普拉克索（森福罗）和罗替戈汀透皮贴片治疗进展性帕金森病（Parkinson's
Efficacy of pramipexole and transdermal rotigotine in advanced Parkinson's disease: a double-blind, double-dummy, randomised controlled trial普拉克索（森福罗）和罗替戈汀透皮贴片治疗进展性帕金森病（Parkinson's disease，PD）的效果：一个双盲、双倍安慰剂的随机对照试验
Werner H Poewe MDa, , , Olivier Rascol MDb, Niall Quinn MDc, Eduardo Tolosa MDd, Wolfgang H Oertel MDe, Emilia Martignoni MDf, Markus Rupp MDg, Babak Boroojerdi MDg and on behalf of the SP 515 Investigators‡
aDepartment of Neurology, Innsbruck Medical University, Innsbruck, Austria
bService de Pharmacologie Clinique, Centre Hospitalier Universitaire, Toulouse, France
cInstitute of Neurology, University College London, London, UK
dNeurology Service, Hospital Clinic University, Barcelona, Spain
eDepartment of Neurology, Philipps University, Marburg, Germany
fUniversity of Piemonte Orientale, Novara and Unit of Neurorehabilitation and Movement Disorders, IRCCS S Maugeri, Scientific Institute of Veruno, Italy
gSchwarz Pharma, Monheim, Germany
作者及研究机构等从略
Summary
摘要
Background
背景
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.
在进展性帕金森病的治疗中，持续的给予多巴胺能药物并不能满足医疗需要。本试验，即普拉克索（森福罗）和罗替戈汀透皮贴片治疗进展性帕金森病（Parkinson's disease，PD）的临床疗效研究（CLEOPATRA-PD）的目的是评估在那些已经应用左旋多巴治疗并出现了症状波动中的疗效减退的帕金森病患者中，加用罗替戈汀，或安慰剂，或普拉克索来进行辅助治疗的疗效。
Methods
方法
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 ≥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.
在这个随机对照试验中，适合的参与者被随机的分别指定接受罗替戈汀（16mg/24h，敷贴），或普拉克索（4•5mg/d，口服），或安慰剂治疗6个月。最重要的效力变量是从基线到研究结束的总体“关”时相（由家庭日志评估）的绝对变化以及应答率（应答率定义为绝对“关”时相每天减少≥30%的患者比例）。分析基于临床治疗的目的。本试验已在美国国立卫生研究院临床试验数据库注册（ClinicalTrials.gov），注册号为NCT00244387。
Findings
结果
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.
204名患者随机接受罗替戈汀，201名接受普拉克索，101名接受安慰剂；427名（84％）完成了试验。每组中断试验的人数差不多；大多数都是因为副反应的发生（而中断试验）。罗替戈汀的平均剂量为12•95mg/24h（SD 3•54），普拉克索的平均剂量为3•1mg/d（1•24）。自基线起，罗替戈汀的关时相的平均绝对变化为−2•5h（SE 0•20），普拉克索的为−2•8h（0•20），安慰剂的为−0•9h（0•29）。与安慰剂相比，自基线起，罗替戈汀的关时相的平均绝对变化为−1•58h（95% CI −2•27 to −0•90；p<0•0001），普拉克索的为−1•94h（−2•63 to −1•25；p<0•0001）。普拉克索的应答率为67%（134/ 200），罗替戈汀的为59•7%（120/201），安慰剂的为35%（35/ 100）。
Interpretation
解读
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.
从绝对关时相的变化上看，罗替戈汀与普拉克索相比并没有劣势。治疗症状波动的帕金森病患者时，持续的给予罗替戈汀透皮贴片贴敷治疗（6个月以上的治疗）可达到与口服普拉克索治疗相似的疗效。
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