Fixed Dose MMF vs Concentration Controlled MMF After Renal Transplantation

Erasmus University

Status and phase: Completed; Phase 4

Conditions: De Novo Renal Transplant Recipient.

Treatments: Drug: Mycophenolate Mofetil

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00166244

FDCC

Details and patient eligibility

About

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.

Full 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.

Enrollment: 901 patients

Sex: All

Ages: 2+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

901 participants in 2 patient groups

Fixed Dose

Active Comparator group

Description:

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.

Treatment:

Drug: Mycophenolate Mofetil

Concentration Controlled

Active Comparator group

Description:

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:

Drug: Mycophenolate Mofetil