A randomized, open-label study of sirolimus versus cyclosporine in primary de novo renal allograft recipients.
Flechner SM, Gurkan A, et al.Transplantation 2013; 95(10): 1233-1241.
Aims
To investigate whether a calcineurin inhibitor free regimen including sirolimus, mycophenolate mofetil (MMF), corticosteroids (CS) and an anti-interleukin-2 receptor antibody improves long term renal function in de novo allograft recipients.
Interventions
Patients received either sirolimus or cyclosporine A in combination with basiliximab, MMF and CS.
Participants
475 patients with end stage renal disease who had received a primary renal allograft.
Outcomes
The outcomes included renal function, graft and patient survival, delayed graft function, biopsy confirmed acute rejection and adverse events.
Follow-up
104 weeks however the study was terminated early.
CET Conclusions
This paper reports an open-label RCT comparing the use of sirolimus and cyclosporine A in de-novo renal transplant recipients receiving IL2-antibody induction, MMF and corticosteroids. The trial was terminated early after interim analysis identified an excess of acute rejection in the sirolimus group (21.4% versus 6.1%) and excess adverse events (17.4% versus 6.8%). These results are interesting, and in contrast to those from a Cochrane review of the topic in 2009 (Webster et al.). Coupled with the increased risk of early wound complications and lymphoceles, this casts further doubt on the use of mTOR inhibitors in primary immunosuppressive strategies. It is, however, worth noting that the acute rejection rate of 6.8% in the control group is particularly low, possibly due to the recruitment of low-risk patients to the trial.
Data analysis
Modified intention-to-treat analysis
Trial registration
ClinicalTrials.gov – NCT00137345