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

January 20, 2011 updated by: Amsterdam UMC, location VUmc

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

715

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
      • Montreal, Canada, H2L 4M1
        • Centre Hospitalier de L'Université de Montreal, Hopital Notre Dame
    • New Brunswick
      • Moncton, New Brunswick, Canada
        • Dr Georges-L. Dumont Regional Hospital
  • Netherlands
      • 's Hertogenbosch, Netherlands, 5200 ME
        • Jeroen Bosch Ziekenhuis
      • Alkmaar, Netherlands, 1815 JD
        • Medisch Centrum Alkmaar
      • Amsterdam, Netherlands, 1081 HV
        • Vrije Universiteit Medisch Centrum
      • Amsterdam, Netherlands, 1090 HM
        • Onze Lieve Vrouwe Gasthuis
      • Amsterdam, Netherlands, 1100 DD
        • Academical Medical Center
      • Arnhem, Netherlands, 6800 TA
        • Ziekenhuis Rijnstate
      • Beilen, Netherlands, 9411 SE
        • Dialyse Kliniek Noord
      • Den Haag, Netherlands, 2545 CH
        • Haga Ziekenhuis (locatie Leyenburg)
      • Doetinchem, Netherlands, 7009 BL
        • Slingeland Ziekenhuis
      • Ede, Netherlands, 6710 HN
        • Ziekenhuis Gelderse Vallei
      • Eindhoven, Netherlands, 5602 ZA
        • Catharina Ziekenhuis
      • Goes, Netherlands, 4460 BB
        • Oosterscheldeziekenhuis
      • Gouda, Netherlands
        • Groene Hart Ziekenhuis
      • Groningen, Netherlands, 9700 RM
        • Martini Ziekenhuis
      • Leiderdorp, Netherlands
        • Rijnland Ziekenhuis
      • Nijmegen, Netherlands, 6500 HB
        • University Medical Center St Radboud
      • Roosendaal, Netherlands, 4700 AZ
        • Franciscus Ziekenhuis
      • Rotterdam, Netherlands, 3045 PM
        • Sint Franciscus Gasthuis
      • Rotterdam, Netherlands, 3075 EA
        • Medisch Centrum Rijnmond Zuid - locatie Clara
      • Sittard, Netherlands, 6130 MB
        • Orbis Medisch en Zorgcentrum
      • Terneuzen, Netherlands, 4535 PA
        • Ziekenhuis Zeeuws-Vlaanderen
      • Tilburg, Netherlands, 5000 LC
        • St Elisabeth Ziekenhuis
      • Utrecht, Netherlands, 3584 CX
        • University Medical Center Utrecht
      • Utrecht, Netherlands, 3524 BN
        • Stichting Dianet
      • Venlo, Netherlands, 5912 BL
        • VieCuri Medisch Centrum
      • Zwolle, Netherlands, 8000 GM
        • Isala Klinieken
  • Norway
      • Bergen, Norway, 5021
        • Haukeland Universitetssykehus

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: 1: low flux hemodialysis
standard treatment
Procedure: low flux hemodialysis
standard treatment
Active Comparator: 2 on-line hemodiafiltration
Procedure: on-line hemodiafiltration
addition of convective transport to regular dialysis treatment by using on-line hemodiafiltration

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
all cause mortality
Time Frame: entire follow up (until dead or end of study, 1-7 years)
entire follow up (until dead or end of study, 1-7 years)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
fatal and non-fatal cardiovascular events
Time Frame: entire follow up (until death or end of study, 1-7 years)
entire follow up (until death or end of study, 1-7 years)
Left ventricular mass index (LVMi), carotid IMT (intima media thickness), aortic pulse wave velocity (PWV)
Time Frame: first 3 years
first 3 years
laboratory markers of endothelial dysfunction, micro-inflammation, oxidative stress
Time Frame: first three years of follow up
first three years of follow up
lipid profiles, uremic toxins
Time Frame: first three years
first three years
quality of life
Time Frame: entire follow up (until death or end of study, 1-7 years)
entire follow up (until death or end of study, 1-7 years)
nutritional state
Time Frame: entire follow up (until death or end of study 1-7 years)
entire follow up (until death or end of study 1-7 years)
anemia management
Time Frame: first 12 months of follow up
hemoglobin levels, erythropoietin use / resistance iron saturation / ferritin levels, prescription of iron medication
first 12 months of follow up
cost utility analysis
Time Frame: entire follow up (until death or end of study, 1-7 years)
entire follow up (until death or end of study, 1-7 years)
hospital admissions
Time Frame: entire follow up (until death or end of study, 1-7 years)
hospitalization days hospital admission for infections hospital admission for any cause
entire follow up (until death or end of study, 1-7 years)
blood pressure and antihypertensive medication
Time Frame: entire follow up (until death or end of study, 1-7 years)
entire follow up (until death or end of study, 1-7 years)
residual kidney function
Time Frame: entire follow up (until death or end of study, 1-7 years)
entire follow up (until death or end of study, 1-7 years)
mineral bone disease
Time Frame: entire follow up (until death or end of study, 1-7 years)
laboratory parameters of mineral bone disease and medication (phosphate binders, vitamin D (or analogues), cinacalet)
entire follow up (until death or end of study, 1-7 years)
parameters of treatment / treatment delivery
Time Frame: entire follow up (until death or end of study, 1-7 years)
dialysis efficiency (Kt/V urea); bloodflow, dialysate flow, ultrafiltration volume, (HDF:) convection volume
entire follow up (until death or end of study, 1-7 years)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Amsterdam UMC, location VUmc

Collaborators

Roche Pharma AG
Baxter Healthcare Corporation
UMC Utrecht
Fresenius Medical Care North America
Maasstad Hospital
Medical Center Alkmaar
Gambro Renal Products, Inc.
Dutch Kidney Foundation
Julius Center for Health Sciences and Primary Care, Utrecht

Investigators

  • 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2004

Primary Completion (Actual)

December 1, 2010

Study Completion (Actual)

January 1, 2011

Study Registration Dates

First Submitted

September 12, 2005

First Submitted That Met QC Criteria

September 12, 2005

First Posted (Estimate)

September 20, 2005

Study Record Updates

Last Update Posted (Estimate)

January 21, 2011

Last Update Submitted That Met QC Criteria

January 20, 2011

Last Verified

January 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • METC VUmc 03/097
  • ISRCTN38365125
  • CCMO number P03.1089L
  • Dutch Kidney Found C 02.2019

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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