Tacrolimus Once Daily (ADVAGRAF) Versus Twice Daily (PROGRAF) in de Novo Renal Transplantation: A Randomized Phase III Study

• Autor(a) principal: Kraemer, B. K.
• Data de Publicação: 2010
• Outros Autores: Charpentier, B., Backman, L., Silva, H. Tedesco [UNIFESP], Mondragon-Ramirez, G., Cassuto-Viguier, E., Mourad, G., Sola, R., Rigotti, P., Ortuno Mirete, J., Tacrolimus Prolonged Release Rena
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: http://dx.doi.org/10.1111/j.1600-6143.2010.03256.x; http://repositorio.unifesp.br/handle/11600/33093
• topic: Biopsy-proven acute rejection; immunosuppression; kidney transplantation; noninferiority study; prolonged-release tacrolimus; tacrolimus

This multicenter, 1:1-randomized, parallel-group, noninferiority study compared the efficacy and safety of twice-daily tacrolimus (Tacrolimus BID; Prograf) and once-daily tacrolimus prolonged release (Tacrolimus QD; Advagraf), combined with steroids and low-dose mycophenolate mofetil without antibody induction, in 667 de novo kidney transplant recipients. A double-blind, double-dummy 24-week period was followed by an open extension of up to 12 months posttransplant. Biopsy-proven acute rejection rate at 24 weeks (primary endpoint, per-protocol analysis) was 15.8% for Tacrolimus BID versus 20.4% for Tacrolimus QD (p = 0.182; treatment difference 4.5%, 95% confidence interval-1.8%, 10.9%, just outside the prespecified 10% noninferiority margin). Kaplan-Meier 12-month patient and graft survival rates were 97.5% and 92.8% for Tacrolimus BID and 96.9% and 91.5% for QD. Both treatment groups showed equally well-maintained renal function at 12 months (mean creatinine clearance approximately 67 mL/min) and similar adverse event profiles. Overall results obtained with either Tacrolimus QD or BID, without antibody induction, were good, supporting use of the once-daily formulation as an effective alternative to the established twice-daily formulation.