他克莫司缓释胶囊与他克莫司胶囊的临床对照试验

目的 比较和评价首次肾移植受者使用他克莫司缓释胶囊和他克莫司胶囊治疗的安全性和有效性.方法 11家中心的241例肾移植受者随机分配为试验组(应用他克莫司缓释胶囊+吗替麦考酚酯+皮质激素)和对照组(应用他克莫司胶囊+吗替麦考酚酯+皮质激素),观察时间从移植当天至术后12周.试验组受试者每天上午一次性服用他克莫司缓释胶囊,对照组受试者每天早晚分2次服用他克莫司胶囊.两组试验药物的起始剂量均为0.1～0.15 mg·kg-1·d-1.分别在治疗前和治疗后第1、3、7、14、28、56和84 d各随访1次.对两组受者用药的有效性、安全性、依从性以及不良反应进行对比分析.结果 进入符合方案分析集者共223例,其中试验组111例,对照组112例.两组受者的平均年龄、性别、原发病的差异均无统计学意义,各有12例发生急性排斥反应.对照组和试验组分别有36例(32.1%)和37例(33.3%)发生与试验药物相关的不良反应.无受者连续3 d未按照方案服用药物.两组治疗后期较治疗前期的服药量均减少,且组内差异有统计学意义(P<0.05).治疗早期两组血他克莫司浓度较接近,从28 d开始,试验组血药浓度低于对照组,但差异无统计学意义.结论 从药物安全性、药物治疗的有效性、相关不良反应以及受者依从性各方面分析显示,每天1次的他可莫司缓释胶囊均非劣效于每天2次的他克莫司胶囊,在临床应用中,用他克莫司缓释胶囊代替他克莫司胶囊是切实可行的.

Abstract：

Objective To compare the efficacy and safety of twice-daily tacrolimus (Tacrolimus BID; Prograf) vs once-daily prolonged release tacrolimus (Tacrolimus QD; Advagraf), combined with steroids and mycophenolate mofetil in preventing acute rejection in De Novo renal transplantation patients. Methods 241 patients from 11 centers were randomized into two groups with 3 months observation period post-transplantation. Advagraf was administered as a single oral dose in the morning (initially 0. 1-0. 15 mg/kg every day) and Prograf was administered in two equal oral doses 12h apart (initially 0. 1-0. 15 mg/kg). Study visits were scheduled for days 1, 3, 7, 14, 28, 56, 84post-transplantion. The efficacy, safety, compliance and adverse effects were compared between two groups. Results Totally 223 patients completed the study. The two groups were comparable in age,gender and primary disease. There were 12 episodes of acute rejection in each group. There was no graft loss or patient death in both groups. The incidence of drug related adverse events was 32. 1 %and 33. 3% respectively in the control and experimental groups. Dosage was decreased in both groups and there was significant difference in each group. The trough level was similar at the initiate period.Twenty-eight days post-transplantation the trough level in the Advagraf group was lower than in the Prograf group. Conclusion Advagraf has the same efficacy, safety and drug related adverse effects as Prograf. It is practical and feasible for Advagraf substitute for Prograf in clinical practice.