Clinical trial NCT00295191: Multiple Interventions Related to Dialysis Procedures in Order to Reduce Cardiovascular Morbidity and Mortality in HD Patients(EGESTUDY)
Official title: Multiple Interventions Related to Dialysis Procedures in Order to Reduce Cardiovascular Morbidity and Mortality in Hemodialysis Patients: Prospective, Randomized, Controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: End-stage Renal Disease
Hemodialysis
Keywords: end-stage renal disease
hemodialysis
cardiovascular morbidity and mortality
high flux dialyser
ultrapure dialysate
coronary vascular calcifications
carotid intima-media thickness
atherosclerosis
Lead sponsor: Ege University
Sponsor class: OTHER
Collaborators: name: Fresenius Medical Care North America
First posted: 2006-02-23
Enrollment: 704
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: cardiovascular mortality, myocardial infarction, stroke, unstable angina pectoris requiring hospitalization, revascularization
timeFrame: three years
Secondary outcomes:
measure: overall mortality
timeFrame: three years
measure: progression of coronary artery calcification
timeFrame: three years
measure: progression of carotid artery intima-media thickness
timeFrame: three years
measure: changes in post-dialysis body weight
timeFrame: three years
measure: changes in upper mid-arm circumference
timeFrame: three years
measure: changes in hematocrit and related rHu-EPO doses
timeFrame: three years
measure: changes in the levels of albumin, transferrin, total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol, high sensitive CRP, and β-2 microglobulin.
timeFrame: three years
Other outcomes:
Locations:
city: Bornova
country: Turkey
facility: FMC Clinics
state: Izmir
city: Bornova-Izmir
country: Turkey
facility: Ege University School of Medicine
Study officials:
affiliation: Ege University School of Medicine Nephrology Department
name: Ercan Ok, M.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.