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

作　　者：倪俊[1] 陈会生 陈国芳[3] 纪勇[4] 易飞[5] 张卓伯[6] 杨弋[7] 吴晋[8] 蔡学礼[9] 邵蓓[10] 王剑锋[11] 刘雅芳[12] 耿德勤[13] 屈新辉[14] 李晓红[15] 魏琰[16] 丁建平[17] 吕桦[18] 黄一宁[19] 黄勇华[20] 肖波[21] 龚涛[22] 崔丽英[1] Ni Jun;Chen Huisheng;Chen Guofang;Ji Yong;Yi Fei;Zhang Zhuobo;Yang Yi;Wu Jin;Cai Xueli;Shao Bei;Wang Jianfeng;Liu Yafang;Geng Deqin;Qu Xinhui;Li Xiaohong;Wei Yan;Ding Jianping;Lyu Hua;Huang Yining;Huang Yonghua;Xiao Bo;Gong Tao;Cui Liying(Department of Neurology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences,Beijing 100730,China;Department of Neurology,General Hospital of Northern Theater Command,Shenyang 110016,China;Department of Neurology,Xuzhou Central Hospital,Xuzhou 221009,China;Department of Neurology,Tianjin Huanhu Hospital,Tianjin 300350,China;Department of Neurology,Pingxiang People′s Hospital,Pingxiang 337055,China;Department of Neurology,Fourth Affiliated Hospital of Harbin Medical University,Harbin 150001,China;Department of Neurology,First Hospital of Jilin University,Changchun 130021,China;Department of Neurology,Second Affiliated Hospital of Nanjing Medical University,Nanjing 210011,China;Department of Neurology,Lishui Municipal Central Hospital,Lishui 323000,China;Department of Neurology,First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,China;Department of Neurology,Dalian Municipal Central Hospital,Dalian 116033,China;Department of Neurology,Huangshi Central Hospital,Huangshi 435000,China;Department of Neurology,Affiliated Hospital of Xuzhou Medical University,Xuzhou 221006,China;Department of Neurology,Jiangxi Provincial People′s Hospital Affiliated to Nanchang University,Nanchang 330006,China;Department of Neurology,Jinan Central Hospital,Jinan 250013,China;Department of Neurology,Hengshui People′s Hospital(Harrison International Peace Hospital),Hengshui 100191,China;Department of Neurology,Xuanwu Hospital,Capital Medical University,Beijing 100053,China;Department of Neurology,Shaanxi Provincial People′s Hospital,Xi′an 710068,China;Department of Neurology,Peking University First Hospital,Beijing 100034,China;Department of Neurology,Seventh Medical Center of the Chinese People′s Liberation Army General Hospital,Beijing 100007,China;Dep

机构地区：[1]中国医学科学院北京协和医院神经科,北京100730 [2]北部战区总医院神经内科,沈阳110016 [3]徐州市中心医院神经内科,徐州221009 [4]天津市环湖医院神经内科,天津300350 [5]萍乡市人民医院神经内科,萍乡337055 [6]哈尔滨医科大学附属第四医院神经内科,哈尔滨150001 [7]吉林大学第一医院神经内科,长春130021 [8]南京医科大学第二附属医院神经内科,南京210011 [9]丽水市中心医院神经内科,丽水323000 [10]温州医科大学附属第一医院神经内科,温州325000 [11]大连市中心医院神经内科,大连116033 [12]黄石市中心医院神经内科,黄石435000 [13]徐州医学院附属医院神经内科,徐州221006 [14]江西省人民医院神经内科,南昌330006 [15]济南市中心医院神经内科,济南250013 [16]衡水市人民医院(哈励逊国际和平医院)神经内科,衡水100191 [17]首都医科大学宣武医院神经内科,北京100053 [18]陕西省人民医院神经内科,西安710068 [19]北京大学第一医院神经内科,北京100034 [20]解放军总医院第七医学中心神经内科,北京100007 [21]中南大学湘雅医院神经内科,长沙410008 [22]北京医院神经内科,北京100730

出　　处：《中华神经科杂志》2022年第5期474-480,共7页Chinese Journal of Neurology

摘　　要：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 differen

关 键 词：卒中 多中心研究 随机对照试验 运动障碍 马来酸桂哌齐特 亚组分析 

分 类 号：R743.3[医药卫生—神经病学与精神病学]