α-二氢麦角隐亭治疗初发帕金森病患者：一项多中心、随机、双盲、安慰剂对照研究的结果

Alpha-dihydroergocryptine in the treatment of de novo parkinsonian patients: results of a multicentre, randomized, double-blind, placebo-controlled study.

作者信息

Bergamasco B, Frattola L, Muratorio A, Piccoli F, Mailland F, Parnetti L

机构信息

First Neurological Clinic, San Giovanni Battista Hospital, University of Turin, Italy.

出版信息

Acta Neurol Scand. 2000 Jun;101(6):372-80. doi: 10.1034/j.1600-0404.2000.90295a.x.

DOI:10.1034/j.1600-0404.2000.90295a.x

PMID:10877152

Abstract

INTRODUCTION

A multicentre, randomized, double-blind, placebo-controlled, parallel group study was carried out in 123 patients suffering from never treated (de novo) idiopathic Parkinson's disease (PD). The aim of the study was to confirm the efficiency and safety of alpha-dihydroergocryptine (alpha-DHEC) given as monotherapy in the symptomatic treatment of PD. The total score of the Unified Parkinson's Disease Rating Scale (UPDRS) was identified as the efficacy target variable.

PATIENTS AND METHODS

Sixty-two patients (32 males, 30 females, mean age +/- SD 64 +/- 10) were randomized to alpha-dihydroergocryptine and 61 (30 males, 31 females, mean age 63.8 +/- 9.1) to placebo. According to the experimental design, a 18-month double-blind phase vs placebo was followed. Two interim analyses were planned both at the 3rd and 12th month of treatment, in order to avoid continuation on placebo, if clear differences between groups were found (stopping criterium: nominal significance level equal to 0.022 in the analysis of the target variable). Analysis of variance was performed both on the per protocol (PP) and intent-to-treat (ITT) sample.

RESULTS

The results on the first interim analysis showed significant differences between treatment groups of the UPDRS total score both in the ITT (115 patients, alpha-DHEC: No. 56; placebo: No. 59; P=0.019) and PP (96 patients, alpha-DHEC: No. 46; placebo: No. 50; P=0.001) sample, why the trial was stopped. At the time of stopping the trial, 73 patients (alpha-DHEC: No. 37; placebo: No. 36) had reached the 6-month observation visit; the analysis carried out on this subset of patients confirmed the efficacy of alpha-dihydroergocryptine in early PD and the correctness of the decision to stop. The incidence of adverse drug reactions (ADR) did not differ between alpha-dihydroergocryptine and placebo recipients, gastrointestinal complaints being the most frequent.

CONCLUSION

The results indicate that alpha-dihydroergocryptine is safe and effective in improving symptoms of de novo parkinsonian patients.

摘要

引言

对123例未经治疗（初发）的特发性帕金森病（PD）患者进行了一项多中心、随机、双盲、安慰剂对照的平行组研究。该研究的目的是确认α-二氢麦角隐亭（α-DHEC）单药治疗PD症状的有效性和安全性。统一帕金森病评定量表（UPDRS）的总分被确定为疗效目标变量。

患者与方法

62例患者（32例男性，30例女性，平均年龄±标准差64±10岁）被随机分配至α-二氢麦角隐亭组，61例（30例男性，31例女性，平均年龄63.8±9.1岁）被分配至安慰剂组。根据实验设计，随后进行了为期18个月的与安慰剂对照的双盲阶段。计划在治疗的第3个月和第12个月进行两次中期分析，以便在发现组间有明显差异时避免继续使用安慰剂（停止标准：目标变量分析中的名义显著性水平等于0.022）。对符合方案（PP）样本和意向性分析（ITT）样本均进行了方差分析。

结果

首次中期分析结果显示，在ITT（115例患者，α-DHEC组：56例；安慰剂组：59例；P = 0.019）和PP（96例患者，α-DHEC组：46例；安慰剂组：50例；P = 0.001）样本中，治疗组的UPDRS总分存在显著差异，因此试验停止。在试验停止时，73例患者（α-DHEC组：37例；安慰剂组：36例）已完成6个月的观察访视；对该亚组患者进行的分析证实了α-二氢麦角隐亭在早期PD中的疗效以及停止试验决定的正确性。α-二氢麦角隐亭组和安慰剂组的药物不良反应（ADR）发生率无差异，胃肠道不适最为常见。