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

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

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.

Study Overview

• Status: Completed
• Conditions: Hemodialysis; End-stage Renal Disease
• Intervention / Treatment: Procedure: high-flux membrane; Procedure: low-flux membrane; Procedure: conventional dialysate; Procedure: ultrapure dialysate

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 Type: Interventional
• Enrollment (Actual): 704
• Phase: Phase 4

Contacts and Locations

Study Locations

• Turkey
  • Bornova-Izmir, Turkey, 35100
    • Ege University School of Medicine
  • Izmir
    • Bornova, Izmir, Turkey, 35100
      • FMC Clinics

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

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 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: 1; high-flux dialyser	Procedure: high-flux membrane; high-flux dialyser
Active Comparator: 2; low-flux dialyser	Procedure: low-flux membrane; low-flux dialyser
Active Comparator: 3; conventional dialysate	Procedure: conventional dialysate; conventional dialysate
Active Comparator: 4; ultrapure dialysate	Procedure: ultrapure dialysate; ultrapure dialysate

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Ege University
• Collaborators: Fresenius Medical Care North America
• Investigators: Principal Investigator: Ercan Ok, M.D, Ege University School of Medicine Nephrology Department

Publications and helpful links

General Publications

• Ok ES, Asci G, Toz H, Ritz E, Kircelli F, Sever MS, Ozkahya M, Sipahi S, Dheir H, Bozkurt D, Omer Z, Sahin OZ, Ertilav M, Ok E. Glycated hemoglobin predicts overall and cardiovascular mortality in non-diabetic hemodialysis patients. Clin Nephrol. 2014 Sep;82(3):173-80. doi: 10.5414/cn108251.

Study record dates

Study Major Dates

• Study Start: November 1, 2005
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: February 22, 2006
• First Submitted That Met QC Criteria: February 22, 2006
• First Posted (Estimate): February 23, 2006

Study Record Updates

• Last Update Posted (Estimate): October 4, 2011
• Last Update Submitted That Met QC Criteria: October 3, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: atherosclerosis; end-stage renal disease; hemodialysis; cardiovascular morbidity and mortality; high flux dialyser; ultrapure dialysate; coronary vascular calcifications; carotid intima-media thickness
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Diseases; Kidney Failure, Chronic; Pharmaceutical Solutions; Dialysis Solutions
• Other Study ID Numbers: EGE99803466003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No