ADHERE: Randomized controlled trial comparing renal function in de novo kidney transplant recipients receiving prolonged-release tacrolimus plus MMF or sirolimus.
Rummo OO, Carmellini M, et al.Transplant International 2016 [record in progress].
Aims
To compare renal function post-kidney transplant in patients who received prolonged release tacrolimus-based immunosuppressive regimens.
Interventions
Participants were randomized on Day 28 following transplantation to receive either prolonged-release tacrolimus plus mycophenolate mofetil (Arm 1) or prolonged-release tacrolimus (≥25% dose reduction on Day 42) plus sirolimus (Arm 2).
Participants
569 patients aged ≥18 years old with end-stage kidney disease, suitable for primary renal transplantation or re-transplantation and receiving a kidney transplant from a deceased or living (nonhuman leukocyte antigen identical) donor with compatible ABO blood type.
Outcomes
The primary outcome measured was glomerular filtration rate by iohexol clearance at week 52. Secondary measured outcomes included renal function, estimated glomerular filtration rate, creatinine clearance, efficacy failure (patient withdrawal or graft loss), clinical acute rejection, biopsy confirmed acute rejection, patient and graft survival and delayed graft function.
Follow-up
1 year
CET Conclusions
This large, industry-funded multicentre study randomised 730 renal transplant recipients to either MMF or sirolimus, in conjunction with modified-release tacrolimus, from day 28 post-transplant. In the sirolimus arm, tacrolimus dose was reduced by at least 25% to aim for a trough level of 4-5 ng/ml. At 52 weeks, there was no difference in measured GFR. Composite efficacy failure was higher in the sirolimus arm due to a greater number of withdrawals for adverse events. The size of the study is impressive and appears to demonstrate no advantage to the sirolimus regimen. There are, however, a few points of note. The target trough tacrolimus levels in the sirolimus arm were not reached, which may have been detrimental to renal function. Follow-up is short, meaning that any benefit in terms of reduced tacrolimus exposure may not yet be apparent. As the study is unblinded, and the decision to withdraw sirolimus is at the discretion of the treating physician, there is a risk of bias in the composite endpoint used. Of the 730 randomised patients, only 77.9% underwent primary endpoint assessment, demonstrating the difficulty in using a measured GFR endpoint in clinical trials.
Data analysis
Modified intention-to-treat analysis
Trial registration
ClinicalTrials.gov - NCT01363752