Effect of Dialysis Dose and Membrane Flux in Maintenance Hemodialysis (HEMO)

Randomized Study of Standard vs High Amount of Hemodialysis Using Low vs High Flux Dialyzer Membranes for End Stage Renal Disease

OBJECTIVES: I. Evaluate whether hemodialysis providing a 2-pool, variable volume urea kinetic modelling value of 1.05 versus 1.45 reduces mortality and morbidity in patients with end stage renal disease.

II. Compare the efficacy of high versus low flux dialyzer membranes.

Study Overview

• Status: Completed
• Conditions: End Stage Renal Disease
• Intervention / Treatment: Device: Standard dose, low flux hemodialysis; Device: Standard dose, high flux hemodialysis; Device: High dose, low flux hemodialysis; Device: High dose, high flux hemodialysis

Detailed Description

PROTOCOL OUTLINE: This is a randomized, multicenter study. Patients are stratified by center, age, and diabetes prior to dialysis initiation.

Patients are randomly assigned to 1 of 4 groups: moderate dose dialysis, low flux membrane; high dose dialysis, low flux membrane; moderate dose dialysis, high flux membrane; or high dose dialysis, high flux membrane. Moderate dose is a target eKt/V of 1.05 and high dose is 1.45. The dose and delivery of dialysis are measured monthly by the equilibrated fractional clearance of urea (eKt/V) calculated with double pool kinetics.

Patients are dialyzed 3 times a week in the shortest possible time (minimum 2.5 hours), adjusted for adequate fluid removal. General medical care, protein and calorie intake, and dialyzer reuse and other aspects of dialysis therapy are standardized. The protocol document lists approved dialyzers; no unsubstituted cellulosic membranes are permitted.

The intervention phase of this study is 5 years. Patients are followed for survival.

• Study Type: Interventional
• Enrollment (Actual): 1846
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• End stage renal disease that requires in-center hemodialysis 3 times/week On hemodialysis for at least 3 months (6 months following renal transplant)
• No scheduled renal transplant from living donor

--Prior/Concurrent Therapy--

• No concurrent intervention studies unless ancillary to this protocol No concurrent investigational drugs

--Patient Characteristics--

• Hepatic: Albumin at least 2.6 g/dL by nephelometry No cirrhosis with encephalopathy or abnormal PT
• Renal: Urea clearance (interdialytic) no greater than 1.5 mL/min per 35 liters total urea volume
• Cardiovascular: No New York Heart Association class IV congestive heart failure despite maximal therapy No unstable angina No new onset angina No recent exacerbation of frequency, duration, or severity of angina
• Pulmonary: No chronic pulmonary disease requiring supplemental oxygen
• Other: Not hospitalized in acute or long term care facility at entry No active malignancy requiring chemotherapy or radiotherapy No AIDS No active systemic infection, e.g., tuberculosis or fungal infection No mental incompetence or other contraindication to protocol therapy Not pregnant Geographically available for treatment at participating institution No more than 20 missed treatments/year

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard dose, low flux hemodialysis	Device: Standard dose, low flux hemodialysis
Experimental: Standard dose, high flux hemodialysis	Device: Standard dose, high flux hemodialysis
Experimental: High dose, low flux hemodialysis	Device: High dose, low flux hemodialysis
Experimental: High dose, high flux hemodialysis	Device: High dose, high flux hemodialysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Death from any cause	5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
First hospitalization for cardiac causes or death from any cause	5 years
First hospitalization for infection or death from any cause	5 years
First >15% decrease in albumin or death from any cause	5 years
All hospitalizations not related to vascular access	5 years
Death due to cardiac causes	5 years
First hospitalization or death due to cardiac causes	5 years
Death due to infection	5 years
First hospitalization or death due to infection	5 years

Collaborators and Investigators

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Collaborators: Washington University School of Medicine; University of Alabama at Birmingham; Icahn School of Medicine at Mount Sinai; The Cleveland Clinic; University of Illinois at Chicago; Emory University; Duke University; Brigham and Women's Hospital; University of California, Davis; Wake Forest University Health Sciences; Vanderbilt University; University of Texas Southwestern Medical Center; Tufts Medical Center; University of Utah; University of Rochester; Main Line Health; Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
• Investigators: Study Chair: Daniel B. Ornt, University of Rochester

Publications and helpful links

General Publications

• Greene T, Beck GJ, Gassman JJ, Gotch FA, Kusek JW, Levey AS, Levin NW, Schulman G, Eknoyan G. Design and statistical issues of the hemodialysis (HEMO) study. Control Clin Trials. 2000 Oct;21(5):502-25. doi: 10.1016/s0197-2456(00)00062-3.
• Eknoyan G, Beck GJ, Cheung AK, Daugirdas JT, Greene T, Kusek JW, Allon M, Bailey J, Delmez JA, Depner TA, Dwyer JT, Levey AS, Levin NW, Milford E, Ornt DB, Rocco MV, Schulman G, Schwab SJ, Teehan BP, Toto R; Hemodialysis (HEMO) Study Group. Effect of dialysis dose and membrane flux in maintenance hemodialysis. N Engl J Med. 2002 Dec 19;347(25):2010-9. doi: 10.1056/NEJMoa021583.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 1995
• Primary Completion (Actual): December 31, 2001
• Study Completion (Actual): December 31, 2001

Study Registration Dates

• First Submitted: October 18, 1999
• First Submitted That Met QC Criteria: October 18, 1999
• First Posted (Estimate): October 19, 1999

Study Record Updates

• Last Update Posted (Actual): September 14, 2017
• Last Update Submitted That Met QC Criteria: September 13, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: rare disease; end stage renal disease; renal and genitourinary disorders
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Diseases; Kidney Failure, Chronic
• Other Study ID Numbers: 199/11704; U01DK046109 (U.S. NIH Grant/Contract); U01DK046114 (U.S. NIH Grant/Contract); U01DK046126 (U.S. NIH Grant/Contract); U01DK046140 (U.S. NIH Grant/Contract); U01DK046143 (U.S. NIH Grant/Contract); U01DK049240 (U.S. NIH Grant/Contract); U01DK049241 (U.S. NIH Grant/Contract); U01DK049242 (U.S. NIH Grant/Contract); U01DK049243 (U.S. NIH Grant/Contract); U01DK049244 (U.S. NIH Grant/Contract); U01DK049249 (U.S. NIH Grant/Contract); U01DK049252 (U.S. NIH Grant/Contract); U01DK049254 (U.S. NIH Grant/Contract); U01DK049259 (U.S. NIH Grant/Contract); U01DK049261 (U.S. NIH Grant/Contract); U01DK049264 (U.S. NIH Grant/Contract); U01DK049271 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data and samples are available at the NIDDK central repository
• IPD Sharing Time Frame: Available since 2009
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes