Multiple Interventions Related to Dialysis Procedures in Order to Reduce Cardiovascular Morbidity and Mortality in HD Patients(EGESTUDY)
Condition: End-stage Renal Disease; Hemodialysis
MeSH terms: Kidney Diseases; Kidney Failure, Chronic
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): high-flux membrane; low-flux membrane; conventional dialysate; ultrapure dialysate
Intervention type(s): Procedure; Procedure; Procedure; Procedure
Intervention description(s): high-flux dialyser; low-flux dialyser; conventional dialysate; ultrapure dialysate
Intervention MeSH terms: Dialysis Solutions
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: end-stage renal disease; hemodialysis; cardiovascular morbidity and mortality; high flux dialyser; ultrapure dialysate; coronary vascular calcifications; carotid intima-media thickness; atherosclerosis