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Ultrafiltration Profiling and Outcomes Among Individuals on Maintenance Hemodialysis

Primary Purpose

End Stage Renal Disease

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

UF profiling during HD

Conventional HD

About this trial

This is an interventional treatment trial for End Stage Renal Disease focused on measuring Ultrafiltration profiling, Hemodialysis, Dialysis, Cardiovascular outcomes, Patient-reported outcomes, Crossover study design, End Stage Renal Disease, Ultrafiltration, Echocardiogram, Blood pressure, Hypotension, Symptoms

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

UF rate >10 mL/h/kg in >30% of treatments in a 30-day screening period (require ≥6 outpatient HD treatments in this period)
Age 18-85 years
Ability to converse comfortably in English or Spanish
Receipt of in-center maintenance HD at Carolina Dialysis clinics in Carrboro or Siler City, North Carolina
≥90 days on HD
Free of bloodstream infection during screening period
Willingness to undergo all study testing
Evidence of a signed and dated informed consent document

Exclusion Criteria:

Systolic BP unable to be measured by arm cuff
>1 hospitalization during screening period
Unstable angina per treating nephrologist
End-stage cirrhosis per treating nephrologist
New York Heart Association class IV heart failure per treating nephrologist
Pregnant
More than 4 times per week HD
Incarcerated
Anticipated kidney transplant within 6 months per treating nephrologist
Non-adherence to HD prescription (>2 unexplained absences during screening period)
Sodium profiling or UF profiling in standard HD prescription
Decisionally challenged, unable to provide informed consent

Sites / Locations

Carolina Dialysis - Carrboro
Carolina Dialysis - Siler City

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

UF Profiling Phase First

Conventional HD Phase First

Arm Description

First treatment phase begins with linear UF profiling during HD. Participants randomized to starting with the experimental UF profiling phase will receive 9 HD treatments with UF profiling (1st experimental phase). Following a 3 conventional HD treatment wash-out period, participants will then cross over to 9 conventional HD treatments (1st control phase). Following a 2nd 3 conventional HD treatment wash-out period, participants will cross over to 9 HD treatments with UF profiling (2nd experimental phase). Following a 3rd conventional HD treatment wash-out period, participants will cross over to 9 conventional HD treatments (2nd control phase).

First treatment phase begins with conventional HD. Participants randomized to starting with the control conventional HD phase will receive 9 conventional HD treatments (1st control phase). Following a 3 conventional HD treatment wash-out period, participants will then cross over to 9 HD treatments with UF profiling (1st experimental phase). Following a 2nd 3 conventional HD treatment wash-out period, participants will cross over to 9 conventional HD treatments (2nd control phase). Following a 3rd conventional HD treatment wash-out period, participants will cross over to 9 HD treatments with UF profiling (2nd experimental phase).

Outcomes

Primary Outcome Measures

Occurrence of Intradialytic Hypotension (Intradialytic Hypotension Defined as Nadir Systolic BP <90 mmHg)

Intradialytic blood pressure (BP) was measured with an upper extremity cuff in seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Intradialytic hypotension was defined as the presence of a nadir systolic BP <90 mmHg. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).

Pre- to Post-hemodialysis Treatment Change in Troponin T Level in ng/mL at Weeks 3, 7, 11, and 15, Using Mixed Model Analysis

Troponin T blood samples were collected at 4 study visits. Specifically, at the 7th hemodialysis treatment in each respective study phase (i.e., at week 3, 7, 11, and 15 study visits). Pre- to post-hemodialysis troponin T change was calculated as: post-dialysis troponin T - pre-dialysis troponin T (ng/mL). A lower change value reflects less cardiac strain. Based on the pre-specified protocol, the reported values represent change in troponin T between pre- and post-hemodialysis using mixed model (repeated measures logistic regression) analysis that considered all specified time-points (i.e., weeks 3, 7, 11, and 15).

Occurrence of a ≥10% Troponin T Percentage Rise From Pre- to Post-hemodialysis Treatment

Troponin T blood samples were collected before and after each participant's 7th hemodialysis treatment of each study phase (4 times during the study). Troponin T percentage change was calculated as [(Post-HD troponin T - pre-HD troponin T) / pre-HD troponin T] x100. Troponin T percentage rise was defined as a troponin T percentage change ≥10%. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).

Change From Baseline in Percent Left Ventricular Global Longitudinal Strain (GLS)

Left ventricular GLS was measured with transthoracic echocardiography at baseline and at 30 minutes before HD treatment end during the 7th treatment in the first phase of each arm. Left ventricular GLS change was calculated as peak intradialytic stress GLS - baseline GLS (%). A lower change value reflects lesser cardiac strain. Median differences were estimated using Wilcoxon (Mann-Whitney) tests.

Secondary Outcome Measures

Nadir Systolic Blood Pressure During Hemodialysis in mmHg

Intradialytic BP was measured with an upper extremity cuff in seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Nadir systolic BP was defined as the lowest intradialytic systolic BP measurement during each hemodialysis treatment. Lower values reflect greater cardiac strain. Beta-coefficients were estimated using a mixed model (repeated measures linear regression model).

Occurrence of Failed Target Weight Achievement (Failed Target Weight Achievement Defined as a Difference in Prescribed Target Weight and Post-dialysis Weight That is >1 kg or <-1 kg)

The treating nephrologist prescribed the target weight per routine clinical care. Post-dialysis weight was measured after each hemodialysis treatment in the standing position, per dialysis clinic protocol. Failed target weight achievement was defined as a difference in prescribed target weight and post-dialysis weight that was >1 kg or <-1 kg. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).

Occurrence of Patient-reported Clinically Important Cramping During Dialysis (Clinically Important Cramping Defined as Moderate, Severe, or Very Severe Cramping)

Participants' dialysis-related symptoms (e.g. cramping) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important cramping was defined as cramping ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).

Occurrence of Patient-reported Clinically Important Nausea or Upset Stomach During Dialysis (Clinically Important Nausea or Upset Stomach Defined as Moderate, Severe, or Very Severe Nausea or Upset Stomach)

Participants' dialysis-related symptoms (e.g. nausea or upset stomach) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important nausea/upset stomach was defined as nausea/upset stomach ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).

Occurrence of Patient-reported Clinically Important Vomiting or Throwing up During Dialysis (Clinically Important Vomiting or Throwing up Defined as Moderate, Severe, or Very Severe Vomiting or Throwing up)

Participants' dialysis-related symptoms (e.g. vomiting or throwing up) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important vomiting/throwing up was defined as vomiting/throwing up ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).

Occurrence of Patient-reported Clinically Important Dizziness or Lightheadedness During Dialysis (Clinically Important Dizziness or Lightheadedness Defined as Moderate, Severe, or Very Severe Dizziness or Lightheadedness)

Participants' dialysis-related symptoms (e.g. dizziness or lightheadedness) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important dizziness/lightheadedness was defined as dizziness/lightheadedness ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).

Occurrence of Patient-reported Clinically Important Racing Heart or Heart Palpitations During Dialysis (Clinically Important Racing Heart or Heart Palpitations Defined as Moderate, Severe, or Very Severe Racing Heart or Heart Palpitations)

Participants' dialysis-related symptoms (e.g. racing heart or heart palpitations) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important racing heart/heart palpitations was defined as racing heart/heart palpitations ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).

Occurrence of Patient-reported Clinically Important Chest Pain During Dialysis (Clinically Important Chest Pain Defined as Moderate, Severe, or Very Severe Chest Pain)

Participants' dialysis-related symptoms (e.g. chest pain) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important chest pain was defined as chest pain ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).

Occurrence of Patient-reported Clinically Important Shortness of Breath During Dialysis (Clinically Important Shortness of Breath Defined as Moderate, Severe, or Very Severe Shortness of Breath)

Participants' dialysis-related symptoms (e.g. shortness of breath) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important shortness of breath was defined as shortness of breath ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).

Occurrence of Patient-reported Clinically Important Thirst or Dry Mouth During Dialysis (Clinically Important Thirst or Dry Mouth Defined as Moderate, Severe, or Very Severe Thirst or Dry Mouth)

Participants' dialysis-related symptoms (e.g. thirst or dry mouth) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important thirst/dry mouth was defined as thirst/dry mouth ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).

Occurrence of Patient-reported Clinically Important Headache During Dialysis (Clinically Important Headache Defined as Moderate, Severe, or Very Severe Headache)

Participants' dialysis-related symptoms (e.g. headache) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important headache was defined as headache ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).

Occurrence of Patient-reported Clinically Important Itching During Dialysis (Clinically Important Itching Defined as Moderate, Severe, or Very Severe Itching)

Participants' dialysis-related symptoms (e.g. itching) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important itching was defined as itching ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).

Occurrence of Patient-reported Clinically Important Restless Legs During Dialysis (Clinically Important Restless Legs Defined as Moderate, Severe, or Very Severe Restless Legs)

Participants' dialysis-related symptoms (e.g. restless legs) during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important restless legs was defined as restless legs ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).

Occurrence of Patient-reported Clinically Important Tingling or Feeling of Pins and Needles During Dialysis (Clinically Important Tingling or Feeling of Pins and Needles Defined as Moderate, Severe, or Very Severe Tingling or Feeling of Pins and Needles)

Participants' dialysis-related symptoms (e.g. tingling or feeling of pins and needles during the last week were assessed using an investigator-developed 12-question symptom questionnaire administered once weekly throughout the study (6 times per study arm). Each symptom was graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Clinically important tingling/feeling of pins and needles was defined as tingling/feeling of pins and needles ranked as moderate, severe or very severe. Odds ratios were estimated using a mixed model (repeated measures logistic regression model).

Full Information

NCT ID

NCT03301740

First Posted

September 21, 2017

Last Updated

May 14, 2020

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

NCT03301740

Brief Title

Ultrafiltration Profiling and Outcomes Among Individuals on Maintenance Hemodialysis

Official Title

Ultrafiltration Profiling and Outcomes Among Individuals on Maintenance Hemodialysis

Study Type

Interventional

2. Study Status

Record Verification Date

January 2019

Overall Recruitment Status

Completed

Study Start Date

March 12, 2018 (Actual)

Primary Completion Date

December 15, 2018 (Actual)

Study Completion Date

December 18, 2018 (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

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The rate of fluid removal (ultrafiltration, UF) during hemodialysis (HD) may contribute to cardiovascular morbidity and mortality among individuals receiving maintenance HD. More rapid UF rates are associated with higher morbidity and mortality. Ultrafiltration profiling, the practice of varying UF rates to maximize fluid removal during periods of greatest hydration and plasma oncotic pressures, is one treatment modification that may reduce UF-related harm without necessitating reduction in interdialytic fluid intake or longer HD treatments. To date, UF profiling has not been adequately studied independent of sodium profiling. This study investigates the comparative effect of UF profiling versus non-profiled conventional HD on select cardiovascular and patient-reported outcomes. Participants will complete two phases of UF profiling and two phases of conventional HD and will act as their own controls.

6. Conditions and Keywords

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

End Stage Renal Disease

Keywords

Ultrafiltration profiling, Hemodialysis, Dialysis, Cardiovascular outcomes, Patient-reported outcomes, Crossover study design, End Stage Renal Disease, Ultrafiltration, Echocardiogram, Blood pressure, Hypotension, Symptoms

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Model Description

The study is a 4-phase crossover trial in which participants are successively alternated between conventional HD and conventional HD + linear UF profiling across 4 phases with intervening wash-out periods. The study compares conventional HD (the participant's standard HD prescription with no UF profiling) to conventional HD + linear UF profiling. Participants will be randomly allocated to conventional HD or conventional HD + linear UF profiling for phase 1. Participants will undergo 9 treatments during each phase for a total of 18 conventional HD treatments and 18 UF profiled treatments. Participants will undergo 3 wash-out HD treatments between phases.

Masking

ParticipantInvestigatorOutcomes Assessor

Masking Description

The study will be double-blinded in that participants will not be informed of the treatment paradigm. Investigators, including those performing transthoracic echocardiography (TTE) interpretation, will be blinded to treatment paradigm. Ultrasonographers performing intra-HD TTEs will be blinded to treatment paradigm.

Allocation

Randomized

Enrollment

34 (Actual)

8. Arms, Groups, and Interventions

Arm Title

UF Profiling Phase First

Arm Type

Experimental

Arm Description

Arm Title

Conventional HD Phase First

Arm Type

Experimental

Arm Description

Intervention Type

Other

Intervention Name(s)

UF profiling during HD

Intervention Description

Experimental arm: Linear UF profiling (linearly decreasing UF rate with a UF rate starting at 1.33 times the rate that would be needed at a constant UF rate to achieve the desired post-weight; pre-programmed "profile 2" on a Fresenius 2008K machine, the machine used in all participating clinics). Ultrafiltration profiling will be performed using Fresenius 2008K dialysis machines in accordance with manufacturer instructions.

Intervention Type

Other

Intervention Name(s)

Conventional HD

Intervention Description

Control arm: Conventional HD (routine care) is the participant's standard HD prescription without UF profiling.

Primary Outcome Measure Information:

Title

Occurrence of Intradialytic Hypotension (Intradialytic Hypotension Defined as Nadir Systolic BP <90 mmHg)

Description

Time Frame

Every study hemodialysis treatment, up to 36 treatments per participant over 15 weeks

Title

Pre- to Post-hemodialysis Treatment Change in Troponin T Level in ng/mL at Weeks 3, 7, 11, and 15, Using Mixed Model Analysis

Description

Time Frame

Weeks 3, 7, 11, and 15

Title

Occurrence of a ≥10% Troponin T Percentage Rise From Pre- to Post-hemodialysis Treatment

Description

Time Frame

Weeks 3, 7, 11, and 15

Title

Change From Baseline in Percent Left Ventricular Global Longitudinal Strain (GLS)

Description

Time Frame

Weeks 3 and 7

Secondary Outcome Measure Information:

Title

Nadir Systolic Blood Pressure During Hemodialysis in mmHg

Description

Time Frame

Every study hemodialysis treatment, up to 36 treatments per participant over 15 weeks

Title

Occurrence of Failed Target Weight Achievement (Failed Target Weight Achievement Defined as a Difference in Prescribed Target Weight and Post-dialysis Weight That is >1 kg or <-1 kg)

Description

Time Frame

Every study hemodialysis treatment, up to 36 treatments per participant over 15 weeks

Title

Occurrence of Patient-reported Clinically Important Cramping During Dialysis (Clinically Important Cramping Defined as Moderate, Severe, or Very Severe Cramping)

Description

Time Frame