A phase III prospective, randomized study to evaluate concentration-controlled sirolimus (rapamune) with cyclosporine dose minimization or elimination at six months in de novo renal allograft recipients

Background This study evaluated the safety and efficacy of sirolimus plus steroids as a maintenance regimen with or without small-dose cyclosporine (CsA) adjunctive therapy in renal transplant recipients. Methods. A total of 133 recipients of kidney allograft transplantations recruited in the United Kingdom and Ireland were enrolled into the study and are presented in this interim analysis. In the first 3 months, all patients received CsA plus sirolimus and small-dose steroids after transplantation. At 3 months, patients were randomized 1:1 to CsA elimination (e)CsA or CsA dose minimization (m)CsA. Dosing of agents was concentration-controlled and open label. Results. Patient and graft survival were 97.7% and 95.5%, respectively (n=133), whereas the biopsy-proven acute rejection rate in the first 6 months was 19.5% (26 episodes in 133 patients); incidents of acute rejection rates comprised 22 episodes (16.5%) during the first 3 months of the study and four episodes (3%) after randomization. Eighty-seven patients were randomized to receive eCsA or mCsA. At 6 months, creatinine clearance was significantly higher in the eCsA group versus mCsA group, respectively (65 mL/min vs. 57 mL/min; P=0.027). There was no significant difference in serum cholesterol, triglycerides, low-density lipoprotein, or high-density lipoprotein levels between the groups. Conclusion. These data demonstrate that withdrawal of CsA from a small-dose sirolimus maintenance regimen is safe and is associated with an improvement in renal function. The study also suggests that the addition of small-dose CsA to a sirolimus maintenance regimen does not increase immunosuppressive efficacy.