Black S E, Doody R, Li H, McRae T, Jambor K M, Xu Y, Sun Y, Perdomo C A, Richardson S
Division of Neurology, Department of Medicine and Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Ontario, Canada.
Neurology. 2007 Jul 31;69(5):459-69. doi: 10.1212/01.wnl.0000266627.96040.5a.
To evaluate the efficacy and safety of donepezil for severe Alzheimer disease (AD).
Patients with severe AD (Mini-Mental State Examination [MMSE] scores 1 to 12 and Functional Assessment Staging [FAST] scores > or =6) were enrolled in this multinational, double-blind, placebo-controlled trial at 98 sites. Patients were randomized to donepezil 10 mg daily or placebo for 24 weeks. Primary endpoints were the Severe Impairment Battery (SIB) and Clinician's Interview-Based Impression of Change-Plus caregiver input (CIBIC-Plus). Secondary endpoints included the MMSE, the Alzheimer Disease Cooperative Study-Activities of Daily Living-severe version (ADCS-ADL-sev), the Neuropsychiatric Inventory (NPI), the Caregiver Burden Questionnaire (CBQ), and the Resource Utilization for Severe Alzheimer Disease Patients (RUSP). Efficacy analyses were performed in the intent-to-treat (ITT) population using last post-baseline observation carried forward (LOCF). Safety assessments were performed for patients receiving > or =1 dose of donepezil or placebo.
Patients were randomized to donepezil (n = 176) or placebo (n = 167). Donepezil was superior to placebo on SIB score change from baseline to endpoint (least squares mean difference 5.32; p = 0.0001). CIBIC-Plus and MMSE scores favored donepezil at endpoint (p = 0.0473 and p = 0.0267). Donepezil was not significantly different from placebo on the ADCS-ADL-sev, NPI, CBQ, or RUSP. Adverse events reported were consistent with the known cholinergic effects of donepezil and with the safety profile in patients with mild to moderate AD.
Patients with severe AD demonstrated greater efficacy compared to placebo on measures of cognition and global function.
评估多奈哌齐治疗重度阿尔茨海默病（AD）的疗效和安全性。
重度AD患者（简易精神状态检查表[MMSE]评分1至12分且功能评估分期[FAST]评分≥6分）被纳入这项在98个地点开展的多国、双盲、安慰剂对照试验。患者被随机分为每日服用10 mg多奈哌齐组或安慰剂组，为期24周。主要终点为严重损害量表（SIB）和基于临床医生访谈的变化印象加照顾者意见（CIBIC-Plus）。次要终点包括MMSE、阿尔茨海默病协作研究日常生活活动严重版（ADCS-ADL-sev）、神经精神科问卷（NPI）、照顾者负担问卷（CBQ）以及重度阿尔茨海默病患者资源利用情况（RUSP）。在意向性治疗（ITT）人群中采用末次观察值结转（LOCF）进行疗效分析。对接受≥1剂多奈哌齐或安慰剂的患者进行安全性评估。
患者被随机分为多奈哌齐组（n = 176）和安慰剂组（n = 167）。从基线到终点，多奈哌齐组的SIB评分变化优于安慰剂组（最小二乘均值差异为5.32；p = 0.0001）。终点时，CIBIC-Plus和MMSE评分有利于多奈哌齐组（p = 0.0473和p = 0.0267）。在ADCS-ADL-sev、NPI、CBQ或RUSP方面，多奈哌齐组与安慰剂组无显著差异。报告的不良事件与多奈哌齐已知的胆碱能效应以及轻至中度AD患者的安全性特征一致。
与安慰剂相比，重度AD患者在认知和整体功能测量指标上显示出更大疗效。
