Fixed Dose MMF vs Concentration Controlled MMF After Renal Transplantation

This study has been completed.
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by:
Erasmus Medical Center
ClinicalTrials.gov Identifier:
NCT00166244
First received: September 9, 2005
Last updated: February 11, 2009
Last verified: February 2009
  Purpose

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.


Condition Intervention Phase
De Novo Renal Transplant Recipient.
Drug: Mycophenolate Mofetil
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Erasmus Medical Center:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of patients treated for acute rejection during the first 3, 6, 12 months post-transplantation, [ Time Frame: 3, 6 and 12 Months ] [ Designated as safety issue: No ]
  • Time to first acute rejection, [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
  • Number of acute rejection episodes per patient in the first year post-transplantation, [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
  • Overall treatment outcome at 12 months post-transplantation which is composed of any one of the following: [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
  • Graft loss, [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
  • Death, [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
  • Discontinuation of MMF therapy, [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
  • Patient lost to follow-up. [ Time Frame: 12 Months ] [ Designated as safety issue: No ]

Enrollment: 901
Study Start Date: May 2003
Study Completion Date: April 2006
Primary Completion Date: March 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: 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.

Other Name: CellCept
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.
Drug: 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.

Other Name: CellCept

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.

  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00166244

  Show 67 Study Locations
Sponsors and Collaborators
Erasmus Medical Center
Hoffmann-La Roche
Investigators
Principal Investigator: Teun van Gelder, Dr Erasmus Medical Center
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr Teun van Gelder, Erasmus Medical Center
ClinicalTrials.gov Identifier: NCT00166244     History of Changes
Other Study ID Numbers: FDCC
Study First Received: September 9, 2005
Last Updated: February 11, 2009
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Erasmus Medical Center:
Mycophenolate mofetil
Therapeutic Drug Monitoring
Adult kidney transplantation
Paediatric kidney transplantation

Additional relevant MeSH terms:
Mycophenolate mofetil
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 21, 2014