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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/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/ct2/show/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.
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/ct2/show/NCT00166244