A Double-Blind, Delayed-Start Trial of Rasagiline in Parkinson's Disease
A Double-Blind, Delayed-Start Trial of Rasagiline in Parkinson's Disease
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DOI：
10.1056/nejmoa0809335
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发表时间：
2009-09-24
影响因子：
158.5
通讯作者：
Tolosa, Eduardo
中科院分区：
文献类型：
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作者：
Olanow, C. Warren;Rascol, Olivier;Tolosa, Eduardo
背景减缓疾病进展的疗法是帕金森病的主要未满足需求。方法在这项双盲试验中，我们检查了雷沙吉兰对帕金森病具有疾病缓解作用的可能性。共有 1176 名未经治疗的帕金森病受试者被随机分配接受雷沙吉兰（剂量为每天 1 毫克或 2 毫克）治疗 72 周（早期开始组）或安慰剂治疗 36 周，然后接受雷沙吉兰（剂量为每天 1 毫克或 2 毫克）治疗 36 周（延迟开始组）。为了确定任一剂量的阳性结果，早期开始治疗组必须满足基于统一帕金森病评定量表（UPDRS，176分制，数字越高表明疾病越严重）的主要分析的三个分级终点中的每一个终点：在第12周和第36周之间的UPDRS评分变化率优于安慰剂，在基线和第72周之间的评分变化方面优于延迟开始治疗，以及在第 48 周和第 72 周之间的评分变化率方面，不劣于延迟开始治疗。结果每天 1 mg 剂量的雷沙吉兰早期开始治疗满足主要分析中的所有终点：第 12 周和第 36 周之间 UPDRS 评分（恶化率）的平均值 (+/- SE) 增加较小（早期开始组每周为 0.09 +/- 0.02 分，而早期开始组每周为 0.14 分）安慰剂组每周 +/- 0.01 分，P=0.01），基线和第 72 周之间的评分恶化程度较小（早期开始组为 2.82 +/- 0.53 分，延迟开始组为 4.52 +/- 0.56 分，P=0.02），并且两组之间在第 48 周和第 48 周之间 UPDRS 评分变化率方面具有非劣效性。 72（早期开始组每周 0.085 +/- 0.02 分，延迟开始组每周 0.085 +/- 0.02 分，P
BackgroundA therapy that slows disease progression is the major unmet need in Parkinson's disease.MethodsIn this double-blind trial, we examined the possibility that rasagiline has disease-modifying effects in Parkinson's disease. A total of 1176 subjects with untreated Parkinson's disease were randomly assigned to receive rasagiline (at a dose of either 1 mg or 2 mg per day) for 72 weeks (the early-start group) or placebo for 36 weeks followed by rasagiline (at a dose of either 1 mg or 2 mg per day) for 36 weeks (the delayed-start group). To determine a positive result with either dose, the early-start treatment group had to meet each of three hierarchical end points of the primary analysis based on the Unified Parkinson's Disease Rating Scale (UPDRS, a 176-point scale, with higher numbers indicating more severe disease): superiority to placebo in the rate of change in the UPDRS score between weeks 12 and 36, superiority to delayed-start treatment in the change in the score between baseline and week 72, and noninferiority to delayed-start treatment in the rate of change in the score between weeks 48 and 72.ResultsEarly-start treatment with rasagiline at a dose of 1 mg per day met all end points in the primary analysis: a smaller mean (+/- SE) increase ( rate of worsening) in the UPDRS score between weeks 12 and 36 (0.09 +/- 0.02 points per week in the early-start group vs. 0.14 +/- 0.01 points per week in the placebo group, P=0.01), less worsening in the score between baseline and week 72 (2.82 +/- 0.53 points in the early-start group vs. 4.52 +/- 0.56 points in the delayed-start group, P=0.02), and noninferiority between the two groups with respect to the rate of change in the UPDRS score between weeks 48 and 72 (0.085 +/- 0.02 points per week in the early-start group vs. 0.085 +/- 0.02 points per week in the delayed-start group, P