Conversion from twice-daily tacrolimus to once-daily extended release tacrolimus (LCPT): The phase III randomized MELT trial.
Bunnapradist S, Ciechanowski K, et al.American Journal of Transplantation. 2013; 13(3):760-769
Aims
To compare the efficacy and safety of once daily extended release tacrolimus (LCPT) tablets with the twice daily tacrolimus capsules in adult renal transplant patients.
Interventions
Conversion of tacrolimus twice daily to LCPT or the continuation of tacrolimus twice daily with maintenance therapy.
Participants
326 adult renal transplant recipients on a stable tacrolimus dose.
Outcomes
The primary efficacy outcome included the proportion of patients with efficacy failures (deaths, graft failure, locally read BPAR) or lost to follow up. The secondary outcomes assessed after 6 months included: the efficacy failure in the per protocol population, incidence of individual components of the composite efficacy endpoint; incidence of steroid resistant acute rejection and clinically suspected and treated rejection episodes, severity grades of the first episode of BPAR and incidence of premature discontinuation of the randomly assigned drug.
Follow-up
12 months.
CET Conclusions
Patients were converted from twice daily Tacrolimus to LCPT between 3 months and 5 years post-transplant. The design was a non-inferiority trial with a composite endpoint, namely death, graft failure, rejection, loss to follow up and was 2.5% in both groups with a 95%CI of -4.2% to 4.2%. Serum Tacrolimus levels were the same between groups with lower dosing in the LCPT group. Adverse events were similar between the groups, but, premature discontinuation of LCPT was significantly higher than twice daily Tacrolimus (20 versus 8 patients, p=0.03). This may represent the difficulty of conversion trials for patients stable on a particular drug. However an important argument for the use of once daily preparations is improved compliance, which was not demonstrated in this study.
Data analysis
Modified intention-to-treat analysis
Trial registration
ClinicalTrials.gov - NCT00817206