摘要
目的评价美金刚对阿尔茨海默病(Alzheimer disease,AD)患者的疗效与安全性。方法多中心、随机、双盲、安慰剂对照研究。共纳入 AD 患者258例(MMSE 检查5～18分),随机分入安慰剂组(PBO,n=130)或美金刚组(MEM,n=128),分别仅给予安慰剂或安慰剂及美金刚(10～20mg/d)治疗,共16周。主要疗效评估以坚持服用研究药物并在第16周接受严重障碍量表(SIB)评估的患者(完成16周研究集,CS16集)为对象,以 SIB 评分相对于基线的变化为指标;次要疗效评估分别以 CS16集和全分析集(FAS)为对象,以 MMSE、神经精神科问卷(NPI)和 AD 合作研究-日常生活能力量表(ADCS-ADL_(19))为指标。安全性评估包括体格检查、实验室检查、心电图和不良事件。结果共236例患者(MEM 117例;PBO 119例)进入疗效分析,尽管两组的 SIB 评分均较基线时有所提高,两组的主要和次要疗效分析差异均无统计学意义(均 P>0.05)。Post-hoc 数据评估发现有两个因素造成疗效分析结果的偏倚,舍弃受这些因素影响的患者数据后再次进行分析:美金刚组(n=94)的16周末 SIB(MEM:PBO=2.2:0.3,P=0.04)、MMSE(MEM:PBO=1.0:0.1,P=0.03)和 ADL 评分变化(MEM:PBO=0.1:-1.6,P=0.02)与安慰剂组(n=95)差异均有统计学意义,提示美金刚的疗效优于安慰剂,显著改善 AD 患者的认知功能,并使日常生活能力维持稳定。美金刚的耐受性良好,其不良事件特征与安慰剂相似。结论本研究为已有资料提供了更多支持,表明美金刚对中重度 AD患者有效、安全且耐受性良好。
Objective To evaluate the efficacy and safety of memantine in the treatment of patients with Alzheimer＇s disease （AD）. Methods This was a 16-week, multi-center, randomized, double blind, placebo-controlled clinical trial （Study 10116 ）. A total of 258 AD patients （MMSE score 5-18 ） were randomized in a 1：1 ratio into either memantine 10-20 mg/day （MEM, n = 128 ） or placebo （PBO, n = 130） group for 16 weeks. Efficacy was primarily assessed in terms of changes of severe impairment battery （SIB） score in patients from baseline up to SIB assessment in the 16th week （16-week completers set, CS16）. While changes of MMSE, ADCS-ADLI9, and NPI （ neuropsychiatric inventory） were evaluated as secondary efficacy parameters on both CS16 and full-analysis set （FAS）. Safety was assessed by physical examination, lab assays, ECG, and adverse events. Results 236 subjects （CS16： MEM n = 117, PBO n= 119） were eligible for the efficacy assessment. No statistically significant difference between the treatments was observed on the primary and secondary efficacy analysis, although both treatment groups had a slight increase from baseline in SIB total score. Post hoc evaluation of the data identified two bias factors that had a significant impact on the results of the pre-protocol specified primary and secondary analyses. In a re-analysis of the data （ CS16modified, MEM n = 94, PBO n = 95 ） excluding patient data affected by these factors, memantine-treated patients showed a statistically significant improvement related to placebo in the 16th week on the SIB （ MEM 2. 2 vs PBO 0. 3, P = 0. 04）, MMSE （ MEM 1.0 vs PBO 0. 1, P = 0. 03 ）, and ADL （ MEM 0. 1 vs PBO - 1.6, P = 0.02） scales, indicating that memantine improved the cognitive function of AD patients and stabilized the activity of daily life. Memantine was well tolerated with an adverse event profile similar to that of placebo. Conclusion This study provides further support for pre-existing data, showing that memantine is efficacious, safe, and well-tolerated in patients with moderate to severe AD.
出处
《中华神经科杂志》
CAS
CSCD
北大核心
2007年第6期364-368,共5页
Chinese Journal of Neurology
