Fixed Dose MMF vs Concentration Controlled MMF After Renal Transplantation

Phase 4

Completed

• Conditions: De Novo Renal Transplant Recipient.
• Interventions: Drug: Mycophenolate Mofetil

• Registration Number: NCT00166244
• Lead Sponsor: Erasmus Medical Center

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.

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.

Study Timeline

• Study Start: 2003-05
• Primary Completion: 2005-03
• Study First Submitted: 2005-09-09
• Study First Submitted QC: 2005-09-09
• Study First Posted: 2005-09-14
• Study Completion: 2006-04
• Status Verified: 2009-02
• Last Update Submitted: 2009-02-11
• Last Update Posted: 2009-02-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 901

Inclusion Criteria

• 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.

Exclusion Criteria

• 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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fixed Dose	Mycophenolate Mofetil	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.
Concentration Controlled	Mycophenolate Mofetil	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Graft loss,	12 Months
Death,	12 Months
Discontinuation of MMF therapy,	12 Months
Patient lost to follow-up.	12 Months
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

Trial Locations

Locations (67)

University Hospitals Leuven; 🇧🇪 Leuven, Belgium

Vancouver General Hospital; 🇨🇦 Vancouver, British Columbia, Canada

Sir Charles Gairdner Hospital; 🇦🇺 Nedlands, Western Australia, Australia

Royal Perth Hospital; 🇦🇺 Perth, Western Australia, Australia

CHU Kremlin Bicêtre; 🇫🇷 Kremlin Bicêtre, France

Rikshopitalet; 🇳🇴 Oslo, Norway

Universitatsklinikum Charite; 🇩🇪 Berlin, Germany

Vilnius University Hospital; 🇱🇹 Vilnius, Lithuania

Hospital Del Mar; 🇪🇸 Barcelona, Spain

Hospital de las Nieves; 🇪🇸 Granada, Spain

Hopital Foch; 🇫🇷 Suresnes, France

John Hunter Hospital; 🇦🇺 New Lambton, New South Wales, Australia

Stadt Kliniken Koln; 🇩🇪 Koln, Germany

Chirurgische Universitätsklinik; 🇩🇪 Freiburg, Germany

Children's Memorial Health Institute; 🇵🇱 Warsaw, Poland

CHU Purpan; 🇫🇷 Toulouse, France

Royal Free Hospital; 🇬🇧 London, United Kingdom

Universitatsklinikum Heidelberg; 🇩🇪 Heidelberg, Germany

Hospital Virgen del Rocio; 🇪🇸 Sevilla, Spain

CHU Rangueil; 🇫🇷 Toulouse, France

CHU de Nancy-Brabois; 🇫🇷 Vandoeuvre-les-Nancy, France

University of Heidelberg; 🇩🇪 Heidelberg, Germany

Leids Universitair Medisch Centrum; 🇳🇱 Leiden, Netherlands

Erasmus Medical Center Rotterdam; 🇳🇱 Rotterdam, Netherlands

Institute of Transplantology, Medical University of Warsaw; 🇵🇱 Warsaw, Poland

Valle de Hebron; 🇪🇸 Barcelona, Spain

University Hospital Wurzburg; 🇩🇪 Wurzburg, Germany

Hospital Infanta Christa; 🇪🇸 Badajoz, Spain

Hospital Son Dureta; 🇪🇸 Palma De Mallorca, 07014, Spain

Hospital Reina Sofia; 🇪🇸 Cordoba, Spain

Complejo Hospitalario Univeritario de Santiago; 🇪🇸 Santiago De Compostela, Spain

Hospital Ramon Y Cajal; 🇪🇸 Madrid, Spain

Guys and St Thomas's Hospital; 🇬🇧 London, United Kingdom

University Hospital, Malmo; 🇸🇪 Malmo, Sweden

Karolinska University Hospital, Huddinge; 🇸🇪 Stockholm, Sweden

University Hospital A; 🇸🇪 Uppsala, Sweden

Fundacion Jimenez Diaz; 🇪🇸 Madrid, Spain

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

St George's Hospital; 🇬🇧 London, United Kingdom

Hospital Clinico San Carlos; 🇪🇸 Madrid, Spain

Hospital "Miguel Perez Carreno"; 🇻🇪 Caracas, Venezuela

Hospital Universitario de Caracas; 🇻🇪 Caracas, Venezuela

CHU Hotel Dieu; 🇫🇷 Nantes, France

Monash Medical Centre; 🇦🇺 Clayton, Victoria, Australia

Royal Melbourne Hospital; 🇦🇺 Parkville, Victoria, Australia

St Vincent's Hospital; 🇦🇺 Melbourne, Victoria, Australia

AKH Wien; 🇦🇹 Vienna, Austria

Med. Univ. Klinik; 🇦🇹 Graz, Austria

Hospital do Rim e Hipertensao; 🇧🇷 Sao Paulo, Brazil

Surgical Clinic Of Tartu University Clinics; 🇪🇪 Tartu, Estonia

West China Hospital of Sichuan University; 🇨🇳 Chengdu, Sichuan, China

Hopital Pellegrin, C.H.R.de Bordeaux; 🇫🇷 Bordeaux, France

Ruijin Hospital; 🇨🇳 Shanghai, Shanghai, China

Odense University Hospital; 🇩🇰 Odense, Denmark

Hospital du Bocage; 🇫🇷 Dijon, France

CHU de Grenoble; 🇫🇷 Grenoble, France

Hopital Jeanne de Flandres; 🇫🇷 Lille, France

Hopital Calmette; 🇫🇷 Lille, France

Centre Hospitalier Regional Universitaire; 🇫🇷 Limoges, France

Hopital Necker; 🇫🇷 Paris, France

Centre Hospitalier Lyon Sud; 🇫🇷 Pierre Benite, France

Hopital Tenon; 🇫🇷 Paris, France

Hospital Universitario de Maracaibo; 🇻🇪 Maracaibo, Venezuela

Princess Alexandra Hospital; 🇦🇺 Brisbane, Queensland, Australia

La Paz; 🇪🇸 Madrid, Spain

Hospital Sant Joan de Deu; 🇪🇸 Barcelona, Spain

Hospital Dr. Peset; 🇪🇸 Valencia, Spain