time Frame

Study week 10 (10 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 12

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Time Frame

Study week 12 (12 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 14

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Time Frame

Study week 14 (14 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 16

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Time Frame

Study week 16 (16 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 18

Description

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.

Time Frame

Study week 18 (18 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 1

Description

Time Frame

Study week 1 (1 week after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 2

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Time Frame

Study week 2 (2 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 3

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Time Frame

Study week 3 (3 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 4

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Time Frame

Study week 4 (4 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 5

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Time Frame

Study week 5 (5 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 6

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Time Frame

Study week 6 (6 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 8

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Time Frame

Study week 8 (8 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 10

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Time Frame

Study week 10 (10 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 12

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Time Frame

Study week 12 (12 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 14

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Time Frame

Study week 14 (14 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 16

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Time Frame

Study week 16 (16 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 18

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.

Time Frame

Study week 18 (18 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 1

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Time Frame

Study week 1 (1 week after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 2

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Time Frame

Study week 2 (2 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 3

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Time Frame

Study week 3 (3 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 4

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Time Frame

Study week 4 (4 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 5

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Time Frame

Study week 5 (5 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 6

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Time Frame

Study week 6 (6 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 8

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Time Frame

Study week 8 (8 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 10

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Time Frame

Study week 10 (10 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 12

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Time Frame

Study week 12 (12 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 14

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Time Frame

Study week 14 (14 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 16

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Time Frame

Study week 16 (16 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 18

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.

Time Frame

Study week 18 (18 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 1

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Time Frame

Study week 1 (1 week after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 2

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Time Frame

Study week 2 (2 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 3

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Time Frame

Study week 3 (3 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 4

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Time Frame

Study week 4 (4 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 5

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Time Frame

Study week 5 (5 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 6

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Time Frame

Study week 6 (6 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 8

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Time Frame

Study week 8 (8 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 10

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Time Frame

Study week 10 (10 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 12

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Time Frame

Study week 12 (12 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 14

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Time Frame

Study week 14 (14 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 16

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Time Frame

Study week 16 (16 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 18

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.

Time Frame

Study week 18 (18 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 1

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Time Frame

Study week 1 (1 week after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 2

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Time Frame

Study week 2 (2 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 3

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Time Frame

Study week 3 (3 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 4

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Time Frame

Study week 4 (4 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 5

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Time Frame

Study week 5 (5 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 6

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Time Frame

Study week 6 (6 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 8

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Time Frame

Study week 8 (8 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 10

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Time Frame

Study week 10 (10 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 12

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Time Frame

Study week 12 (12 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 14

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Time Frame

Study week 14 (14 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 16

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Time Frame

Study week 16 (16 weeks after study medication start)

Title

Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 18

Description

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.

Time Frame

Study week 18 (18 weeks after study medication start)

Title

Percentage of Participants Reporting Acceptance of Furosemide at Week 1

Description

Time Frame

Study week 1 (1 week after study medication start)

Title

Percentage of Participants Reporting Acceptance of Furosemide at Week 2

Description

Time Frame

Study week 2 (2 weeks after study medication start)

Title

Percentage of Participants Reporting Acceptance of Furosemide at Week 3

Description

Time Frame

Study week 3 (3 weeks after study medication start)

Title

Percentage of Participants Reporting Acceptance of Furosemide at Week 4

Description

Time Frame

Study week 4 (4 weeks after study medication start)

Title

Percentage of Participants Reporting Acceptance of Furosemide at Week 5

Description

Time Frame

Study week 5 (5 weeks after study medication start)

Title

Percentage of Participants Reporting Acceptance of Furosemide at Week 6

Description

Time Frame

Study week 6 (6 weeks after study medication start)

Title

Percentage of Participants Reporting Acceptance of Furosemide at Week 8

Description

Time Frame

Study week 8 (8 weeks after study medication start)

Title

Percentage of Participants Reporting Acceptance of Furosemide at Week 10

Description

Time Frame

Study week 10 (10 weeks after study medication start)

Title

Percentage of Participants Reporting Acceptance of Furosemide at Week 12

Description

Time Frame

Study week 12 (12 weeks after study medication start)

Title

Percentage of Participants Reporting Acceptance of Furosemide at Week 14

Description

Time Frame

Study week 14 (14 weeks after study medication start)

Title

Percentage of Participants Reporting Acceptance of Furosemide at Week 16

Description

Time Frame

Study week 16 (16 weeks after study medication start)

Title

Percentage of Participants Reporting Acceptance of Furosemide at Week 18

Description

Time Frame

Study week 18 (18 weeks after study medication start)

Title

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 1

Description

Time Frame

Study week 1 (1 week after study medication start)

Title

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 2

Description

Time Frame

Study week 2 (2 weeks after study medication start)

Title

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 3

Description

Time Frame

Study week 3 (3 weeks after study medication start)

Title

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 4

Description

Time Frame

Study week 4 (4 weeks after study medication start)

Title

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 5

Description

Time Frame

Study week 5 (5 weeks after study medication start)

Title

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 6

Description

Time Frame

Study week 6 (6 weeks after study medication start)

Title

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 8

Description

Time Frame

Study week 8 (8 weeks after study medication start)

Title

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 10

Description

Time Frame

Study week 10 (10 weeks after study medication start)

Title

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 12

Description

Time Frame

Study week 12 (12 weeks after study medication start)

Title

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 14

Description

Time Frame

Study week 14 (14 weeks after study medication start)

Title

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 16

Description

Time Frame

Study week 16 (16 weeks after study medication start)

Title

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 18

Description

Time Frame

Study week 18 (18 weeks after study medication start)

Title

Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 19

Description

Time Frame

Study week 19 (19 weeks after study medication start)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patient self-report of at least 1 cup urine/24-hours Age ≥18 years Receipt of thrice weekly in-center HD at a participating clinic (UNC-associated Carolina Dialysis- Carrboro, Siler City, Pittsboro, Sanford, and Lee County) ≥60 days receiving in-center HD Willingness to take study medication and undergo study testing Ability to provide informed consent Exclusion Criteria: Known allergy to loop diuretic History of poor adherence to HD or medical regimen per nephrologist >1 hospitalization in prior 30-days Frequent hypotension (systolic BP <80 mmHg at >30% of HD treatments in prior 30-days) Cirrhosis per nephrologist Hearing disorder per nephrologist Serum potassium <3.5 mEq/L, magnesium <1 mg/dL, or corrected calcium <8 mg/dL in prior 30-days Taking a non-loop diuretic (e.g. spironolactone, eplerenone, ethacrynic acid, thiazides) Taking an aminoglycoside, cisplatin, methotrexate, cyclosporine, adrenocorticotropic hormone (ACTH), lithium, phenytoin, or oral/intravenous steroid Natural licorice consumption Prisoners, patients with significant mental illness Pregnant patients and nursing mothers

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jennifer Flythe, MD, MPH

Organizational Affiliation

University of North Carolina, Chapel Hill

Official's Role

Principal Investigator

Facility Information:

Facility Name

Carolina Dialysis - Carrboro

City

Carrboro

State/Province

North Carolina

ZIP/Postal Code

27510

Country

United States

Facility Name

Carolina Dialysis - Pittsboro

City

Pittsboro

State/Province

North Carolina

ZIP/Postal Code

27312

Country

United States

Facility Name

Carolina Dialysis - Sanford

City

Sanford

State/Province

North Carolina

ZIP/Postal Code

27330

Country

United States

Facility Name

Carolina Dialysis - Lee County

City

Sanford

State/Province

North Carolina

ZIP/Postal Code

27332

Country

United States

Facility Name

Carolina Dialysis - Siler City

City

Siler City

State/Province

North Carolina

ZIP/Postal Code

27344

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

De-identified individual data that supports the results will be shared from 9 through 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.

IPD Sharing Time Frame

From 9 months through 36 months after publication

IPD Sharing Access Criteria

The investigator who proposes to use the data has approval from an IRB, IEC, or REB, as applicable, and an executed data use/sharing agreement with UNC.

Learn more about this trial

Pilot Study of Loop Diuretics Among Individuals Receiving Hemodialysis

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