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

NCT ID: NCT00205556

Last Updated: 2011-01-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

715 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-06-30

Study Completion Date

2011-01-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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End-stage Renal Disease Cardiovascular Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1: low flux hemodialysis

standard treatment

Group Type OTHER

low flux hemodialysis

Intervention Type PROCEDURE

standard treatment

2 on-line hemodiafiltration

Group Type ACTIVE_COMPARATOR

on-line hemodiafiltration

Intervention Type PROCEDURE

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

Interventions

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on-line hemodiafiltration

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

Intervention Type PROCEDURE

low flux hemodialysis

standard treatment

Intervention Type PROCEDURE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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UMC Utrecht

OTHER

Sponsor Role collaborator

Medical Center Alkmaar

OTHER

Sponsor Role collaborator

Maasstad Hospital

OTHER

Sponsor Role collaborator

Julius Center for Health Sciences and Primary Care, Utrecht

UNKNOWN

Sponsor Role collaborator

Dutch Kidney Foundation

OTHER

Sponsor Role collaborator

Fresenius Medical Care North America

INDUSTRY

Sponsor Role collaborator

Gambro Renal Products, Inc.

INDUSTRY

Sponsor Role collaborator

Baxter Healthcare Corporation

INDUSTRY

Sponsor Role collaborator

Roche Pharma AG

INDUSTRY

Sponsor Role collaborator

Amsterdam UMC, location VUmc

OTHER

Sponsor Role lead

Responsible Party

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Vrije Universiteit Medical Center and University Medical Center Utrecht

Principal Investigators

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Menso J Nubé, MD PhD

Role: STUDY_DIRECTOR

Medical Center Alkmaar

Piet M ter Wee, MD PhD

Role: STUDY_CHAIR

Vrije Universiteit Medical Center, Amsterdam

Peter J Blankestijn, MD PhD

Role: STUDY_CHAIR

Universityr Medical Center Utrecht

René A van den Dorpel, MD PhD

Role: STUDY_DIRECTOR

Medisch Centrum Rijnmond Zuid - locatie Clara, Rotterdam

Michiel L Bots, MD PhD

Role: STUDY_DIRECTOR

Julius Center for Health Sciences and Primary Care, Utrecht

Muriel PC Grooteman, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Vrije Universiteit Medical Center, Amsterdam

Locations

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Dr Georges-L. Dumont Regional Hospital

Moncton, New Brunswick, Canada

Site Status

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

Montreal, , Canada

Site Status

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, , Netherlands

Site Status

Medisch Centrum Alkmaar

Alkmaar, , Netherlands

Site Status

Vrije Universiteit Medisch Centrum

Amsterdam, , Netherlands

Site Status

Onze Lieve Vrouwe Gasthuis

Amsterdam, , Netherlands

Site Status

Academical Medical Center

Amsterdam, , Netherlands

Site Status

Ziekenhuis Rijnstate

Arnhem, , Netherlands

Site Status

Dialyse Kliniek Noord

Beilen, , Netherlands

Site Status

Slingeland Ziekenhuis

Doetinchem, , Netherlands

Site Status

Ziekenhuis Gelderse Vallei

Ede, , Netherlands

Site Status

Catharina Ziekenhuis

Eindhoven, , Netherlands

Site Status

Oosterscheldeziekenhuis

Goes, , Netherlands

Site Status

Groene Hart Ziekenhuis

Gouda, , Netherlands

Site Status

Martini Ziekenhuis

Groningen, , Netherlands

Site Status

Rijnland Ziekenhuis

Leiderdorp, , Netherlands

Site Status

University Medical Center St Radboud

Nijmegen, , Netherlands

Site Status

Franciscus Ziekenhuis

Roosendaal, , Netherlands

Site Status

Sint Franciscus Gasthuis

Rotterdam, , Netherlands

Site Status

Medisch Centrum Rijnmond Zuid - locatie Clara

Rotterdam, , Netherlands

Site Status

Orbis Medisch en Zorgcentrum

Sittard, , Netherlands

Site Status

Ziekenhuis Zeeuws-Vlaanderen

Terneuzen, , Netherlands

Site Status

Haga Ziekenhuis (locatie Leyenburg)

The Hague, , Netherlands

Site Status

St Elisabeth Ziekenhuis

Tilburg, , Netherlands

Site Status

Stichting Dianet

Utrecht, , Netherlands

Site Status

University Medical Center Utrecht

Utrecht, , Netherlands

Site Status

VieCuri Medisch Centrum

Venlo, , Netherlands

Site Status

Isala Klinieken

Zwolle, , Netherlands

Site Status

Haukeland Universitetssykehus

Bergen, , Norway

Site Status

Countries

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Canada Netherlands Norway

References

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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.

Reference Type BACKGROUND
PMID: 19231743 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15907201 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15663765 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16886698 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18045819 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19596741 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19606080 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20938124 (View on PubMed)

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.

Reference Type RESULT
PMID: 19515802 (View on PubMed)

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.

Reference Type RESULT
PMID: 19962805 (View on PubMed)

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.

Reference Type RESULT
PMID: 21194971 (View on PubMed)

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.

Reference Type RESULT
PMID: 21030579 (View on PubMed)

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.

Reference Type RESULT
PMID: 19965537 (View on PubMed)

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.

Reference Type RESULT
PMID: 20947533 (View on PubMed)

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.

Reference Type RESULT
PMID: 21051503 (View on PubMed)

de Roij van Zuijdewijn CL, Ter Wee PM. Assessment of Protein-Energy Wasting: Quest for the Gold Standard. J Ren Nutr. 2016 May;26(3):204-5. doi: 10.1053/j.jrn.2016.01.012. Epub 2016 Feb 20. No abstract available.

Reference Type DERIVED
PMID: 26908190 (View on PubMed)

de Roij van Zuijdewijn CL, Grooteman MP, Bots ML, Blankestijn PJ, Steppan S, Buchel J, Groenwold RH, Brandenburg V, van den Dorpel MA, Ter Wee PM, Nube MJ, Vervloet MG. Serum Magnesium and Sudden Death in European Hemodialysis Patients. PLoS One. 2015 Nov 23;10(11):e0143104. doi: 10.1371/journal.pone.0143104. eCollection 2015.

Reference Type DERIVED
PMID: 26600017 (View on PubMed)

de Roij van Zuijdewijn CL, Grooteman MP, Bots ML, Blankestijn PJ, van den Dorpel MA, Nube MJ, ter Wee PM. Comparing Tests Assessing Protein-Energy Wasting: Relation With Quality of Life. J Ren Nutr. 2016 Mar;26(2):111-7. doi: 10.1053/j.jrn.2015.09.003. Epub 2015 Oct 23.

Reference Type DERIVED
PMID: 26584787 (View on PubMed)

den Hoedt CH, Grooteman MP, Bots ML, Blankestijn PJ, van der Tweel I, van der Weerd NC, Penne EL, Mazairac AH, Levesque R, ter Wee PM, Nube MJ, van den Dorpel MA; CONTRAST investigators. The Effect of Online Hemodiafiltration on Infections: Results from the CONvective TRAnsport STudy. PLoS One. 2015 Aug 19;10(8):e0135908. doi: 10.1371/journal.pone.0135908. eCollection 2015.

Reference Type DERIVED
PMID: 26288091 (View on PubMed)

van der Weerd NC, Den Hoedt CH, Blankestijn PJ, Bots ML, van den Dorpel MA, Levesque R, Mazairac AH, Nube MJ, Penne EL, ter Wee PM, Grooteman MP; CONTRAST Investigators. Resistance to erythropoiesis stimulating agents in patients treated with online hemodiafiltration and ultrapure low-flux hemodialysis: results from a randomized controlled trial (CONTRAST). PLoS One. 2014 Apr 17;9(4):e94434. doi: 10.1371/journal.pone.0094434. eCollection 2014.

Reference Type DERIVED
PMID: 24743493 (View on PubMed)

van der Weerd NC, Grooteman MP, Blankestijn PJ, Mazairac AH, van den Dorpel MA, den Hoedt CH, Nube MJ, Penne EL, van der Tweel I, Ter Wee PM, Bots ML; CONTRAST investigators. Poor compliance with guidelines on anemia treatment in a cohort of chronic hemodialysis patients. Blood Purif. 2012;34(1):19-27. doi: 10.1159/000338919. Epub 2012 Aug 8.

Reference Type DERIVED
PMID: 22889943 (View on PubMed)

Other Identifiers

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ISRCTN38365125

Identifier Type: -

Identifier Source: secondary_id

CCMO number P03.1089L

Identifier Type: -

Identifier Source: secondary_id

Dutch Kidney Found C 02.2019

Identifier Type: -

Identifier Source: secondary_id

METC VUmc 03/097

Identifier Type: -

Identifier Source: org_study_id

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