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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Multiple Interventions Related to Dialysis Procedures in Order to Reduce Cardiovascular Morbidity and Mortality in Hemodialysis Patients: Prospective, Randomized, Controlled Study

Conditions
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End-stage Renal Disease, Hemodialysis

Intervention / Treatment
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* Procedure: high-flux membrane
* Procedure: low-flux membrane
* Procedure: conventional dialysate
* Procedure: ultrapure dialysate


Participation Criteria
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Eligibility Criteria
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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

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: 1<br>high-flux dialyser | Procedure: high-flux membrane<br>* high-flux dialyser<br>|
| Active Comparator: 2<br>low-flux dialyser | Procedure: low-flux membrane<br>* low-flux dialyser<br>|
| Active Comparator: 3<br>conventional dialysate | Procedure: conventional dialysate<br>* conventional dialysate<br>|
| Active Comparator: 4<br>ultrapure dialysate | Procedure: ultrapure dialysate<br>* ultrapure dialysate<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cardiovascular mortality, myocardial infarction, stroke, unstable angina pectoris requiring hospitalization, revascularization |  | three years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall mortality |  | three years | 
| progression of coronary artery calcification |  | three years | 
| progression of carotid artery intima-media thickness |  | three years | 
| changes in post-dialysis body weight |  | three years | 
| changes in upper mid-arm circumference |  | three years | 
| changes in hematocrit and related rHu-EPO doses |  | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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end-stage renal disease, hemodialysis, cardiovascular morbidity and mortality, high flux dialyser, ultrapure dialysate, coronary vascular calcifications, carotid intima-media thickness, atherosclerosis