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
  Purpose

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.


Condition Intervention
End-stage Renal Disease
Cardiovascular Disease
Procedure: on-line hemodiafiltration
Procedure: low flux hemodialysis

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by VU University Medical Center:

Primary Outcome Measures:
  • all cause mortality [ Time Frame: entire follow up (until dead or end of study, 1-7 years) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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


Enrollment: 715
Study Start Date: June 2004
Study Completion Date: January 2011
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00205556

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

Additional Information:
Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: contact person: MPC Grooteman MD PhD, Vrije Universiteit Medical Center and University Medical Center Utrecht
ClinicalTrials.gov Identifier: NCT00205556     History of Changes
Other Study ID Numbers: METC VUmc 03/097, ISRCTN38365125, CCMO number P03.1089L, Dutch Kidney Found C 02.2019
Study First Received: September 12, 2005
Last Updated: January 20, 2011
Health Authority: Netherlands: Dutch Health Care Inspectorate

Keywords provided by VU University Medical Center:
online hemodiafiltration
low flux hemodialysis
cardiovascular disease
endothelial dysfunction
uremic toxicity
quality of life
nutritional status

Additional relevant MeSH terms:
Cardiovascular Diseases
Kidney Diseases
Kidney Failure, Chronic
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency

ClinicalTrials.gov processed this record on August 28, 2014