V. Medizinische Klinik, Universitätsklinikum Mannheim, University of Heidelberg, Mannheim, Germany.
Am J Transplant. 2010 Dec;10(12):2632-43. doi: 10.1111/j.1600-6143.2010.03256.x. Epub 2010 Sep 14.
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.
这项多中心、1:1 随机、平行分组、非劣效性研究比较了每日两次他克莫司（Tacrolimus BID；普乐可复）和每日一次他克莫司延长释放（Tacrolimus QD；Advagraf）与类固醇和小剂量吗替麦考酚酯联合应用，不进行抗体诱导，在 667 例新诊断的肾移植受者中进行。在 24 周时进行了双盲、双模拟 24 周的研究期，随后进行了长达 12 个月的开放性移植后扩展期。24 周时活检证实的急性排斥反应率（主要终点，按方案分析）为 Tacrolimus BID 组为 15.8%，Tacrolimus QD 组为 20.4%（p = 0.182；治疗差异为 4.5%，95%置信区间为-1.8%，10.9%，略超出预设的 10%非劣效性边界）。Kaplan-Meier 12 个月患者和移植物存活率分别为 Tacrolimus BID 组为 97.5%和 92.8%，QD 组为 96.9%和 91.5%。两组治疗均在 12 个月时保持良好的肾功能（平均肌酐清除率约为 67 mL/min），且不良反应谱相似。使用 Tacrolimus QD 或 BID（不进行抗体诱导）均可获得良好的总体结果，支持使用每日一次的制剂作为已确立的每日两次制剂的有效替代方案。
