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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00166244




Registration number
NCT00166244
Ethics application status
Date submitted
9/09/2005
Date registered
14/09/2005
Date last updated
12/02/2009

Titles & IDs
Public title
Fixed Dose MMF vs Concentration Controlled MMF After Renal Transplantation
Scientific title
An Open, Prospective, Randomised, Controlled, Multi-Center Study Comparing Fixed Dose vs Concentration Controlled Mycophenolate Mofetil Regimens for de Novo Patients Following Transplantation
Secondary ID [1] 0 0
FDCC
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
De Novo Renal Transplant Recipient. 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Mycophenolate Mofetil

Active comparator: Fixed Dose - 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.

Active comparator: Concentration Controlled - 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.


Treatment: Drugs: Mycophenolate Mofetil
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
12 Months
Secondary outcome [1] 0 0
Proportion of patients treated for acute rejection during the first 3, 6, 12 months post-transplantation,
Timepoint [1] 0 0
3, 6 and 12 Months
Secondary outcome [2] 0 0
Time to first acute rejection,
Timepoint [2] 0 0
12 Months
Secondary outcome [3] 0 0
Number of acute rejection episodes per patient in the first year post-transplantation,
Timepoint [3] 0 0
12 Months
Secondary outcome [4] 0 0
Overall treatment outcome at 12 months post-transplantation which is composed of any one of the following:
Timepoint [4] 0 0
12 Months
Secondary outcome [5] 0 0
Graft loss,
Timepoint [5] 0 0
12 Months
Secondary outcome [6] 0 0
Death,
Timepoint [6] 0 0
12 Months
Secondary outcome [7] 0 0
Discontinuation of MMF therapy,
Timepoint [7] 0 0
12 Months
Secondary outcome [8] 0 0
Patient lost to follow-up.
Timepoint [8] 0 0
12 Months

Eligibility
Key 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.
Minimum age
2 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/05/2003
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/04/2006
Sample size
Target
Accrual to date
Final
901
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
John Hunter Hospital - New Lambton
Recruitment hospital [2] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [3] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [4] 0 0
St Vincent's Hospital - Melbourne
Recruitment hospital [5] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [6] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [7] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2305 - New Lambton
Recruitment postcode(s) [2] 0 0
4102 - Brisbane
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3065 - Melbourne
Recruitment postcode(s) [5] 0 0
3052 - Parkville
Recruitment postcode(s) [6] 0 0
6009 - Nedlands
Recruitment postcode(s) [7] 0 0
6847 - Perth
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Graz
Country [2] 0 0
Austria
State/province [2] 0 0
Vienna
Country [3] 0 0
Belgium
State/province [3] 0 0
Leuven
Country [4] 0 0
Brazil
State/province [4] 0 0
Sao Paulo
Country [5] 0 0
Canada
State/province [5] 0 0
British Columbia
Country [6] 0 0
China
State/province [6] 0 0
Shanghai
Country [7] 0 0
China
State/province [7] 0 0
Sichuan
Country [8] 0 0
Denmark
State/province [8] 0 0
Odense
Country [9] 0 0
Estonia
State/province [9] 0 0
Tartu
Country [10] 0 0
France
State/province [10] 0 0
Bordeaux
Country [11] 0 0
France
State/province [11] 0 0
Dijon
Country [12] 0 0
France
State/province [12] 0 0
Grenoble
Country [13] 0 0
France
State/province [13] 0 0
Kremlin Bicêtre
Country [14] 0 0
France
State/province [14] 0 0
Lille
Country [15] 0 0
France
State/province [15] 0 0
Limoges
Country [16] 0 0
France
State/province [16] 0 0
Nantes
Country [17] 0 0
France
State/province [17] 0 0
Paris
Country [18] 0 0
France
State/province [18] 0 0
Pierre Benite
Country [19] 0 0
France
State/province [19] 0 0
Suresnes
Country [20] 0 0
France
State/province [20] 0 0
Toulouse
Country [21] 0 0
France
State/province [21] 0 0
Vandoeuvre-les-Nancy
Country [22] 0 0
Germany
State/province [22] 0 0
Berlin
Country [23] 0 0
Germany
State/province [23] 0 0
Freiburg
Country [24] 0 0
Germany
State/province [24] 0 0
Heidelberg
Country [25] 0 0
Germany
State/province [25] 0 0
Koln
Country [26] 0 0
Germany
State/province [26] 0 0
Wurzburg
Country [27] 0 0
Lithuania
State/province [27] 0 0
Vilnius
Country [28] 0 0
Netherlands
State/province [28] 0 0
Leiden
Country [29] 0 0
Netherlands
State/province [29] 0 0
Rotterdam
Country [30] 0 0
Norway
State/province [30] 0 0
Oslo
Country [31] 0 0
Poland
State/province [31] 0 0
Warsaw
Country [32] 0 0
Spain
State/province [32] 0 0
07014
Country [33] 0 0
Spain
State/province [33] 0 0
Badajoz
Country [34] 0 0
Spain
State/province [34] 0 0
Barcelona
Country [35] 0 0
Spain
State/province [35] 0 0
Cordoba
Country [36] 0 0
Spain
State/province [36] 0 0
Granada
Country [37] 0 0
Spain
State/province [37] 0 0
Madrid
Country [38] 0 0
Spain
State/province [38] 0 0
Santiago De Compostela
Country [39] 0 0
Spain
State/province [39] 0 0
Sevilla
Country [40] 0 0
Spain
State/province [40] 0 0
Valencia
Country [41] 0 0
Sweden
State/province [41] 0 0
Malmo
Country [42] 0 0
Sweden
State/province [42] 0 0
Stockholm
Country [43] 0 0
Sweden
State/province [43] 0 0
Uppsala
Country [44] 0 0
Taiwan
State/province [44] 0 0
Taipei
Country [45] 0 0
United Kingdom
State/province [45] 0 0
London
Country [46] 0 0
Venezuela
State/province [46] 0 0
Caracas
Country [47] 0 0
Venezuela
State/province [47] 0 0
Maracaibo

Funding & Sponsors
Primary sponsor type
Other
Name
Erasmus Medical Center
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Hoffmann-La Roche
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00166244
Trial related presentations / 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.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Teun van Gelder, Dr
Address 0 0
Erasmus Medical Center
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00166244