De novo low-dose sirolimus versus mycophenolate mofetil in combination with extended-release tacrolimus in kidney transplant recipients: a multicentre, open-label, randomized, controlled, non-inferiority trial.
Huh KH, Lee JG, et al.Nephrology Dialysis Transplantation 2017; 32(8): 1415-1424.
Aims
To compare the efficacy and safety of low-dose sirolimus (SRL) versus mycophenolate mofetil (MMF) in combination with a reduced dose of extended-release tacrolimus (ER-TAC) in kidney transplant recipients.
Interventions
Participants were randomly assigned to receive ER-TAC with either SRL (investigational group) or MMF (control group).
Participants
159 patients aged ≥ 20 years, scheduled to receive a single-organ kidney transplant from either a living donor or deceased donor.
Outcomes
The primary outcome measured was the efficacy failure rate at 12 months post transplantation, a composite of biopsy-proven acute rejection (BPAR), graft loss, patient death and patient loss to follow-up. Secondary outcomes included estimated glomerular filtration rate by modification of diet in renal disease, incidence of BPAR, overall survival and allograft survival.
Follow-up
12 months
CET Conclusions
This paper reports a non-inferiority randomised controlled trial of low-dose sirolimus and ER-tacrolimus versus MMF and ER-tacrolimus. All patients received basiliximab induction and corticosteroids (the dose of which is not reported). Primary endpoint is a composite of BPAR, graft loss, death or loss to follow-up during the first 12 months post-transplant. The authors conclude that the low-dose sirolimus arm (achieving trough levels of around 5 ng/ml) is non-inferior to MMF, with similar renal function at 12 months. In fact, the MMF arm appears numerically worse than sirolimus, with a rejection rate of 13.3% vs. 5.3%, although this does not reach statistical significance. This may well reflect the imbalance between study arms, with more retransplants and higher levels of HLA-B and HLA-DR mismatches in the MMF arm. Despite this, the rejection rate of 5.3% in the sirolimus arm, with monoclonal antibody induction, is impressive and certainly worth of further investigation. Usual mTORi caveats apply, with numerically higher wound complication and withdrawal rates in the sirolimus arm. Generalisability may be limited – the study population is mainly Asian, with no DCD kidneys or polyclonal antibody induction included.
Data analysis
Modified intention-to-treat analysis
Trial registration
ClinicalTrials.gov - NCT01680952