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Effect of Increased Convective Clearance by On-Line Hemodiafiltration on All Cause Mortality in Chronic Hemodialysis Patients (CONTRAST)

This study has been completed.
Sponsor:
Collaborators:
UMC Utrecht
Medical Center Alkmaar
Maasstad Hospital
Julius Center for Health Sciences and Primary Care, Utrecht
Dutch Kidney Foundation
Fresenius Medical Care North America
Gambro Renal Products, Inc.
Baxter Healthcare Corporation
Roche Pharma AG
Information provided by:
VU University Medical Center
ClinicalTrials.gov Identifier:
NCT00205556
First received: September 12, 2005
Last updated: January 20, 2011
Last verified: January 2011

September 12, 2005
January 20, 2011
June 2004
December 2010   (final data collection date for primary outcome measure)
all cause mortality [ Time Frame: entire follow up (until dead or end of study, 1-7 years) ] [ Designated as safety issue: Yes ]
all cause mortality
Complete list of historical versions of study NCT00205556 on ClinicalTrials.gov Archive Site
  • fatal and non-fatal cardiovascular events [ Time Frame: entire follow up (until death or end of study, 1-7 years) ] [ Designated as safety issue: No ]
  • Left ventricular mass index (LVMi), carotid IMT (intima media thickness), aortic pulse wave velocity (PWV) [ Time Frame: first 3 years ] [ Designated as safety issue: No ]
  • laboratory markers of endothelial dysfunction, micro-inflammation, oxidative stress [ Time Frame: first three years of follow up ] [ Designated as safety issue: No ]
  • lipid profiles, uremic toxins [ Time Frame: first three years ] [ Designated as safety issue: No ]
  • quality of life [ Time Frame: entire follow up (until death or end of study, 1-7 years) ] [ Designated as safety issue: No ]
  • nutritional state [ Time Frame: entire follow up (until death or end of study 1-7 years) ] [ Designated as safety issue: No ]
  • anemia management [ Time Frame: first 12 months of follow up ] [ Designated as safety issue: No ]
    hemoglobin levels, erythropoietin use / resistance iron saturation / ferritin levels, prescription of iron medication
  • cost utility analysis [ Time Frame: entire follow up (until death or end of study, 1-7 years) ] [ Designated as safety issue: No ]
  • hospital admissions [ Time Frame: entire follow up (until death or end of study, 1-7 years) ] [ Designated as safety issue: No ]
    hospitalization days hospital admission for infections hospital admission for any cause
  • blood pressure and antihypertensive medication [ Time Frame: entire follow up (until death or end of study, 1-7 years) ] [ Designated as safety issue: No ]
  • residual kidney function [ Time Frame: entire follow up (until death or end of study, 1-7 years) ] [ Designated as safety issue: No ]
  • mineral bone disease [ Time Frame: entire follow up (until death or end of study, 1-7 years) ] [ Designated as safety issue: No ]
    laboratory parameters of mineral bone disease and medication (phosphate binders, vitamin D (or analogues), cinacalet)
  • parameters of treatment / treatment delivery [ Time Frame: entire follow up (until death or end of study, 1-7 years) ] [ Designated as safety issue: No ]
    dialysis efficiency (Kt/V urea); bloodflow, dialysate flow, ultrafiltration volume, (HDF:) convection volume
  • fatal and non-fatal cardiovascular events
  • LVMi, carotid IMT, aortic PWV
  • laboratory markers of endothelial dysfunction, micro-inflammation, oxidative stress
  • lipid profiles, uremic toxins
  • quality of life
  • nutritional state
Not Provided
Not Provided
 
Effect of Increased Convective Clearance by On-Line Hemodiafiltration on All Cause Mortality in Chronic Hemodialysis Patients
Effect of Increased Convective Clearance by On-line Hemodiafiltration on All Cause and Cardiovascular Mortality in Chronic Hemodialysis Patients: The Dutch Convective Transport Study (CONTRAST)

The purpose of this study is to compare the effect of low flux hemodialysis with online hemodiafiltration on all cause mortality and a combination of cardiovascular morbidity and mortality in chronic hemodialysis patients.

Today, an increasing number of patients with chronic renal failure (CRF) is treated with (on-line) hemodiafiltration (HDF). This practice is based on the assumption that the high incidence of cardiovascular (CV) disease, as observed in patients with CRF, is at least partially related to the retention of uremic toxins in the middle and large-middle molecular (MM) range. As HDF lowers these molecules more effectively than HD, it has been suggested that this treatment improves CV outcome, if compared to standard HD.

Thus far, no definite data on the effects of HDF on CV parameters and/or clinical end-points are available. Promising data include a reduction of left ventricular mass index (LVMi) after one year of treatment with acetate free bio-filtration (AFB). Furthermore, relatively high survival rates were reported in a single center non-experimental study on patients who were treated with HDF, if compared to the EDTA registry data on HD-treated patients. Yet, these data are of observational nature, with the possibility of being biased by confounding by indication.

As the accumulation of MMW substances has been implicated in increased oxidative stress and endothelial dysfunction, a reduction of these compounds might improve these derangements. In addition, cardiac dysfunction, atherosclerosis (as measured by left ventricular mass index [LVMi], carotid intima media thickness [CIMT]) and vascular stiffness (as measured by pulse wave velocity [PWV]) might be reduced during HDF, as compared to low-flux HD.

Therefore, we propose a prospective, randomized multicenter trial, comparing (on-line) HDF with HD. After a stabilization period, an expected number of 700 chronic HD patients will be randomized to either HDF or low-flux HD and followed during 1-6 years. Primary end points are all cause mortality and combined CV events and mortality. In addition, LVMi, PWV, CIMT and various parameters of oxidative stress, acute phase reaction (APR) and endothelial function will be assessed and compared between treatment groups.

This study will provide strong evidence on the efficacy of HDF compared to low flux HD on CV morbidity and mortality, which is currently lacking but urgently needed. It is highly likely that the outcome of this study will affect current clinical practice considerably, in the Netherlands as well as internationally. Moreover, the study will point towards the mechanisms underlying the effects of HDF.

The following hypotheses will be tested:

  1. All-cause mortality and combined CV morbidity and mortality in patients treated with (on-line) HDF is lower than in patients treated with standard low-flux HD.
  2. A reduction in MMW uremic toxins by HDF leads to an improvement of the 'uremic profile' (as measured by AGE-levels, homocysteine levels, oxidative stress, and endothelial dysfunction), if compared to standard low-flux HD.
  3. The improvement of the 'uremic profile' in HDF-treated patients results in an improvement of endothelial function with a reduction in the progression of vascular injury (as measured by CIMT and PWV) and a reduction in LVMi, if compared to standard low-flux HD.
Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • End-stage Renal Disease
  • Cardiovascular Disease
  • Procedure: on-line hemodiafiltration
    addition of convective transport to regular dialysis treatment by using on-line hemodiafiltration
  • Procedure: low flux hemodialysis
    standard treatment
  • 1: low flux hemodialysis
    standard treatment
    Intervention: Procedure: low flux hemodialysis
  • Active Comparator: 2 on-line hemodiafiltration
    Intervention: Procedure: on-line hemodiafiltration

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
715
January 2011
December 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients treated by HD 2 or 3 times a week, for at least 2 months
  • Patients able to understand the study procedures
  • Patients willing to provide written informed consent

Exclusion Criteria:

  • Current age < 18 years
  • Treatment by HDF or high flux HD in the preceding 6 months
  • Severe incompliance (severe non-adherence to the dialysis procedure and accompanying prescriptions, especially frequency and duration of dialysis treatment and fluid restriction)
  • Life expectancy < 3 months due to non renal disease
  • Participation in other clinical intervention trials evaluating cardiovascular outcome
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Canada,   Netherlands,   Norway
 
NCT00205556
METC VUmc 03/097, ISRCTN38365125, CCMO number P03.1089L, Dutch Kidney Found C 02.2019
Yes
contact person: MPC Grooteman MD PhD, Vrije Universiteit Medical Center and University Medical Center Utrecht
VU University Medical Center
  • UMC Utrecht
  • Medical Center Alkmaar
  • Maasstad Hospital
  • Julius Center for Health Sciences and Primary Care, Utrecht
  • Dutch Kidney Foundation
  • Fresenius Medical Care North America
  • Gambro Renal Products, Inc.
  • Baxter Healthcare Corporation
  • Roche Pharma AG
Study Director: Menso J Nubé, MD PhD Medical Center Alkmaar
Study Chair: Piet M ter Wee, MD PhD Vrije Universiteit Medical Center, Amsterdam
Study Chair: Peter J Blankestijn, MD PhD Universityr Medical Center Utrecht
Study Director: René A van den Dorpel, MD PhD Medisch Centrum Rijnmond Zuid - locatie Clara, Rotterdam
Study Director: Michiel L Bots, MD PhD Julius Center for Health Sciences and Primary Care, Utrecht
Principal Investigator: Muriel PC Grooteman, MD PhD Vrije Universiteit Medical Center, Amsterdam
VU University Medical Center
January 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP