国产A型肉毒毒素治疗膀胱过度活动症的有效性和安全性:多中心、随机、双盲、安慰剂平行对照研究  

Efficacy and safety study of Chinese botulinum toxin A 100U in patients with overactive bladder:a prospective,multicenter,double-blind and randomized controlled trial

作　　者：廖利民[1] 丛惠伶[1] 徐智慧[2] 李恩惠[2] 翁志梁[3] 江海红[3] 刘犇[4] 黄啸[4] 夏术阶[5] 文伟[5] 吴娟[1] 施国伟 王洋 李培军[7] 余洋[7] 方祖军 郑捷 田野[9] 尚浩东 李汉忠[10] 黄钟明[10] 周利群[11] 肖云翔[11] 张耀光[12] 王建龙[12] 张小东[13] 张鹏[13] 王东文[14] 张旭辉[14] 谢克基[15] 王斌[15] 马潞林[16] 田晓军[16] 陈立军 董金凯 Liao Limin;Cong Huiling;Xu Zhihui;Li Enhui;Weng Zhiliang;Jiang Haihong;Liu Ben;Huang Xiao;Xia Shujie;Wen Wei;Wu Juan;Shi Guowei;Wang Yang;Li Peijun;Yu Yang;Fang Zujun;Zheng Jie;Tian Ye;Shang Haodong;Li Hanzhong;Huang Zhongming;Zhou Liqun;Xiao Yunxiang;Zhang Yaoguang;Wang Jianlong;Zhang Xiaodong;Zhang Peng;Wang Dongwen;Zhang Xuhui;Xie Keji;Wang Bin;Ma Lulin;Tian Xiaojun;Chen Lijun;Dong Jinkai(Department of Urology,China Rehabilitation Research Centre,School of Rehabilitation,Capital Medical University,Beijing 100068,China;Department of Urology,Zhejiang Provincial People's Hospital,Hangzhou 310014,China;Department of Urology,First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,China;Department of Urology,First Affiliated Hospital of Zhejiang University School of Medicine,Hangzhou 310003,China;Department of Urology,Shanghai First People's Hospital,Shanghai 200080,China;Department of Urology,Shanghai Fifth People's Hospital,Shanghai 310000,China;Department of Urology,Ningxia Medical University General Hospital,Xining 750004,China;Department of Urology,Huashan Hospital,Fudan University,Shanghai 200040,China1;Department of Urology,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China;Department of Urology,Peking Union Hospital,Chinese Academy of Medical Sciences,Beijing 100730,China;Department of Urology,Peking University First Hospital,Beijing 100034,China;Department of Urology,Beijing Hospital,Beijing 100730,China;Department of Urology,Beijing Chaoyang Hospital,Capital Medical University,Beijing 100020,China;Department of Urology,First Hospital of Shanxi Medical University,Taiyuan 030012,China;Department of Urology,Guangzhou First People's Hospital,Guangzhou 510180,China;Department of Urology,Third Hospital of Peking University,Beijing 100191,China;Department of Urology,Fifth Medical Center of PLA General Hospital,Beijing 100039,China)

机构地区：[1]中国康复研究中心北京博爱医院泌尿外科首都医科大学康复医学院,北京100068 [2]浙江省人民医院泌尿外科,杭州310014 [3]温州医科大学附属第一医院泌尿外科,温州325000 [4]浙江大学医学院附属第一医院泌尿外科,杭州310003 [5]上海市第一人民医院泌尿外科,200080 [6]上海市第五人民医院泌尿外科,310000 [7]宁夏医科大学总医院泌尿外科,西宁750004 [8]复旦大学附属华山医院泌尿外科,上海200040 [9]首都医科大学附属北京友谊医院泌尿外科,北京100050 [10]中国医学科学院北京协和医院泌尿外科,北京100730 [11]北京大学第一医院泌尿外科,100034 [12]北京医院泌尿外科,100730 [13]首都医科大学附属北京朝阳医院泌尿外科,北京100020 [14]山西医科大学第一医院泌尿外科,太原030012 [15]广州市第一人民医院泌尿外科,广州510180 [16]北京大学第三医院泌尿外科,100191 [17]解放军总医院第五医学中心泌尿外科,北京100039

出　　处：《中华泌尿外科杂志》2021年第6期414-422,共9页Chinese Journal of Urology

摘　　要：目的探讨国产A型肉毒毒素(BTX-A)100 U注射剂量治疗膀胱过度活动症(OAB)的疗效和安全性。方法2016年4月至2018年12月对17家三甲医院的OAB患者进行试验。本研究分为核心试验阶段和扩展试验阶段。核心试验阶段采用前瞻性、多中心、随机、双盲、安慰剂平行对照的试验方法进行研究。纳入标准:年龄18~75岁;口服抗胆碱能药物疗效不满意或不耐受;可自主排尿的患者。排除标准:过敏体质;严重的心、肾、肝脏疾病;6个月内接受过任何BTX制剂治疗;伴泌尿系感染、泌尿系结石、泌尿系肿瘤;糖尿病;有出血倾向者。按2∶1的比例将OAB患者分为试验组和安慰剂对照组。试验组将100 U的国产BTX-A用10 ml生理盐水复溶,于膀胱镜下分20个点注射入逼尿肌,注射位点分布于膀胱底部(5点)、膀胱三角区(3点)、两侧壁(各5点)及顶部(2点),避开膀胱颈,注射深度为黏膜下肌层。对照组同法注射不含注射用BTX-A的安慰剂。比较两组治疗前与治疗后2、6、12周的每24小时平均排尿次数、平均每日尿急次数和评分、平均每日尿失禁次数、平均每次排尿量、膀胱过度活动症症状评分(OABSS)及生活质量评分变化情况。主要疗效指标为第6周随访时排尿次数较基线的变化情况。次要疗效指标为2、12周两组每24小时平均排尿次数较基线的变化情况,以及2、6、12周两组患者OABSS和生活质量评分、平均每日尿急次数和评分、平均每日尿失禁次数、平均每次排尿量较基线的变化情况。治疗后12周记录不良事件。扩展试验阶段纳入标准:①受试者自愿接受BTX-A治疗;②第12周评估时,排尿日记显示每24小时排尿次数较基线下降<50%。进入扩展试验阶段两组患者在"第12周访视"时均注射1次100 U的国产BTX-A,然后随访12周,随访指标同核心试验阶段。结果本研究共纳入216例,试验组144例,对照组72例。试验组和对照组的年�Objective To assess the efficacy and safety of 100 units of botulinum toxin A(BTX-A)intradetrusor injection in patients with overactive bladder.Methods From April 2016 to December 2018,17 tertiary hospitals were selected to participate in this prospective,multicenter,randomized,double-blind,placebo-controlled study.Two phases of study were conducted:the primary phase and the extended phase.This study enrolled patients aged 18 to 75 years who had been inadequately managed by anticholinergic therapy(insufficient efficacy or intolerable side effects)and had spontaneous voiding with overactive bladder.Exclusion criteria included patients with severe cardiac,renal and hepatic disorders,patients with previous botulinum toxin treatment for 6 months or allergic to BTX-A,patients with urinary tract infections,patients with urinary stones,urinary tract tumors,diabetes mellitus,and bleeding tendency.Eligible patients were randomly assigned to BTX-A group and placebo control group in a ratio of 2∶1.Two groups of patients received 20 intradetrusor injections of BTX-A 100U or placebo at the depth of the submucosal muscle layer respectively under cystoscope,including 5 injections at the base of the bladder,3 injections to the bladder triangle,5 injections each to the left and right walls and 2 injections to the top,sparing the bladder neck.As a placebo control group,patients received same volume of placebo containing no BTX-A and only adjuvant freeze-dried preparations for injection with the same method.A combination of gelatin,sucrose,and dextran served as adjuvants.Average micturition times per 24 hours,urinary incontinence(UI)episodes per day,average micturition volume per day,OAB symptom score(OABSS),and quality of life(QOL)score were recorded at baseline and the 2nd,6th and 12th week after treatment.The primary efficacy endpoint was the change from baseline in the average micturition times per 24 hours at the 6th week after treatment.The secondary efficacy endpoints included the change from baseline in the average mictur

关 键 词：膀胱 过度活动性 膀胱过度活动症 国产 A型肉毒毒素 治疗 

分 类 号：R694.5[医药卫生—泌尿科学]