Poewe Werner H, Rascol Olivier, Quinn Niall, Tolosa Eduardo, Oertel Wolfgang H, Martignoni Emilia, Rupp Markus, Boroojerdi Babak
Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
Lancet Neurol. 2007 Jun;6(6):513-20. doi: 10.1016/S1474-4422(07)70108-4.
Continuous dopaminergic drug delivery is an unmet medical need in advanced Parkinson's disease. The aim of this trial-Clinical Efficacy of Pramipexole And Transdermal Rotigotine in Advanced PD (CLEOPATRA-PD)-was to assess the efficacy of adjunct treatment with rotigotine in comparison with placebo and with pramipexole in levodopa-treated patients with advanced Parkinson's disease and wearing-off type motor fluctuations.
In this randomised controlled trial, eligible participants were randomly assigned to receive either rotigotine (up to 16 mg/24 h as a transdermal patch), pramipexole (up to 4.5 mg/day orally), or placebo for 6 months. Primary efficacy variables were absolute change in total hours "off" (assessed by home diaries) from baseline to end of study and responder rate (defined as the proportion of patients with >or=30% reduction in absolute off time per day). Analyses were done by intention to treat. This trial is registered with the US National Institutes of Health clinical trials database (ClinicalTrials.gov), number NCT00244387.
204 patients were randomly assigned to receive rotigotine, 201 to receive pramipexole, and 101 to receive placebo; 427 (84%) completed the trial. The number of discontinuations in each group was similar; most were for adverse events. The mean dose of rotigotine was 12.95 mg/24 h (SD 3.54), the mean dose of pramipexole was 3.1 mg/day (1.24). Mean absolute change in off time from baseline was -2.5 h (SE 0.20) with rotigotine, -2.8 h (0.20) with pramipexole, and -0.9 h (0.29) with placebo. The absolute change in off time from baseline compared with placebo was -1.58 h (95% CI -2.27 to -0.90; p<0.0001) for rotigotine and -1.94 h (-2.63 to -1.25; p<0.0001) for pramipexole. Responder rates were 67% (134 of 200 patients) for pramipexole, 59.7% (120 of 201 patients) for rotigotine, and 35% (35 of 100 patients) for placebo.
In terms of change in absolute off time, rotigotine was non-inferior to pramipexole. Continuous delivery of rotigotine as transdermal patches could offer similar efficacy to oral pramipexole in patients with fluctuating Parkinson's disease over 6 months of treatment.
持续多巴胺能药物给药是晚期帕金森病尚未满足的医疗需求。本试验——普拉克索与透皮罗替戈汀在晚期帕金森病中的临床疗效（CLEOPATRA - PD）——旨在评估罗替戈汀辅助治疗与安慰剂以及与普拉克索相比，在接受左旋多巴治疗的晚期帕金森病且有剂末型运动波动患者中的疗效。
在这项随机对照试验中，符合条件的参与者被随机分配接受罗替戈汀（高达16毫克/24小时，通过透皮贴剂给药）、普拉克索（高达4.5毫克/天，口服）或安慰剂，为期6个月。主要疗效变量是从基线到研究结束时“关”期总时长的绝对变化（通过家庭日记评估）以及应答率（定义为每天绝对“关”期时间减少≥30%的患者比例）。分析采用意向性治疗。本试验已在美国国立卫生研究院临床试验数据库（ClinicalTrials.gov）注册，编号为NCT00244387。
随机分配204例患者接受罗替戈汀，201例接受普拉克索，101例接受安慰剂；427例（84%）完成试验。每组停药人数相似；大多数是因为不良事件。罗替戈汀的平均剂量为12.95毫克/24小时（标准差3.54），普拉克索的平均剂量为3.1毫克/天（1.24）。罗替戈汀组从基线到“关”期时间的平均绝对变化为 - 2.5小时（标准误0.20），普拉克索组为 - 2.8小时（0.20），安慰剂组为 - 0.9小时（0.29）。与安慰剂相比，罗替戈汀组从基线到“关”期时间的绝对变化为 - 1.58小时（95%置信区间 - 2.27至 - 0.90；p<0.0001），普拉克索组为 - 1.94小时（ - 2.63至 - 1.25；p<0.0001）。应答率方面，普拉克索为67%（200例患者中的134例），罗替戈汀为59.7%（201例患者中的120例），安慰剂为35%（100例患者中的35例）。
就绝对“关”期时间变化而言，罗替戈汀不劣于普拉克索。在6个月的治疗期内，对于帕金森病症状波动的患者，透皮贴剂持续给药的罗替戈汀与口服普拉克索疗效相似。
