An Open, Prospective, Randomised, Controlled, Multi-Center Study Comparing Fixed Dose vs Concentration Controlled Mycophenolate Mofetil Regimens for de Novo Patients Following Transplantation
Overview
- Phase
- Phase 4
- Intervention
- Mycophenolate Mofetil
- Conditions
- De Novo Renal Transplant Recipient.
- Sponsor
- Erasmus Medical Center
- Enrollment
- 901
- Locations
- 67
- Primary Endpoint
- 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.
- Status
- Completed
- Last Updated
- 17 years ago
Overview
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.
Investigators
Eligibility 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,
Arms & Interventions
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.
Intervention: Mycophenolate Mofetil
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.
Intervention: Mycophenolate Mofetil
Outcomes
Primary Outcomes
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
Secondary Outcomes
- 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)