20 / 10 / 16
关于“verubecestat治疗前驱期阿尔茨海默病的随机试验”一文医学翻译摘要学习情况，记录于此。
Randomized Trial of Verubecestat for Prodromal Alzheimer’s Disease
背景
BACKGROUND
对于在痴呆出现之前改变脑内淀粉样蛋白沉积的药物，前驱期阿尔茨海默病为其提供了药效检验机会。
Prodromal Alzheimer’s disease offers an opportunity to test the effect of drugs that modify the deposition of amyloid in the brain before the onset of dementia.
笔记：
verubecestat是一种口服的淀粉样前体蛋白β位点裂解酶-1（BACE-1）抑制剂，能够阻断淀粉样蛋白β（Aβ）的产生。
Verubecestat is an orally administered β-site amyloid precursor protein–cleaving enzyme 1 (BACE-1) inhibitor that blocks production of amyloid-beta (Aβ).
笔记：
在对阿尔茨海默病所致轻至中度痴呆患者开展的一项试验中，本药未能阻止疾病的临床进展。
The drug did not prevent clinical progression in a trial involving patients with mild-to-moderate dementia due to Alzheimer’s disease.
笔记：
方法
METHODS
我们开展了一项为期104周的随机、双盲、安慰剂对照试验，在有记忆障碍和脑内淀粉样蛋白水平升高，但病情不符合痴呆定义的患者中比较了每日12 mg和40 mg剂量的verubecestat与安慰剂。
We conducted a randomized, double-blind, placebo-controlled, 104-week trial to evaluate verubecestat at doses of 12 mg and 40 mg per day, as compared with placebo, in patients who had memory impairment and elevated brain amyloid levels but whose condition did not meet the case definition of dementia.
笔记：
主要结局是临床痴呆评定量表-总分（Clinical Dementia Rating Scale - Sum of Boxes [CDR-SB]；评分范围为0～18分，较高的评分表示较差的认知和日常功能）从基线至第104周的变化。
The primary outcome was the change from baseline to week 104 in the score on the Clinical Dementia Rating Scale–Sum of Boxes (CDR-SB; scores range from 0 to 18, with higher scores indicating worse cognition and daily function).
笔记：
主要结局 primary outcome
临床痴呆评定量表 Clinical Dementia Rating Scale}
次要结局包括对认知和日常功能的其他评估。
Secondary outcomes included other assessments of cognition and daily function.
结果
RESULTS
纳入1,454例患者后，本试验因无效（futility）而终止；485例患者被分配接受12 mg/d剂量的verubecestat治疗（12 mg组），484例接受40 mg/d剂量的verubecestat治疗（40 mg组），485例接受安慰剂治疗。
The trial was terminated for futility after 1454 patients had been enrolled; 485 had been assigned to receive verubecestat at a dose of 12 mg per day (the 12-mg group), 484 to receive verubecestat at a dose of 40 mg per day (the 40-mg group), and 485 to receive placebo..
笔记：
各组分别共有234例患者、231例患者和239例患者完成了104周的试验治疗方案。
A total of 234 patients, 231 patients, and 239 patients per group, respectively, completed 104 weeks of the trial regimen.
在12 mg组、40 mg组和安慰剂组中，CDR-SB评分从基线至第104周的估计平均变化分别为1.65、2.02和1.58（12 mg组和安慰剂组之间的比较，P=0.67；40 mg组和安慰剂组之间的比较，P=0.01），这些结果提示，较大剂量组的结局比安慰剂组差。
The estimated mean change from baseline to week 104 in the CDR-SB score was 1.65 in the 12-mg group, 2.02 in the 40-mg group, and 1.58 in the placebo group (P=0.67 for the comparison between the 12-mg group and the placebo group and P=0.01 for the comparison between the 40-mg group and the placebo group), suggesting a worse outcome in the higher-dose group than in the placebo group.
笔记：
在12 mg组、40 mg组和安慰剂组中，进展至阿尔茨海默病所致痴呆的发生率分别为24.5起事件/100患者-年、25.5起事件/100患者-年和19.3起事件/100患者-年（40 mg *vs.*安慰剂的风险比，1.38；97.51%置信区间，1.07～1.79，未进行多重比较校正），安慰剂的结果较好。
The estimated rate of progression to dementia due to Alzheimer’s disease was 24.5, 25.5, and 19.3 events per 100 patient-years in the 12-mg group, the 40-mg group, and the placebo group, respectively (hazard ratio for 40 mg vs. placebo, 1.38; 97.51% confidence interval, 1.07 to 1.79, not adjusted for multiple comparisons), favoring placebo.
verubecestat组的不良事件发生率高于安慰剂组。
Adverse events were more common in the verubecestat groups than in the placebo group.
笔记：
结论
CONCLUSIONS
在前驱期阿尔茨海默病患者中，verubecestat未改善痴呆的临床评分，并且一些指标提示，verubecestat组患者的认知和日常功能比安慰剂组患者差（由默沙东公司资助；在ClinicalTrials.gov注册号为NCT01953601）。
Verubecestat did not improve clinical ratings of dementia among patients with prodromal Alzheimer’s disease, and some measures suggested that cognition and daily function were worse among patients who received verubecestat than among those who received placebo. (Funded by Merck Sharp & Dohme; ClinicalTrials.gov number, NCT01953601 .)
笔记：