奥拉西坦注射液治疗急性缺血性脑卒中的多中心随机对照临床试验

Oxiracetam injection in the treatment of acute cerebral infarction:a multicenter and randomized controlled trial

目的评价进口奥拉西坦注射液与国产奥拉西坦注射液治疗急性缺血性脑卒中的有效性和安全性。方法由四川大学华西医院为负责单位,广西壮族自治区人民医院、桂林医学院附属医院、吉林省人民医院神经内科、昆明医科大学第二附属医院、兰州大学第一医院、四川省人民医院、苏州大学附属第一医院、天津中医药大学第一附属医院、重庆三峡中心医院、苏州大学附属第二医院为参加单位,于2013年3月—2014年7月对进口奥拉西坦注射液(韩国高丽制药株式会社生产)与国产奥拉西坦注射液(商品名:欧兰同,哈尔滨三联药业有限公司生产)治疗急性缺血性脑卒中有效性和安全性进行随机盲法、阳性药对照、多中心临床试验。将240例急性缺血性脑卒中患者随机分为试验组(基础治疗+进口奥拉西坦注射液组)和对照组(基础治疗+国产奥拉西坦注射液组),每组各120例。分别于治疗1、2周后和治疗结束后12周随访。最终纳入符合方案集分析的共200例,其中试验组101例,对照组99例。分别使用美国国立卫生研究院卒中量表(National Institute of Health Stroke Scale,NHISS)、改良Rankin量表(Modified Rankin Scale,m RS)和巴氏指数(Barthe Index,BI)来评估受试者的神经功能缺损程度、病残程度、生活质量和治疗有效率。安全性评估指标包括不良事件和生命体征。结果试验组和对照组的NHISS评分在治疗前分别为(7.46±1.99)、(7.20±2.47)分,治疗1周后分别为(5.81±2.30)、(5.54±2.58)分,治疗2周后分别为(3.93±2.40)、(3.79±2.39)分,治疗结束后12周分别为(1.85±1.63)、(2.08±2.01)分,两组比较差异均无统计学意义(P>0.05);两组在治疗1、2周后和治疗结束后12周的m RS分级、BI比较差异均无统计学意义(P>0.05);治疗后各时点的NHISS评分、m RS分级、BI与该组治疗前比较差异均有统计学意义(P<0.05)。两组各时点的治疗有效率比较差异均无统计学意义(P>0.05)。试验组共50例(41.66%)发生111例次(92.50%)不良事件,对照组共61例(50.83%)发生145例次(120.83%)不良事件,两组比较差异无统计学意义,且绝大多数不良反应为轻度。两组患者治疗2周后的生命指征比较差异均无统计学意义(P>0.05)。结论进口奥拉西坦注射液与国产奥拉西坦注射液治疗急性缺血性脑卒中的疗效无明显差异,且安全性均良好。

Objective To evaluate the clinical efficacy and safety of imported and domestic oxiracetam injection in the treatment of acute cerebral infarction. Methods Between March 2013 and July 2014, a multicenter randomized blind controlled clinical study was conducted to learn the clinical efficacy and safety of imported oxiracetam injection （produced by Korea Pharmaceutical Corporation） and domestic oxiracetam injection （named as Oulantong, produced by Harbin Medisan Pharmaceutical Co., Ltd） in the treatment of acute cerebral infarction. West China Hospital of Sichuan University was in charge of the study, and the participants included the People’s Hospital of Guangxi Zhuang Autonomous Region, Affiliated Hospital of Guilin Medical University, Department of Neurology of Jilin Provincial People’s Hospital, the Second Affiliated Hospital of Kunming Medical University, the First Hospital of Lanzhou University, Sichuan Academy of Medical Sciences ＆ Sichuan Provincial People’s Hospital, the First Affiliated Hospital of Soochow University, the First Affiliated Hospital of Tianjin University of TCM, Chongqing Three Gorges Central Hospital, and the Second Affiliated Hospital of Soochow University. A total of 240 patients with acute cerebral infarction were randomly divided into trial group （basic treatment plus imported oxiracetam injection） and control group （basic treatment plus domestic oxiracetam） with 120 patients in each. Follow-up was conducted 1 week, 2 weeks and 12 weeks after treatment. Finally, 200 patients consistent with the study criteria were included, including 101 in the trial group and 99 in the control group. National Institute of Health Stroke Scale （NHISS）, Modified Rankin Scale （mRS） and Barthel Index （BI） were used to evaluate patients’ neurologic impairment, disability degree, life quality and treatment effective rate. Safety indexes included adverse events and life vital signs. Results NHISS scores of the trial group and the control group were respectively （7.46±1.99） and （7.20±2.47） points before the treatment, （5.81±2.30） and （5.54±2.58） points one week after the treatment, （3.93±2.40） and （3.79±2.39） points two weeks after the treatment, （1.85±1.63） and （2.08±2.01） points 12 weeks after the treatment. There was no significant difference between the two groups at all time points （P〉0.05）. BI and mRS grading were not significantly different between the two groups at all time points after the treatment （P〉0.05）. NHISS score, mRS grading and BI at each time point after the treatment were significantly different from those before the treatment （P〈0.05）. No significant differences were found between the two groups in the treatment effective rate at each time point （P〉0.05）. Fifty patients （41.66%） in the trial group had 111 adverse events （92.50%）, and 61 （50.83%） in the control group had 145 adverse events （120.83%）. There was no significant difference between the two groups （P〉0.05）. Moreover, most of the adverse reactions were at a mild degree. Life vital signs two weeks after the treatment were not significantly different between the two groups, either （P〉0.05）. Conclusion Imported oxiracetam injection is of similar efficacy and safety with domestic Oulantong injection in the treatment of acute cerebral infarction.