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End-stage Renal DiseaseCONTRASTNCT00205556

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

A study testing on-line hemodiafiltration and low flux hemodialysis in people with End-stage Renal Disease and Cardiovascular Disease, run by Amsterdam UMC, location VUmc at 29 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
on-line hemodiafiltration and low flux hemodialysis
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
715 participants
Where
29 sitesin 3 countries
Study dates
Jun 2004to Jan 2011
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

29 sites in 3 countries.

29 sites in 3 countries

Netherlands26 sites

  • Jeroen Bosch Ziekenhuis

    's-Hertogenbosch, 5200 ME

  • Medisch Centrum Alkmaar

    Alkmaar, 1815 JD

  • Vrije Universiteit Medisch Centrum

    Amsterdam, 1081 HV

  • Onze Lieve Vrouwe Gasthuis

    Amsterdam, 1090 HM

  • Academical Medical Center

    Amsterdam, 1100 DD

  • Ziekenhuis Rijnstate

    Arnhem, 6800 TA

  • Dialyse Kliniek Noord

    Beilen, 9411 SE

  • Slingeland Ziekenhuis

    Doetinchem, 7009 BL

  • Ziekenhuis Gelderse Vallei

    Ede, 6710 HN

  • Catharina Ziekenhuis

    Eindhoven, 5602 ZA

  • Oosterscheldeziekenhuis

    Goes, 4460 BB

  • Groene Hart Ziekenhuis

    Gouda

  • Martini Ziekenhuis

    Groningen, 9700 RM

  • Rijnland Ziekenhuis

    Leiderdorp

  • University Medical Center St Radboud

    Nijmegen, 6500 HB

  • Franciscus Ziekenhuis

    Roosendaal, 4700 AZ

  • Sint Franciscus Gasthuis

    Rotterdam, 3045 PM

  • Medisch Centrum Rijnmond Zuid - locatie Clara

    Rotterdam, 3075 EA

  • Orbis Medisch en Zorgcentrum

    Sittard, 6130 MB

  • Ziekenhuis Zeeuws-Vlaanderen

    Terneuzen, 4535 PA

  • Haga Ziekenhuis (locatie Leyenburg)

    The Hague, 2545 CH

  • St Elisabeth Ziekenhuis

    Tilburg, 5000 LC

  • Stichting Dianet

    Utrecht, 3524 BN

  • University Medical Center Utrecht

    Utrecht, 3584 CX

  • VieCuri Medisch Centrum

    Venlo, 5912 BL

  • Isala Klinieken

    Zwolle, 8000 GM

Other trials in Netherlands

Canada2 sites

  • Dr Georges-L. Dumont Regional Hospital

    Moncton, New Brunswick

  • Centre Hospitalier de L'Université de Montreal, Hopital Notre Dame

    Montreal, H2L 4M1

Other trials in Canada

Norway1 site

  • Haukeland Universitetssykehus

    Bergen, 5021

Other trials in Norway

About this study

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)

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.

Read the 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.
Being tested
on-line hemodiafiltration, low flux hemodialysis
Keywords
online hemodiafiltration, low flux hemodialysis, cardiovascular disease, endothelial dysfunction, uremic toxicity, quality of life, nutritional status
Medical subject headings
Kidney Failure, Chronic, Cardiovascular Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • on-line hemodiafiltrationProcedure or surgery

    addition of convective transport to regular dialysis treatment by using on-line hemodiafiltration

  • low flux hemodialysisProcedure or surgery

    standard treatment

Study groups in NCT00205556
Study groupRoleWhat they receive
1: low flux hemodialysisOtherstandard treatment
Receives: Procedure: low flux hemodialysis
2 on-line hemodiafiltrationActive comparatorNot described
Receives: Procedure: on-line hemodiafiltration

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. all cause mortality

    Measured: entire follow up (until dead or end of study, 1-7 years)

Secondary outcomes (13)

  1. fatal and non-fatal cardiovascular events

    Measured: entire follow up (until death or end of study, 1-7 years)

  2. Left ventricular mass index (LVMi), carotid IMT (intima media thickness), aortic pulse wave velocity (PWV)

    Measured: first 3 years

  3. laboratory markers of endothelial dysfunction, micro-inflammation, oxidative stress

    Measured: first three years of follow up

  4. lipid profiles, uremic toxins

    Measured: first three years

  5. quality of life

    Measured: entire follow up (until death or end of study, 1-7 years)

  6. nutritional state

    Measured: entire follow up (until death or end of study 1-7 years)

  7. anemia management

    hemoglobin levels, erythropoietin use / resistance iron saturation / ferritin levels, prescription of iron medication

    Measured: first 12 months of follow up

  8. cost utility analysis

    Measured: entire follow up (until death or end of study, 1-7 years)

  9. hospital admissions

    hospitalization days hospital admission for infections hospital admission for any cause

    Measured: entire follow up (until death or end of study, 1-7 years)

  10. blood pressure and antihypertensive medication

    Measured: entire follow up (until death or end of study, 1-7 years)

  11. residual kidney function

    Measured: entire follow up (until death or end of study, 1-7 years)

  12. mineral bone disease

    laboratory parameters of mineral bone disease and medication (phosphate binders, vitamin D (or analogues), cinacalet)

    Measured: entire follow up (until death or end of study, 1-7 years)

  13. parameters of treatment / treatment delivery

    dialysis efficiency (Kt/V urea); bloodflow, dialysate flow, ultrafiltration volume, (HDF:) convection volume

    Measured: entire follow up (until death or end of study, 1-7 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Sep 2005 (estimated)
  2. Study startJun 2004
  3. Primary completionDec 2010
  4. Study completionJan 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
715 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00205556
Sponsor's protocol ID
METC VUmc 03/097
Other IDs
ISRCTN38365125, CCMO number P03.1089L, Dutch Kidney Found C 02.2019
Acronym
CONTRAST
Status last verified
Jan 2011
First submitted
12 Sep 2005
Last updated
21 Jan 2011
Results posted
No
Data monitoring committee
Yes

Publications

  • Penne EL, Blankestijn PJ, Bots ML, van den Dorpel MA, Grooteman MP, Nube MJ, van der Tweel I, Ter Wee PM; the CONTRAST study group. 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): rationale and design of a randomised controlled trial [ISRCTN38365125]. Curr Control Trials Cardiovasc Med. 2005 May 20;6(1):8. doi: 10.1186/1468-6708-6-8.

    PubMed 15907201

  • Penne EL, Blankestijn PJ, Bots ML, van den Dorpel MA, Grooteman MP, Nube MJ, ter Wee PM; CONTRAST Group. Resolving controversies regarding hemodiafiltration versus hemodialysis: the Dutch Convective Transport Study. Semin Dial. 2005 Jan-Feb;18(1):47-51. doi: 10.1111/j.1525-139X.2005.18107.x.

    PubMed 15663765

  • Penne EL, Blankestijn PJ, Bots ML, van den Dorpel MA, Grooteman MP, Nube MJ, ter Wee PM. [New study evaluating online haemodiafiltration for the reduction of cardiovascular morbidity and mortality in patients undergoing chronic haemodialysis]. Ned Tijdschr Geneeskd. 2006 Jul 15;150(28):1583-5. Dutch.

    PubMed 16886698

  • van der Weerd NC, Penne EL, van den Dorpel MA, Grooteman MP, Nube MJ, Bots ML, ter Wee PM, Blankestijn PJ. Haemodiafiltration: promise for the future? Nephrol Dial Transplant. 2008 Feb;23(2):438-43. doi: 10.1093/ndt/gfm791. Epub 2007 Nov 28. No abstract available.

    PubMed 18045819

  • Penne EL, van Berkel T, van der Weerd NC, Grooteman MP, Blankestijn PJ. Optimizing haemodiafiltration: tools, strategy and remaining questions. Nephrol Dial Transplant. 2009 Dec;24(12):3579-81. doi: 10.1093/ndt/gfp333. Epub 2009 Jul 13. No abstract available.

    PubMed 19596741

  • van der Weerd NC, Penne EL, Grooteman MP. Effect of hemofiltration on mortality: no definite answer yet. Am J Kidney Dis. 2009 Mar;53(3):562-3; author reply 563. doi: 10.1053/j.ajkd.2008.09.029. No abstract available.

    PubMed 19231743

  • Penne EL, Visser L, van den Dorpel MA, van der Weerd NC, Mazairac AH, van Jaarsveld BC, Koopman MG, Vos P, Feith GW, Kremer Hovinga TK, van Hamersvelt HW, Wauters IM, Bots ML, Nube MJ, Ter Wee PM, Blankestijn PJ, Grooteman MP. Microbiological quality and quality control of purified water and ultrapure dialysis fluids for online hemodiafiltration in routine clinical practice. Kidney Int. 2009 Sep;76(6):665-72. doi: 10.1038/ki.2009.245. Epub 2009 Jul 15.

    PubMed 19606080

  • den Hoedt CH, Mazairac AHA, van den Dorpel MA, Grooteman MPC, Blankestijn PJ. Effect of hemodiafiltration on mortality, inflammation and quality of life. Contrib Nephrol. 2011;168:39-52. doi: 10.1159/000321743. Epub 2010 Oct 7.

    PubMed 20938124

  • Penne EL, van der Weerd NC, Bots ML, van den Dorpel MA, Grooteman MP, Levesque R, Nube MJ, Ter Wee PM, Blankestijn PJ; CONTRAST investigators. Patient- and treatment-related determinants of convective volume in post-dilution haemodiafiltration in clinical practice. Nephrol Dial Transplant. 2009 Nov;24(11):3493-9. doi: 10.1093/ndt/gfp265. Epub 2009 Jun 10.

    PubMed 19515802

  • Penne EL, van der Weerd NC, van den Dorpel MA, Grooteman MP, Levesque R, Nube MJ, Bots ML, Blankestijn PJ, ter Wee PM; CONTRAST Investigators. Short-term effects of online hemodiafiltration on phosphate control: a result from the randomized controlled Convective Transport Study (CONTRAST). Am J Kidney Dis. 2010 Jan;55(1):77-87. doi: 10.1053/j.ajkd.2009.09.023. Epub 2009 Dec 5.

    PubMed 19962805

  • Mazairac AH, de Wit GA, Penne EL, van der Weerd NC, Grooteman MP, van den Dorpel MA, Nube MJ, Buskens E, Levesque R, Ter Wee PM, Bots ML, Blankestijn PJ; CONTRAST investigators. Protein-energy nutritional status and kidney disease-specific quality of life in hemodialysis patients. J Ren Nutr. 2011 Sep;21(5):376-386.e1. doi: 10.1053/j.jrn.2010.08.004. Epub 2010 Dec 30.

    PubMed 21194971

  • Penne EL, van der Weerd NC, Grooteman MP, Mazairac AH, van den Dorpel MA, Nube MJ, Bots ML, Levesque R, ter Wee PM, Blankestijn PJ; CONTRAST investigators. Role of residual renal function in phosphate control and anemia management in chronic hemodialysis patients. Clin J Am Soc Nephrol. 2011 Feb;6(2):281-9. doi: 10.2215/CJN.04480510. Epub 2010 Oct 28.

    PubMed 21030579

  • Penne EL, van der Weerd NC, Blankestijn PJ, van den Dorpel MA, Grooteman MP, Nube MJ, Ter Wee PM, Levesque R, Bots ML; CONTRAST investigators. Role of residual kidney function and convective volume on change in beta2-microglobulin levels in hemodiafiltration patients. Clin J Am Soc Nephrol. 2010 Jan;5(1):80-6. doi: 10.2215/CJN.03340509. Epub 2009 Nov 12.

    PubMed 19965537

  • Mazairac AH, de Wit GA, Grooteman MP, Penne EL, van der Weerd NC, van den Dorpel MA, Nube MJ, Levesque R, Ter Wee PM, Bots ML, Blankestijn PJ; CONTRAST investigators. A composite score of protein-energy nutritional status predicts mortality in haemodialysis patients no better than its individual components. Nephrol Dial Transplant. 2011 Jun;26(6):1962-7. doi: 10.1093/ndt/gfq643. Epub 2010 Oct 14.

    PubMed 20947533

  • Mazairac AH, de Wit GA, Penne EL, van der Weerd NC, de Jong B, Grooteman MP, van den Dorpel MA, Buskens E, Dekker FW, Nube MJ, Ter Wee PM, Boeschoten EW, Bots ML, Blankestijn PJ; CONTRAST investigators. Changes in quality of life over time--Dutch haemodialysis patients and general population compared. Nephrol Dial Transplant. 2011 Jun;26(6):1984-9. doi: 10.1093/ndt/gfq680. Epub 2010 Nov 4.

    PubMed 21051503

Questions about this trial

What is this clinical trial studying?

A study testing on-line hemodiafiltration and low flux hemodialysis in people with End-stage Renal Disease and Cardiovascular Disease, run by Amsterdam UMC, location VUmc at 29 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Jan 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 29 sites in Netherlands, Canada, Norway. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

all cause mortality (time frame: entire follow up (until dead or end of study, 1-7 years)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00205556, which also lists 21 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jan 2011.

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