Effect of Dialysis Dose and Membrane Flux in Maintenance Hemodialysis

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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End Stage Renal Disease

Intervention / Treatment
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* Device: Standard dose, low flux hemodialysis
* Device: Standard dose, high flux hemodialysis
* Device: High dose, low flux hemodialysis
* Device: High dose, high flux hemodialysis


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard dose, low flux hemodialysis<br> | Device: Standard dose, low flux hemodialysis<br> <br> |
| Experimental: Standard dose, high flux hemodialysis<br> | Device: Standard dose, high flux hemodialysis<br> <br> |
| Experimental: High dose, low flux hemodialysis<br> | Device: High dose, low flux hemodialysis<br> <br> |
| Experimental: High dose, high flux hemodialysis<br> | Device: High dose, high flux hemodialysis<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death from any cause |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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end stage renal disease, rare disease, renal and genitourinary disorders