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Diuretic Use in Hemodialysis Patients With Residual Renal Function (DIURESED)

Primary Purpose

End Stage Renal Disease on Dialysis

Status
Recruiting
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
Furosemide
Chlorthalidone
Sponsored by
University of Alberta
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for End Stage Renal Disease on Dialysis

Eligibility Criteria

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

Inclusion Criteria: Adult patients (age 18 years or older), who are within their first 12 months of chronic (expected to need dialysis for at least 6 months), in-centre hemodialysis therapy, and Residual renal function defined as 24-hour urine volume >200cc, and Life expectancy of at least 6 months, and Participants must be able to understand the consent process and be able to sign a consent form or have a substitute decision maker who is able to understand and sign consent on their behalf. In the case of non-English speaking participants, a translator service will be used to provide study information and obtain consent. Exclusion Criteria: Unable to complete baseline urine collection Documented allergy or adverse reaction to furosemide or chlorthalidone. Unable to take oral medications Patients expecting to change modality (peritoneal dialysis, home dialysis) or to receive a renal transplant in the next 6 weeks History of hypokalemia (<3.0 mmol/L), hypomagnesemia (<0.6mmol/L), or hypocalcaemia (<1.9mmol/L) in preceding 2 weeks. Already participating in another study and one of the studies could interfere with the other study Use of loop, or thiazide diuretic medications in the last week (if a patient is on chronic diuretics, they would need to be discontinued for 1 week before starting the trial)

Sites / Locations

  • University of AlbertaRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Diuretic Therapy

Arm Description

Outcomes

Primary Outcome Measures

Change in 24-hour urine output
Change in urine output measured from 24-hour urine collection.
Change in 24-hour urine output
Change in urine output measured from 24-hour urine collection.
Change in 24-hour urine output
Change in urine output measured from 24-hour urine collection.
Change in 24-hour urine output
Change in urine output measured from 24-hour urine collection.
Change in 24-hour urine output
Change in urine output measured from 24-hour urine collection.
Change in residual renal function
Calculated based on weekly bloodwork (urea and creatinine levels) and 24-hour urine collection.
Change in residual renal function
Calculated based on weekly bloodwork (urea and creatinine levels) and 24-hour urine collection.
Change in residual renal function
Calculated based on weekly bloodwork (urea and creatinine levels) and 24-hour urine collection.
Change in residual renal function
Calculated based on weekly bloodwork (urea and creatinine levels) and 24-hour urine collection.
Change in residual renal function
Calculated based on weekly bloodwork (urea and creatinine levels) and 24-hour urine collection.

Secondary Outcome Measures

Interdialytic weight gain
Patient weight measured in kilograms
Interdialytic weight gain
Patient weight measured in kilograms
Interdialytic weight gain
Patient weight measured in kilograms
Interdialytic weight gain
Patient weight measured in kilograms
Interdialytic weight gain
Patient weight measured in kilograms
Patient-reported outcomes - ESAS-r
Patient reported outcomes using the Edmonton Symptom Assessment System-revised (ESAS-r) questionnaire.
Patient-reported outcomes - ESAS-r
Patient reported outcomes using the Edmonton Symptom Assessment System-revised (ESAS-r) questionnaire.
Patient-reported outcomes - ESAS-r
Patient reported outcomes using the Edmonton Symptom Assessment System-revised (ESAS-r) questionnaire.
Patient-reported outcomes - ESAS-r
Patient reported outcomes using the Edmonton Symptom Assessment System-revised (ESAS-r) questionnaire.
Patient-reported outcomes - ESAS-r
Patient reported outcomes using the Edmonton Symptom Assessment System-revised (ESAS-r) questionnaire.
Patient-reported outcomes - Muscle cramps
Patient reported outcomes using a muscle cramps question.
Patient-reported outcomes - Muscle cramps
Patient reported outcomes using a muscle cramps question.
Patient-reported outcomes - Muscle cramps
Patient reported outcomes using a muscle cramps question.
Patient-reported outcomes - Muscle cramps
Patient reported outcomes using a muscle cramps question.
Patient-reported outcomes - Muscle cramps
Patient reported outcomes using a muscle cramps question.
Adverse effects
Adverse effects based on symptoms and weekly bloodwork.
Adverse effects
Adverse effects based on symptoms and weekly bloodwork.
Adverse effects
Adverse effects based on symptoms and weekly bloodwork.
Adverse effects
Adverse effects based on symptoms and weekly bloodwork.
Adverse effects
Adverse effects based on symptoms and weekly bloodwork.
Urine furosemide levels
Urine furosemide levels from weekly urine samples
Urine furosemide levels
Urine furosemide levels from weekly urine samples
Urine furosemide levels
Urine furosemide levels from weekly urine samples

Full Information

First Posted
June 13, 2023
Last Updated
June 30, 2023
Sponsor
University of Alberta
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1. Study Identification

Unique Protocol Identification Number
NCT05915286
Brief Title
Diuretic Use in Hemodialysis Patients With Residual Renal Function
Acronym
DIURESED
Official Title
Diuretic Use in Hemodialysis Patients With Residual Renal Function: a Proof of Concept Study
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 29, 2023 (Actual)
Primary Completion Date
February 1, 2024 (Anticipated)
Study Completion Date
February 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Alberta

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This pilot trial will evaluate the use of diuretic medications (furosemide and chlorthalidone) in participants on dialysis to see if these medications work to preserve existing kidney function, increase urine output, and reduce weight gain between dialysis treatments. Diuretics, which are sometimes called water pills, help the body to get rid of salt (sodium) and water. There are currently no guidelines for the use of diuretic medications in dialysis patients, including the type to use, or how much to use.
Detailed Description
Fluid overload, or extracellular fluid volume expansion, in patients on hemodialysis is an important predictor of mortality. It is associated with hypertension and left ventricular hypertrophy - both risk factors for cardiovascular disease. In the United States, 80% of patients receiving hemodialysis have hypertension and 40% of patients on hemodialysis die from cardiovascular disease. The pathophysiology of hypertension in these patients is multifactorial, however, combined excess fluid and sodium is a key contributor. While ultrafiltration (removal of fluid through dialysis) is important in managing fluid overload, fluid removed by hemodialysis is a non-physiological process which imposes hemodynamic stress on the cardiovascular system in uremic patients. This system is already maladaptive as a result of decreased baroreceptor sensitivity and increased vascular stiffness, leading to higher risk of hemodynamic instability when fluid is removed from the intravascular compartment. In patients who are anuric, restriction of fluid and sodium intake and ultrafiltration are the only options for volume control. In patients who continue to produce urine, however, optimizing the amount of urine produced could improve fluid overload and decrease cardiovascular stress. Previous studies have shown that patients on hemodialysis who have residual renal function have better volume and sodium control. Higher residual renal function and higher urine output lead to a lower interdialytic weight gain in patients receiving hemodialysis; each of these factors have been associated with lower mortality. One intervention that may increase or help maintain residual renal function and increase urine output and therefore reduce interdialytic weight gain is diuretic therapy, which promotes the excretion of sodium and water by the native kidneys. Questions remain regarding the dose-response of the drug furosemide, about the utility of adding the drug chlorthalidone, and their clinical affects. The main objective of this study is to determine the effects of starting, and escalating doses of diuretic medications (furosemide +/- chlorthalidone) on 24-hour urine output (volume) over a five-week period in patients on hemodialysis who produce >200cc per day of urine. Secondary objectives are: To evaluate the effect of diuretic medications on residual renal function To evaluate the effect of different doses of diuretics on interdialytic weight gain, ultrafiltration rates and intradialytic hypotension To examine the effect of diuretics on patient reported outcomes To evaluate adverse effects of different doses of diuretics To measure serum furosemide levels in this patient population

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
End Stage Renal Disease on Dialysis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Model Description
All participants enrolled in this proof-of-concept study will be treated with the intervention (diuretic medications) in escalating doses over the study period. Each participant will act as their own control with 2 weeks of no treatment followed by the intervention for 3 weeks.
Masking
None (Open Label)
Allocation
N/A
Enrollment
34 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Diuretic Therapy
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Furosemide
Intervention Description
Each participant will have a 2 week period of no diuretic use followed by 3 weeks of escalating doses: 1) initially furosemide twice daily, then (2) an increased dose of furosemide twice daily, and in the final week, (3) the addition of chlorthalidone once daily.
Intervention Type
Drug
Intervention Name(s)
Chlorthalidone
Intervention Description
Each participant will have a 2 week period of no diuretic use followed by 3 weeks of escalating doses: 1) initially furosemide twice daily, then (2) an increased dose of furosemide twice daily, and in the final week, (3) the addition of chlorthalidone once daily.
Primary Outcome Measure Information:
Title
Change in 24-hour urine output
Description
Change in urine output measured from 24-hour urine collection.
Time Frame
Week 1
Title
Change in 24-hour urine output
Description
Change in urine output measured from 24-hour urine collection.
Time Frame
Week 2
Title
Change in 24-hour urine output
Description
Change in urine output measured from 24-hour urine collection.
Time Frame
Week 3
Title
Change in 24-hour urine output
Description
Change in urine output measured from 24-hour urine collection.
Time Frame
Week 4
Title
Change in 24-hour urine output
Description
Change in urine output measured from 24-hour urine collection.
Time Frame
Week 5
Title
Change in residual renal function
Description
Calculated based on weekly bloodwork (urea and creatinine levels) and 24-hour urine collection.
Time Frame
Week 1
Title
Change in residual renal function
Description
Calculated based on weekly bloodwork (urea and creatinine levels) and 24-hour urine collection.
Time Frame
Week 2
Title
Change in residual renal function
Description
Calculated based on weekly bloodwork (urea and creatinine levels) and 24-hour urine collection.
Time Frame
Week 3
Title
Change in residual renal function
Description
Calculated based on weekly bloodwork (urea and creatinine levels) and 24-hour urine collection.
Time Frame
Week 4
Title
Change in residual renal function
Description
Calculated based on weekly bloodwork (urea and creatinine levels) and 24-hour urine collection.
Time Frame
Week 5
Secondary Outcome Measure Information:
Title
Interdialytic weight gain
Description
Patient weight measured in kilograms
Time Frame
Week 1
Title
Interdialytic weight gain
Description
Patient weight measured in kilograms
Time Frame
Week 2
Title
Interdialytic weight gain
Description
Patient weight measured in kilograms
Time Frame
Week 3
Title
Interdialytic weight gain
Description
Patient weight measured in kilograms
Time Frame
Week 4
Title
Interdialytic weight gain
Description
Patient weight measured in kilograms
Time Frame
Week 5
Title
Patient-reported outcomes - ESAS-r
Description
Patient reported outcomes using the Edmonton Symptom Assessment System-revised (ESAS-r) questionnaire.
Time Frame
Week 1
Title
Patient-reported outcomes - ESAS-r
Description
Patient reported outcomes using the Edmonton Symptom Assessment System-revised (ESAS-r) questionnaire.
Time Frame
Week 2
Title
Patient-reported outcomes - ESAS-r
Description
Patient reported outcomes using the Edmonton Symptom Assessment System-revised (ESAS-r) questionnaire.
Time Frame
Week 3
Title
Patient-reported outcomes - ESAS-r
Description
Patient reported outcomes using the Edmonton Symptom Assessment System-revised (ESAS-r) questionnaire.
Time Frame
Week 4
Title
Patient-reported outcomes - ESAS-r
Description
Patient reported outcomes using the Edmonton Symptom Assessment System-revised (ESAS-r) questionnaire.
Time Frame
Week 5
Title
Patient-reported outcomes - Muscle cramps
Description
Patient reported outcomes using a muscle cramps question.
Time Frame
Week 1
Title
Patient-reported outcomes - Muscle cramps
Description
Patient reported outcomes using a muscle cramps question.
Time Frame
Week 2
Title
Patient-reported outcomes - Muscle cramps
Description
Patient reported outcomes using a muscle cramps question.
Time Frame
Week 3
Title
Patient-reported outcomes - Muscle cramps
Description
Patient reported outcomes using a muscle cramps question.
Time Frame
Week 4
Title
Patient-reported outcomes - Muscle cramps
Description
Patient reported outcomes using a muscle cramps question.
Time Frame
Week 5
Title
Adverse effects
Description
Adverse effects based on symptoms and weekly bloodwork.
Time Frame
Week 1
Title
Adverse effects
Description
Adverse effects based on symptoms and weekly bloodwork.
Time Frame
Week 2
Title
Adverse effects
Description
Adverse effects based on symptoms and weekly bloodwork.
Time Frame
Week 3
Title
Adverse effects
Description
Adverse effects based on symptoms and weekly bloodwork.
Time Frame
Week 4
Title
Adverse effects
Description
Adverse effects based on symptoms and weekly bloodwork.
Time Frame
Week 5
Title
Urine furosemide levels
Description
Urine furosemide levels from weekly urine samples
Time Frame
Week 3
Title
Urine furosemide levels
Description
Urine furosemide levels from weekly urine samples
Time Frame
Week 4
Title
Urine furosemide levels
Description
Urine furosemide levels from weekly urine samples
Time Frame
Week 5

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adult patients (age 18 years or older), who are within their first 12 months of chronic (expected to need dialysis for at least 6 months), in-centre hemodialysis therapy, and Residual renal function defined as 24-hour urine volume >200cc, and Life expectancy of at least 6 months, and Participants must be able to understand the consent process and be able to sign a consent form or have a substitute decision maker who is able to understand and sign consent on their behalf. In the case of non-English speaking participants, a translator service will be used to provide study information and obtain consent. Exclusion Criteria: Unable to complete baseline urine collection Documented allergy or adverse reaction to furosemide or chlorthalidone. Unable to take oral medications Patients expecting to change modality (peritoneal dialysis, home dialysis) or to receive a renal transplant in the next 6 weeks History of hypokalemia (<3.0 mmol/L), hypomagnesemia (<0.6mmol/L), or hypocalcaemia (<1.9mmol/L) in preceding 2 weeks. Already participating in another study and one of the studies could interfere with the other study Use of loop, or thiazide diuretic medications in the last week (if a patient is on chronic diuretics, they would need to be discontinued for 1 week before starting the trial)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Melissa Schorr, MD
Phone
(226) 448-4837
Email
Melissa.Schorr@albertahealthservices.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Branko Braam, MD/Ph.D
Phone
(780) 492-1867
Email
braam@ualberta.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Branko Braam, MD/Ph.D.
Organizational Affiliation
University of Alberta
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alberta
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2B7
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Melissa Schorr, MD
Phone
2264484837
Email
Melissa.Schorr@albertahealthservices.ca
First Name & Middle Initial & Last Name & Degree
Melissa Schorr, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Diuretic Use in Hemodialysis Patients With Residual Renal Function

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