Rivastigmine: a placebo controlled trial of twice daily and three times daily regimens in patients with Alzheimer's disease
Rivastigmine: a placebo controlled trial of twice daily and three times daily regimens in patients with Alzheimer's disease
复制标题
DOI：
10.1136/jnnp.2006.099424
复制
发表时间：
2007-10-01
影响因子：
11
通讯作者：
Lane, Roger
中科院分区：
文献类型：
--
作者：
Feldman, Howard H.;Lane, Roger
目的：评价快速滴定的利瓦斯明治疗轻中度阿尔茨海默病(AD)的疗效和安全性。方法：678例疑似AD患者接受安慰剂或利瓦斯明2~12 mg，每日2~12 mg，每日2次或3次。主要结果测量包括AD评估量表的认知子量表(ADAS-COG)和基于临床医生面谈的变化印象结合照顾者信息的分类分析(Cibic-Plus)。结果：26周时，TID组和BID组的平均剂量分别为9.6(2.76)mg/d和8.9(2.93)mg/d。与基线相比，TID组和BID组的平均ADAS-cog变化分别为20.2(SD 7.3)和1.2(SD 7.2)，而安慰剂组为2.8(SD 7.2)(p，0.05)。在Cibic-Plus分类应答分析中，利凡斯明TID和安慰剂之间的差异显著(31%比19%；p，0.05，意向治疗)。BID和安慰剂在这一结果指标上没有显著差异。不良反应主要发生在胃肠道，主要发生在剂量滴定过程中。因不良事件停药的患者占BID的17%，TID的11%，安慰剂的9%。结论：作为BID或TID方案的利瓦斯明可显著改善AD患者的认知、功能和整体表现。TID方案显示出更好的耐受性，并允许滴定到更高的剂量，这一结果意义重大，因为利瓦斯明的疗效与剂量有关。
Objective: To evaluate the efficacy and safety of rapidly titrated rivastigmine administered twice ( BID) or three times ( TID) daily in patients with mild to moderate Alzheimer's disease ( AD).Methods: This was a 26 week international, randomised, double blind, placebo controlled study in which 678 patients with probable AD received placebo or rivastigmine 2 - 12 mg/ day BID or TID. Primary outcome measures included the cognitive subscale of the AD Assessment Scale ( ADAS- cog) and categorical analysis of the Clinician Interview Based Impression of Change incorporating caregiver information ( CIBIC- Plus). Secondary outcomes were the CIBIC- Plus change from baseline, Progressive Deterioration Scale, ADAS-cogA, Mini- Mental State Examination and Global Deterioration Scale.Results: At week 26, mean rivastigmine dose was 9.6 ( 2.76) mg/ day in the TID group and 8.9 ( 2.93) mg/ day in the BID group. Mean ADAS- cog changes from baseline in the TID and BID rivastigmine treated groups were 20.2 ( SD 7.3) and 1.2 ( SD 7.2) versus 2.8 ( SD 7.2) for the placebo group ( p, 0.05). Differences between rivastigmine TID and placebo on the CIBIC- Plus categorical responder analysis were significant ( 31% vs 19%; p, 0.05, intention to treat). No significant differences were seen between BID and placebo for this outcome measure. Adverse events were predominantly gastrointestinal, occurring mainly during dose titration. Withdrawal because of adverse events accounted for 17% of BID, 11% of TID and 9% of placebo patients.Conclusions: Rivastigmine administered as a BID or TID regimen significantly benefited cognitive, function and global performances in AD patients. The TID regimen showed a tendency for superior tolerability and permitted titration to higher doses, an outcome that is significant as the efficacy of rivastigmine is dose related.