马来酸桂哌齐特注射液治疗合并明显肢体运动功能障碍的急性缺血性脑卒中患者的有效性和安全性

Efficacy and safety of cinepazide maleate injection in acute ischemic stroke patients with obvious motor function deficit

目的探究马来酸桂哌齐特注射液治疗合并肢体运动功能障碍的急性缺血性脑卒中患者的有效性和安全性。方法本研究为一项急性缺血性脑卒中的随机、双盲、多中心、安慰剂对照的Ⅳ期临床研究的亚组分析。该亚组分析共纳入基线期存在明显肢体运动功能障碍[定义为美国国立卫生研究院卒中量表(NIHSS)运动功能评分总和≥4分]的受试者812例,其中对马来酸桂哌齐特组给予马来酸桂哌齐特注射液静脉滴注治疗,对照组给予安慰剂治疗,治疗持续14 d,随访至90 d,同时对两组均给予基于指南的常规治疗。有效性指标包括用药后第90天改良Rankin量表(mRS)评分≤2分、mRS评分≤1分及Barthel指数<95的受试者比例,安全性结局通过监测生命体征、不良事件、实验室指标、心电图异常等进行评估。结果最终共732例受试者被纳入全分析集(马来酸桂哌齐特组361例,对照组371例),基线期NIHSS运动功能评分马来酸桂哌齐特组为(5.23±1.43)分,对照组(5.20±1.36)分。多因素Logistic回归分析结果显示:与对照组相比,马来酸桂哌齐特组用药后第90天mRS评分≤2分的患者比例显著高于对照组[56.0%(202/361)比44.2%(164/371),OR=0.60,95%CI 0.44~0.82,P=0.002];马来酸桂哌齐特组用药后第90天mRS评分≤1分的患者比例也高于对照组[43.3%(139/361)比35.2%(118/371),OR=0.69,95%CI 0.50~0.97,P=0.031];马来酸桂哌齐特组第90天Barthel指数<95的患者比例显著低于对照组[45.2%(145/361)比55.2%(185/371),OR=0.64,95%CI 0.46~0.88,P=0.007];治疗和随访期内马来酸桂哌齐特组的最常见不良事件发生率为50.4%(199/395),发生率最高的是便秘和肝功能异常,与对照组差异无统计学意义。结论马来酸桂哌齐特注射液能够显著改善合并明显肢体运动功能障碍的急性脑卒中患者的90 d神经功能预后和日常生活能力,减少残疾发生,且安全性良好。

Objective To confirm the efficacy and safety of cinepazide maleate injection in acute ischemic stroke patients with obvious motor function deficit.Methods This study is a subgroup analysis of multi-center,randomized,double-blind,placebo-controlled phaseⅣclinical trial.A total 812 patients of acute ischemic stroke with obvious limb motor deficit[motor function of limbs score in National Institutes of Health Stroke Scale(NIHSS)≥4]were enrolled in this subgroup analysis.Patients received either cinepazide maleate injection or placebo.The treatment period was 14 days and follow-up was 90 days.The efficacy endpoints included the proportions of patients with a modified Rankin Scale(mRS)score≤2,mRS score≤1 and Barthel Index<95 on day 90.Safety was evaluated by recording all adverse events,monitoring vital signs,laboratory parameters and electrocardiogram.Results A total of 732 patients were involved in the final efficacy analysis(361 in cinepazide maleate group and 371 in control group).The baseline limb motor function score of NIHSS was 5.23±1.43 in the cinepazide maleate group whereas 5.20±1.36 in the control group.Logistic regression analysis showed that following treatment for 90 days,the proportion of patients with a mRS score≤2 was significantly higher in the cinepazide maleate group than in the control group[56.0%(202/361)vs 44.2%(164/371),OR=0.60,95%CI 0.44-0.82,P=0.002].The proportion of patients with a mRS score≤1 was higher in the cinepazide maleate group than in the control group[43.3%(139/361)vs 35.2%(118/371),OR=0.69,95%CI 0.50-0.97,P=0.031].The proportion of patients with a Barthel Index<95 on day 90 was significantly lower in the cinepazide maleate group than in the control group[45.2%(145/361)vs 55.2%(185/371),OR=0.64,95%CI 0.46-0.88,P=0.007].During the treatment and follow-up period,the incidence of the most common adverse events in the cinepazide maleate group was 50.4%(199/395).Constipation and abnormal liver function were more common,but there were no statistically significant differences between the two groups.Conclusion Cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living,reducing disability,and promoting functional recovery and safe in patients with acute ischemic stroke with obvious limb motor deficit.