Fixed Dose MMF vs Concentration Controlled MMF After Renal Transplantation

NCT00166244 | Completed Phase 4 DMC

• 1 other identifier: FDCC
• Study Type: interventional
• Target: 901
• Locations: 17 countries
• Sites: 51

Brief 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.

Conditions

De Novo Renal Transplant Recipient.

Keywords

Mycophenolate mofetil; Therapeutic Drug Monitoring; Adult kidney transplantation; Paediatric kidney transplantation

Outcome Measures

Primary Outcomes (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.

  12 Months

Secondary Outcomes (8)

• Proportion of patients treated for acute rejection during the first 3, 6, 12 months post-transplantation,

  3, 6 and 12 Months

• Time to first acute rejection,

  12 Months

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

  12 Months

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

  12 Months

• Graft loss,

  12 Months

Study Arms (2)

Fixed Dose

ACTIVE COMPARATOR

1 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.

Drug: Mycophenolate Mofetil

Concentration Controlled

ACTIVE COMPARATOR

1 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.

Drug: Mycophenolate Mofetil

Interventions

Mycophenolate Mofetil DRUG

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.

Also known as: CellCept

Concentration Controlled; Fixed Dose

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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,
• 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).

Sponsors & Collaborators

• Erasmus Medical Center: lead
• Hoffmann-La Roche: collaborator

Study Sites (67)

John Hunter Hospital

New Lambton, New South Wales, 2305, Australia

Location

Princess Alexandra Hospital

Brisbane, Queensland, 4102, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

St Vincent's Hospital

Melbourne, Victoria, 3065, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, 3052, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6847, Australia

Location

Med. Univ. Klinik

Graz, 8036, Austria

Location

AKH Wien

Vienna, Vienna, Austria

Location

University Hospitals Leuven

Leuven, 3000, Belgium

Location

Hospital do Rim e Hipertensao

São Paulo, CEP 0438-002, Brazil

Location

Vancouver General Hospital

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Ruijin Hospital

Shanghai, Shanghai Municipality, 200001, China

Location

West China Hospital of Sichuan University

Chengdu, Sichuan, China

Location

Odense University Hospital

Odense, 5000, Denmark

Location

Surgical Clinic Of Tartu University Clinics

Tartu, 51014, Estonia

Location

Hopital Pellegrin, C.H.R.de Bordeaux

Bordeaux, 33076, France

Location

Hospital du Bocage

Dijon, 21000, France

Location

CHU de Grenoble

Grenoble, 38043, France

Location

CHU Kremlin Bicêtre

Le Kremlin-Bicêtre, 94275, France

Location

Hopital Calmette

Lille, 59037, France

Location

Hopital Jeanne de Flandres

Lille, 59037, France

Location

Centre Hospitalier Regional Universitaire

Limoges, 87042, France

Location

CHU Hotel Dieu

Nantes, 44093, France

Location

Hopital Necker

Paris, 75015, France

Location

Hopital Tenon

Paris, 75020, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Hopital Foch

Suresnes, 92151, France

Location

CHU Purpan

Toulouse, 31059, France

Location

CHU Rangueil

Toulouse, 31059, France

Location

CHU de Nancy-Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

Universitatsklinikum Charite

Berlin, 10098, Germany

Location

Stadt Kliniken Koln

Cologne, 51009, Germany

Location

Chirurgische Universitätsklinik

Freiburg im Breisgau, 79106, Germany

Location

Universitatsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

University of Heidelberg

Heidelberg, 69120, Germany

Location

University Hospital Wurzburg

Würzburg, 97080, Germany

Location

Vilnius University Hospital

Vilnius, 2021, Lithuania

Location

Leids Universitair Medisch Centrum

Leiden, 2333, Netherlands

Location

Erasmus Medical Center Rotterdam

Rotterdam, 3000, Netherlands

Location

Rikshopitalet

Oslo, 0027, Norway

Location

Institute of Transplantology, Medical University of Warsaw

Warsaw, 02-006, Poland

Location

Children's Memorial Health Institute

Warsaw, 04-736, Poland

Location

Hospital Son Dureta

Palma de Mallorca, 07014, Spain

Location

Hospital Infanta Christa

Badajoz, 06080, Spain

Location

Hospital Del Mar

Barcelona, 08003, Spain

Location

Valle de Hebron

Barcelona, 08035, Spain

Location

Hospital Sant Joan de Deu

Barcelona, 8950, Spain

Location

Hospital Reina Sofia

Córdoba, 14004, Spain

Location

Hospital de las Nieves

Granada, 18014, Spain

Location

Hospital Ramon Y Cajal

Madrid, 28034, Spain

Location

Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

La Paz

Madrid, 28046, Spain

Location

Complejo Hospitalario Univeritario de Santiago

Santiago de Compostela, 15706, Spain

Location

Hospital Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Dr. Peset

Valencia, Spain

Location

University Hospital, Malmo

Malmo, 205 02, Sweden

Location

Karolinska University Hospital, Huddinge

Stockholm, 141 86, Sweden

Location

University Hospital A

Uppsala, 751 85, Sweden

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Guys and St Thomas's Hospital

London, SE1 9RT, United Kingdom

Location

St George's Hospital

London, SW17 ORE, United Kingdom

Location

Hospital "Miguel Perez Carreno"

Caracas, Venezuela

Location

Hospital Universitario de Caracas

Caracas, Venezuela

Location

Hospital Universitario de Maracaibo

Maracaibo, Venezuela

Location

Related Publications (5)

• 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.

  PMID: 10440399 BACKGROUND

• 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.

  PMID: 18946341 RESULT

• 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.

  PMID: 20670958 DERIVED

• 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.

  PMID: 20124953 DERIVED

• 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.

  PMID: 19494809 DERIVED

MeSH Terms

Interventions

Mycophenolic Acid

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

Study Officials

• Teun van Gelder, Dr

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 9, 2005
• First Posted: September 14, 2005
• Study Start: May 1, 2003
• Primary Completion: March 1, 2005
• Study Completion: April 1, 2006
• Last Updated: February 12, 2009

Record last verified: 2009-02

Locations

LI (1); NO (1); FR (15); ES (1); CA (1); AU (7); DE (6); CN (2); DK (1); BE (1); SE (3); NL (2); PL (2); GB (3); VE (3); BR (1); TW (1)