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De Novo Renal Transplant Recipient.Phase 4NCT00166244

Fixed Dose MMF vs Concentration Controlled MMF After Renal Transplantation

A Phase 4 study testing Mycophenolate Mofetil in people with De Novo Renal Transplant Recipient., run by Erasmus Medical Center at 67 sites in 19 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

Determine the value of a clinically feasible strategy of therapeutic drug monitoring compared with fixed dosing in de novo MMF treated renal transplant recipients with respect to the incidence of treatment failure. Read more about this study

Who is it for?
Ages 2 years and older
Conditions the study is for
De Novo Renal Transplant Recipient.
What is being tested?
Mycophenolate Mofetil
Could I receive a placebo?
No, everyone receives an active treatment
How many people
901 participants
Where
67 sitesin 19 countries
Study dates
May 2003to Apr 2006
Phase
Phase 4
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 2 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Renal transplant recipients who have completed their second birthday,
  • Recipients from living (related or unrelated), cadaveric (non-heart beating or heart beating) donors,
  • Single organ recipient (kidney only),
  • Women of childbearing potential should have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/ml within 1 week prior to beginning MMF treatment. Effective contraception must be used before beginning therapy, during therapy and for 6 weeks following discontinuation of therapy, even where there has been a history of infertility, unless due to hysterectomy,
  • Patients or patient's parent/guardian providing written informed consent,
  • Patients co-operative and able to complete all the assessment procedures.

Who cannot join

  • Patients receiving immunosuppressive therapy (except steroid treatment) within the preceding 28 days, except that immunosuppressive medication may be initiated up to 48 hours before transplantation. Furthermore, all patients should receive 1 g [adults] or 600 mg/m2 [paediatric patients] of MMF therapy within 6 hours prior to transplantation,
  • PRA > 50% within 6 months prior to enrolment,
  • Cold ischaemia time >48 hours,
  • History of malignancy (except localised non-melanotic skin cancer) or the presence of any active malignancy at the time of transplant,
  • Active peptic ulcer disease,
  • Active infection,
Show all 15Show fewer
  • Mandatory intake of prohibited drugs or it is probable that the patient will require treatment with such drugs after transplant,
  • Pregnant or lactating females,
  • Women of child-bearing potential not willing to use a reliable form of contraception,
  • Patient is allergic or intolerant to polysorbate 80 (TWEEN), phenylalanine (aspartame), steroids, MMF, MPA, tacrolimus or cyclosporin,
  • Patient or donor with positive tests for HIV or hepatitis B surface antigen,
  • Patients with liver cirrhosis or clinical evidence of portal hypertension or other indication of moderate or severe liver disease. (Note: it is strongly recommended that patients with hepatitis C have a liver biopsy performed prior to transplantation),
  • Incompatible ABO blood type and/or positive crossmatch,
  • Patient has any form of substance abuse, psychiatric disorder or condition, which, in the opinion of the investigator, may invalidate communication with the investigator or with study procedures,
  • Patients whose laboratory results reveal severe anaemia (as defined by a haemoglobin value <6 mmol/L [9.7 g/dL] for adults receiving erythropoietin, <4.1 mmol/L [6.6 g/dL] for paediatric patients [regardless of erythropoietin treatment]), leukopenia (as defined by a WBC value of <2500/mm3) or thrombocytopenia (as defined by a platelet count of <75,000/mm3).

Trial locations and contacts

67 sites in 19 countries.

67 sites in 19 countries

France15 sites
  • Hopital Pellegrin, C.H.R.de Bordeaux

    Bordeaux, 33076

  • Hospital du Bocage

    Dijon, 21000

  • CHU de Grenoble

    Grenoble, 38043

  • CHU Kremlin Bicêtre

    Le Kremlin-Bicêtre, 94275

  • Hopital Calmette

    Lille, 59037

  • Hopital Jeanne de Flandres

    Lille, 59037

  • Centre Hospitalier Regional Universitaire

    Limoges, 87042

  • CHU Hotel Dieu

    Nantes, 44093

  • Hopital Necker

    Paris, 75015

  • Hopital Tenon

    Paris, 75020

  • Centre Hospitalier Lyon Sud

    Pierre-Bénite, 69495

  • Hopital Foch

    Suresnes, 92151

  • CHU Purpan

    Toulouse, 31059

  • CHU Rangueil

    Toulouse, 31059

  • CHU de Nancy-Brabois

    Vandœuvre-lès-Nancy, 54511

Other trials in France

Spain14 sites
  • Hospital Infanta Christa

    Badajoz, 06080

  • Hospital Del Mar

    Barcelona, 08003

  • Valle de Hebron

    Barcelona, 08035

  • Hospital Sant Joan de Deu

    Barcelona, 8950

  • Hospital Reina Sofia

    Córdoba, 14004

  • Hospital de las Nieves

    Granada, 18014

  • Hospital Ramon Y Cajal

    Madrid, 28034

  • Fundacion Jimenez Diaz

    Madrid, 28040

  • Hospital Clinico San Carlos

    Madrid, 28040

  • La Paz

    Madrid, 28046

  • Hospital Son Dureta

    Palma de Mallorca, 07014

  • Complejo Hospitalario Univeritario de Santiago

    Santiago de Compostela, 15706

  • Hospital Virgen del Rocio

    Seville, 41013

  • Hospital Dr. Peset

    Valencia

Other trials in Spain

Australia7 sites
  • Princess Alexandra Hospital

    Brisbane, Queensland, 4102

  • Monash Medical Centre

    Clayton, Victoria, 3168

  • St Vincent's Hospital

    Melbourne, Victoria, 3065

  • Sir Charles Gairdner Hospital

    Nedlands, Western Australia, 6009

  • John Hunter Hospital

    New Lambton, New South Wales, 2305

  • Royal Melbourne Hospital

    Parkville, Victoria, 3052

  • Royal Perth Hospital

    Perth, Western Australia, 6847

Other trials in Australia

Germany6 sites
  • Universitatsklinikum Charite

    Berlin, 10098

  • Stadt Kliniken Koln

    Cologne, 51009

  • Chirurgische Universitätsklinik

    Freiburg im Breisgau, 79106

  • Universitatsklinikum Heidelberg

    Heidelberg, 69120

  • University of Heidelberg

    Heidelberg, 69120

  • University Hospital Wurzburg

    Würzburg, 97080

Other trials in Germany

Sweden3 sites
  • University Hospital, Malmo

    Malmö, 205 02

  • Karolinska University Hospital, Huddinge

    Stockholm, 141 86

  • University Hospital A

    Uppsala, 751 85

Other trials in Sweden

United Kingdom3 sites
  • Royal Free Hospital

    London, NW3 2QG

  • Guys and St Thomas's Hospital

    London, SE1 9RT

  • St George's Hospital

    London, SW17 ORE

Other trials in United Kingdom

Venezuela3 sites
  • Hospital "Miguel Perez Carreno"

    Caracas

  • Hospital Universitario de Caracas

    Caracas

  • Hospital Universitario de Maracaibo

    Maracaibo

Other trials in Venezuela

Austria2 sites
  • Med. Univ. Klinik

    Graz, 8036

  • AKH Wien

    Vienna, Vienna

Other trials in Austria

China2 sites
  • West China Hospital of Sichuan University

    Chengdu, Sichuan

  • Ruijin Hospital

    Shanghai, Shanghai Municipality, 200001

Other trials in China

Netherlands2 sites
  • Leids Universitair Medisch Centrum

    Leiden, 2333

  • Erasmus Medical Center Rotterdam

    Rotterdam, 3000

Other trials in Netherlands

Poland2 sites
  • Institute of Transplantology, Medical University of Warsaw

    Warsaw, 02-006

  • Children's Memorial Health Institute

    Warsaw, 04-736

Other trials in Poland

Belgium1 site
  • University Hospitals Leuven

    Leuven, 3000

Other trials in Belgium

Brazil1 site
  • Hospital do Rim e Hipertensao

    São Paulo, CEP 0438-002

Other trials in Brazil

Canada1 site
  • Vancouver General Hospital

    Vancouver, British Columbia, V5Z 1M9

Other trials in Canada

Denmark1 site
  • Odense University Hospital

    Odense, 5000

Other trials in Denmark

Estonia1 site
  • Surgical Clinic Of Tartu University Clinics

    Tartu, 51014

Other trials in Estonia

Lithuania1 site
  • Vilnius University Hospital

    Vilnius, 2021

Other trials in Lithuania

Norway1 site
  • Rikshopitalet

    Oslo, 0027

Other trials in Norway

Taiwan1 site
  • National Taiwan University Hospital

    Taipei

Other trials in Taiwan

About this study

Official title: An Open, Prospective, Randomised, Controlled, Multi-Center Study Comparing Fixed Dose vs Concentration Controlled Mycophenolate Mofetil Regimens for de Novo Patients Following Transplantation

Determine the value of a clinically feasible strategy of therapeutic drug monitoring compared with fixed dosing in de novo MMF treated renal transplant recipients with respect to the incidence of treatment failure.

Read the detailed description

For treatment with mycophenolate mofetil the contribution of TDM still has to be determined, although circumstantial evidence suggests the measurement of mycophenolic acid plasma concentrations adds to patient management.

A concerted effort to test the hypothesis that TDM will improve outcome in mycophenolate mofetil therapy in a prospective randomised trial is to be made if we want to have a solid base for the continued measurements of mycophenolic acid concentrations in the future. This trial aims to demonstrate the added value of TDM for mycophenolic acid, by comparing fixed dose treatment with concentration controlled mycophenolate mofetil treatment in kidney transplant recipients.

Keywords
Mycophenolate mofetil, Therapeutic Drug Monitoring, Adult kidney transplantation, Paediatric kidney transplantation

What participants receive

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

  • Mycophenolate MofetilDrug

    Also called CellCept

    1 g for adult patients and 300 mg/m2 for paediatric patients. Fixed dose arm: 1 g twice a day (bid) for adults and 600mg/m2 bid for paediatric patients.

    Concentration controlled arm: initial dose will be 1 g bid for adults and 600mg/m2 bid for paediatric patients. Abbreviated AUCs (taken at timepoints: 0, 30min and 120min in fasted patients) on Days 3 and 10, Week 4, Months 3, 6 and 12 will be performed to determine mycophenolic acid levels in plasma.

Study groups in NCT00166244
Study groupRoleWhat they receive
Fixed DoseActive comparator1 g MMF twice-daily (bid) for adults or 600 mg/m2 bid for paediatric patients. Treatment to be given orally unless it is not possible, in which case it is administered via intravenous (iv) infusion.
Receives: Drug: Mycophenolate Mofetil
Concentration ControlledActive comparator1 g MMF bid for adults or 600 mg/m2 bid for paediatric patients. Thereafter, MMF doses will be adjusted to MPA AUC0-12 between 30-60mg.h/L based on 3-point abbreviated AUCs (taken at timepoints: 0, 30 min and 120 min always in fasted patients, except for pediatric patients on concomitant tacrolimus) on Days 3 and 10, Week 4, Months 3, 6 and 12 will be performed to determine MPA levels in plasma.
Receives: Drug: Mycophenolate Mofetil

What is being measured

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

  1. Treatment failure including the occurrence of the first one of any of the following: biopsy-proven acute rejection, graft loss, death or discontinuation of MMF therapy during the first 12 months following transplantation.

    Measured: 12 Months

Secondary outcomes (8)
  1. Proportion of patients treated for acute rejection during the first 3, 6, 12 months post-transplantation,

    Measured: 3, 6 and 12 Months

  2. Time to first acute rejection,

    Measured: 12 Months

  3. Number of acute rejection episodes per patient in the first year post-transplantation,

    Measured: 12 Months

  4. Overall treatment outcome at 12 months post-transplantation which is composed of any one of the following:

    Measured: 12 Months

  5. Graft loss,

    Measured: 12 Months

  6. Death,

    Measured: 12 Months

  7. Discontinuation of MMF therapy,

    Measured: 12 Months

  8. Patient lost to follow-up.

    Measured: 12 Months

Timeline

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

  1. First posted14 Sep 2005 (estimated)
  2. Study startMay 2003
  3. Primary completionMar 2005
  4. Study completionApr 2006

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 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
901 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00166244
Sponsor's protocol ID
FDCC
Status last verified
Feb 2009
First submitted
9 Sep 2005
Last updated
12 Feb 2009
Results posted
No
Data monitoring committee
Yes

Publications

  • van Gelder T, Hilbrands LB, Vanrenterghem Y, Weimar W, de Fijter JW, Squifflet JP, Hene RJ, Verpooten GA, Navarro MT, Hale MD, Nicholls AJ. A randomized double-blind, multicenter plasma concentration controlled study of the safety and efficacy of oral mycophenolate mofetil for the prevention of acute rejection after kidney transplantation. Transplantation. 1999 Jul 27;68(2):261-6. doi: 10.1097/00007890-199907270-00018.

    PubMed 10440399
  • van Gelder T, Silva HT, de Fijter JW, Budde K, Kuypers D, Tyden G, Lohmus A, Sommerer C, Hartmann A, Le Meur Y, Oellerich M, Holt DW, Tonshoff B, Keown P, Campbell S, Mamelok RD. Comparing mycophenolate mofetil regimens for de novo renal transplant recipients: the fixed-dose concentration-controlled trial. Transplantation. 2008 Oct 27;86(8):1043-51. doi: 10.1097/TP.0b013e318186f98a.

    PubMed 18946341
  • Hocker B, van Gelder T, Martin-Govantes J, Machado P, Tedesco H, Rubik J, Dehennault M, Garcia Meseguer C, Tonshoff B; FDCC Study Group. Comparison of MMF efficacy and safety in paediatric vs. adult renal transplantation: subgroup analysis of the randomised, multicentre FDCC trial. Nephrol Dial Transplant. 2011 Mar;26(3):1073-9. doi: 10.1093/ndt/gfq450. Epub 2010 Jul 28.

    PubMed 20670958
  • van Gelder T, Tedesco Silva H, de Fijter JW, Budde K, Kuypers D, Arns W, Soulillou JP, Kanellis J, Zelvys A, Ekberg H, Holzer H, Rostaing L, Mamelok RD. Renal transplant patients at high risk of acute rejection benefit from adequate exposure to mycophenolic acid. Transplantation. 2010 Mar 15;89(5):595-9. doi: 10.1097/TP.0b013e3181ca7d84.

    PubMed 20124953
  • van Schaik RH, van Agteren M, de Fijter JW, Hartmann A, Schmidt J, Budde K, Kuypers D, Le Meur Y, van der Werf M, Mamelok R, van Gelder T. UGT1A9 -275T>A/-2152C>T polymorphisms correlate with low MPA exposure and acute rejection in MMF/tacrolimus-treated kidney transplant patients. Clin Pharmacol Ther. 2009 Sep;86(3):319-27. doi: 10.1038/clpt.2009.83. Epub 2009 Jun 3.

    PubMed 19494809

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Mycophenolate Mofetil in people with De Novo Renal Transplant Recipient., run by Erasmus Medical Center at 67 sites in 19 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 6 inclusion and 15 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 12 Feb 2009. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 67 sites in France, Spain, Australia, Germany, Sweden and 14 more countries. 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.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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?

Treatment failure including the occurrence of the first one of any of the following: biopsy-proven acute rejection, graft loss, death or discontinuation of MMF therapy during the first 12 months following transplantation. (time frame: 12 Months). 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 NCT00166244, which also lists 5 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 12 Feb 2009.

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