Multiple Interventions Related to Dialysis Procedures in Order to Reduce Cardiovascular Morbidity and Mortality in HD Patients(EGESTUDY)

Phase 4

Completed

• Conditions: Hemodialysis; End-stage Renal Disease
• Interventions: Procedure: ultrapure dialysate; Procedure: conventional dialysate; Procedure: high-flux membrane; Procedure: low-flux membrane

• Registration Number: NCT00295191
• Lead Sponsor: Ege University

Brief Summary

This study aims to investigate the effects of high flux dialyser use and ultra pure dialysate utilization on cardiovascular disease by evaluating cardiovascular morbidity and mortality, progression of carotid artery intima-media thickness and coronary artery calcifications, inflammatory state, lipid levels, nutritional status, and erythropoietin requirement in hemodialysis patient population. It is hypothesized that both interventions in this project may diminish cardiovascular disease in hemodialysis patients.

Detailed Description

This proposed prospective, randomized, controlled study aims to investigate the effects of high flux dialyser use and ultra pure dialysate utilization on cardiovascular disease by evaluating cardiovascular morbidity and mortality, progression of carotid artery intima-media thickness and coronary artery calcifications, inflammatory state, lipid levels, nutritional status, and erythropoietin requirement in hemodialysis patient population. It is hypothesized that both interventions in this project may diminish cardiovascular disease in hemodialysis patients.

Their beneficial effects may be directly represented by significantly reduced cardiovascular morbidity and mortality. The proposed additional investigations, such as a possible decrease in the progression of coronary artery calcification and carotid artery intima-media thickness, will help us to understand the mechanisms of the expected reduction or serve as surrogate markers of atherosclerosis, in case the benefit of the interventions cannot be proven with statistical significance.

Seven hundred and four hemodialysis patients treated in Ege University Hospital Dialysis Unit and eight FMC Clinics will be enrolled into the study (3-year follow-up; percentage of yearly expected end-point 10%;expected event-free survival rate for control group during three year is 72.9%,a bilateral alpha risk equal to 5%; an 90% power to detect an increase of 15% in event-free survival at the end of 3-year follow-up in favor of the each intervention group). Annual drop-out rate is estimated as %15-20.

It is designed as 2x2 factorial; the cases, first, will be randomized to high flux dialyser and low flux dialyser arms; then, they will be re-randomized to ultra pure (online-produced by using Diasafe and checked by endotoxin measurement) and standard dialysate arms. The study will last three years; an intermediate analysis will be performed at the 18th month.

Primary end-point is the composite of cardiovascular mortality and myocardial infarction, stroke, revascularization, unstable angina pectoris requiring hospitalization (at 18 ad 36th month).

Secondary end-points are overall mortality, progression of coronary artery calcification, progression of carotid artery intima-media thickness, changes in post-dialysis body weight and upper mid-arm circumference, hematocrit and related rHu-EPO doses, changes in the levels of albumin, transferrin, total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol, high sensitive CRP, and β-2 microglobulin.

At the 0-18-36 months, coronary artery calcification will be assessed by multi-slice CT and carotid artery intima-media thickness by B-mode ultrasonography. Lipids and CRP will be measured in every three months.

Study Timeline

• Study Start: 2005-11
• Study First Submitted: 2006-02-22
• Study First Submitted QC: 2006-02-22
• Study First Posted: 2006-02-23
• Primary Completion: 2010-03
• Study Completion: 2010-03
• Status Verified: 2011-10
• Last Update Submitted: 2011-10-03
• Last Update Posted: 2011-10-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 704

Inclusion Criteria

• Aged between 18 and 80 years
• On maintenance bicarbonate hemodialysis scheduled thrice weekly, at least 12 hours/week
• Willingness to participate in the study with a written informed consent.

Exclusion Criteria

• To be scheduled for living donor renal transplantation
• To have serious life-limiting co-morbid situations; namely active malignancy, active infection, end-stage cardiac, pulmonary, or hepatic disease; pregnancy or lactating

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
4	ultrapure dialysate	ultrapure dialysate
3	conventional dialysate	conventional dialysate
1	high-flux membrane	high-flux dialyser
2	low-flux membrane	low-flux dialyser

Primary Outcome Measures

Name	Time	Method
cardiovascular mortality, myocardial infarction, stroke, unstable angina pectoris requiring hospitalization, revascularization	three years

Secondary Outcome Measures

Name	Time	Method
progression of coronary artery calcification	three years
changes in upper mid-arm circumference	three years
changes in the levels of albumin, transferrin, total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol, high sensitive CRP, and β-2 microglobulin.	three years
progression of carotid artery intima-media thickness	three years
changes in post-dialysis body weight	three years
changes in hematocrit and related rHu-EPO doses	three years
overall mortality	three years

Trial Locations

Locations (2)

Ege University School of Medicine; 🇹🇷 Bornova-Izmir, Turkey

FMC Clinics; 🇹🇷 Bornova, Izmir, Turkey