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.

Abstract

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.