Ultrafiltration Profiling and Outcomes Among Individuals on Maintenance Hemodialysis

NCT03301740 | Completed Results

• 2 other identifiers: 17-10571K23DK109401
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Outcome Measures

Primary Outcomes (4)

• 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).

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

• 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).

  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).

  Weeks 3, 7, 11, and 15

• 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.

  Weeks 3 and 7

Secondary Outcomes (14)

• Nadir Systolic Blood Pressure During Hemodialysis in mmHg

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

• 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)

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

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

  Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15

• 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)

  Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15

• 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)

  Weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15

Study Arms (2)

UF Profiling Phase First

EXPERIMENTAL

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).

Other: UF profiling during HD; Other: Conventional HD

Conventional HD Phase First

EXPERIMENTAL

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).

Other: UF profiling during HD; Other: Conventional HD

Interventions

UF profiling during HD OTHER

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.

Conventional HD Phase First; UF Profiling Phase First

Conventional HD OTHER

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

Conventional HD Phase First; UF Profiling Phase First

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (2)

Carolina Dialysis - Carrboro

Carrboro, North Carolina, 27510, United States

Location

Carolina Dialysis - Siler City

Siler City, North Carolina, 27344, United States

Location

Related Publications (1)

• Flythe JE, Tugman MJ, Narendra JH, Assimon MM, Li Q, Wang Y, Brunelli SM, Hinderliter AL. Effect of ultrafiltration profiling on outcomes among maintenance hemodialysis patients: a pilot randomized crossover trial. J Nephrol. 2021 Feb;34(1):113-123. doi: 10.1007/s40620-020-00862-6. Epub 2020 Sep 25.

  PMID: 32975783 DERIVED

MeSH Terms

Conditions

Kidney Failure, Chronic; Hypotension

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Jennifer E. Flythe, MD, MPH
• Organization: University of North Carolina at Chapel Hill

jflythe@med.unc.edu

(919) 445-2656

Study Officials

• Jennifer Flythe, MD, MPH

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 21, 2017
• First Posted: October 4, 2017
• Study Start: March 12, 2018
• Primary Completion: December 15, 2018
• Study Completion: December 18, 2018
• Last Updated: May 15, 2020
• Results First Posted: May 15, 2020

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)