雾化吸入重组人干扰素α1b治疗小儿呼吸道合胞病毒下呼吸道感染的有效性和安全性多中心、随机、双盲、安慰剂对照Ⅲ期临床研究  

The efficacy and safety of nebulized inhalation of recombinant human interferonα1b in the treatment of pediatric respiratory syncytial viral associated lower respiratory tract infections:a multicenter,randomized,double-blind,placebo-controlled phase Ⅲ clinical study

作　　者：刘小会[1] 徐保平[1] 尚云晓[2] 张晗[2] 张振坤 林广裕[4] 殷菊[1] 崔爱华[5] 张国成 石曌玲 高立伟[1] 蒋春明[7] 边俊梅 黄永建[9] 张蓉芳[10] 刘小梅[1] 杨晓庆 汤昱 钟礼立[13] 乔红梅[14] 郝创利[15] 王宇清[15] 李渠北[16] 曹玲[17] 杨运刚[18] 路苓[19] 林荣军[20] 孙兴珍[21] 周薇[22] 陈强[23] 邓继岿[24] 郑跃杰[25] 赵琳[26] 艾涛 刘小红[28] 陆小霞 姜宁 李明[31] Liu Xiaohui;Xu Baoping;Shang Yunxiao;Zhang Han;Zhang Zhenkun;Lin Guangyu;Yin Ju;Cui Aihua;Zhang Guocheng;Shi Zhaoling;Gao Liwei;Jiang Chunming;Bian Junmei;Huang Yongjian;Zhang Rongfang;Liu Xiaomei;Yang Xiaoqing;Tang Yu;Zhong Lili;Qiao Hongmei;Hao Chuangli;Wang Yuqing;Li Qubei;Cao Ling;Yang Yungang;Lu Ling;Lin Rongjun;Sun Xingzhen;Zhou Wei;Chen Qiang;Deng Jikui;Zheng Yuejie;Zhao Lin;Ai Tao;Liu Xiaohong;Lu Xiaoxia;Jiang Ning;Li Ming(Department of Respiratory,Beijing Children′s Hospital,Capital Medical University,National Clinical Research Center of Respiratory Diseases,National Center for Children′s Health,Beijing 100045,China;Department of Pediatrics,Shengjing Hospital of China Medical University,Shenyang 110004,China;Department of Respiratory Medicine,Xuzhou Children′s Hospital,Xuzhou 221002,China;Pediatrics Department,the Second Affiliated Hospital of Shantou University Medical College,Shantou 515041,China;Department of Pediatrics,Liaocheng People′s Hospital,Liaocheng 252000,China;Department of Pediatrics,the Second Affiliated Hospital of Shaanxi University of Chinese Medicine(Xixian New District Central Hospital),Xianyang 712046,China;Department of Pediatrics,Hangzhou First People′s Hospital,Hangzhou 310003,China;Department of Pediatrics,Wuhan Third Hospital,Wuhan 430070,China;Department of Pediatrics,Tongji Hospital,Tongji Medical College of HUST,Wuhan 430030,China;Allergy Department,Gansu Provincial Maternal and Child Health Hospital,Lanzhou 730050,China;Department of Pediatrics,Women and Children′s Hospital Affi-liated to Xiamen University,Xiamen 361003,China;Department of Respiratory Medicine,Henan Provincial Children′s Hospital,Zhengzhou 450018,China;Department of Pediatric Respiratory Medicine,People′s Hospital of Hunan Province,Changsha 410002,China;Department of Pediatric Respiratory Medicine,Bethune First Hospital of Jilin University,Changchun 130021,China;Department of Respiratory Medicine,Children′s Hospital of Soochow University,Suzhou 215025,China;Department of Respiratory Medicin

机构地区：[1]国家儿童医学中心,国家呼吸系统疾病临床医学研究中心,首都医科大学附属北京儿童医院呼吸中心,北京100045 [2]中国医科大学附属盛京医院儿科,沈阳110004 [3]徐州市儿童医院呼吸内科,徐州221002 [4]汕头大学医学院第二附属医院儿科,汕头515041 [5]聊城市人民医院儿科,聊城252000 [6]陕西中医药大学第二附属医院(西咸新区中心医院),咸阳712046 [7]杭州市第一人民医院儿科,杭州310003 [8]武汉市第三医院儿科,武汉430070 [9]华中科技大学同济医学院附属同济医院儿科,武汉430030 [10]甘肃省妇幼保健院过敏反应科,兰州730050 [11]厦门大学附属妇女儿童医院儿内科,厦门361003 [12]河南省儿童医院呼吸科,郑州450018 [13]湖南省人民医院小儿呼吸科,长沙410002 [14]吉林大学白求恩第一医院小儿呼吸科,长春130021 [15]苏州大学附属儿童医院呼吸科,苏州215025 [16]重庆医科大学附属儿童医院呼吸科,重庆400013 [17]首都儿科研究所附属儿童医院呼吸科,北京100020 [18]厦门大学附属第一医院儿科,厦门361003 [19]枣庄市立医院儿科,枣庄277102 [20]青岛大学附属医院综合儿科,青岛266035 [21]南京医科大学附属淮安第一医院儿科,淮安223300 [22]北京大学第三医院儿科,北京100083 [23]江西省儿童医院呼吸内科,南昌330006 [24]深圳市儿童医院感染科,深圳518038 [25]深圳市儿童医院呼吸科,深圳518038 [26]昆明医科大学第二附属医院儿科,昆明650101 [27]成都妇女儿童中心医院儿童呼吸科,成都610072 [28]西安交通大学第一附属医院儿科,西安710061 [29]华中科技大学同济医学院附属武汉儿童医院呼吸内科,武汉430015 [30]山东省妇幼保健院儿科,济南250014 [31]昆明市儿童医院呼吸内科,昆明650034

出　　处：《中华实用儿科临床杂志》2025年第3期180-186,共7页Chinese Journal of Applied Clinical Pediatrics

基　　金：北京市高层次公共卫生技术人才培养计划项目(2022-2-023)。

摘　　要：目的评价重组人干扰素α1b注射液雾化吸入治疗小儿呼吸道合胞病毒(RSV)下呼吸道感染(肺炎和毛细支气管炎)的有效性和安全性。方法采用随机、双盲、平行、安慰剂对照的加载设计方法。选择2021年2月至2022年12月来自首都医科大学附属北京儿童医院等30家临床研究中心的发病72 h内的2月龄至5岁的RSV肺炎或毛细支气管炎患儿,按1∶1分层区组随机分为2组,2组均予止咳、平喘、祛痰、退热、氧疗等基础治疗,试验组加用雾化吸入重组人干扰素α1b注射液,2.0μg/(kg·次),2次/d;对照组雾化吸入安慰剂,2次/d。通过临床症状、体征的消失时间等指标评价临床疗效,采用Kaplan-Meier方法计算临床症状和体征中位消失时间及其95%CI,采用Log-rank检验比较组间差异。通过不良反应发生情况和实验室检查评价安全性,采用χ^(2)检验比较组间差异。结果试验组和对照组分别纳入123例和122例患儿,治疗后试验组5项临床症状、体征[气促、喘息、呼吸困难(三凹征)、经皮血氧饱和度下降、精神状况异常]均消失的时间短于对照组[2.7 d(95%CI:1.9~3.0 d)比2.9 d(95%CI:2.6~3.6 d),P=0.027]。试验组呼吸困难(三凹征)的改善尤其明显,给药第1天三凹征缓解率即达50.0%(0,100%),与对照组[0(0,50.0%)]比较,差异有统计学意义(Z=2.002,P=0.025);三凹征的消失时间较对照组缩短近1 d[1.0 d(95%CI:0.7~1.7 d)比1.8 d(95%CI:1.0~2.5 d),P=0.046]。在住院时间[6.0(5.0,8.0)d比6.5(5.0,8.0)d,Z=0.675,P=0.500]、氧疗持续时间[32.0(14.0,96.3)h比39.0(24.0,83.2)h,Z=0.094,P=0.925]、治疗期间临床症状恢复率[(105/106,99.1%)比(96/101,95.0%)]及复发率[(0/106,0)比(2/101,2.0%)]等方面,虽然上述指标组间比较差异均无统计学意义(均P>0.05),但试验组均显示出临床获益的趋势。病毒定量检测结果显示,治疗后2组RSV病毒载量较治疗前均呈下降趋势,治疗2 d后试验组和对照组RSV载量较基线下降速率Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon(IFN)α1b injection in the treatment of respiratory syncytial virus(RSV)associated lower respiratory tract infections(pneumonia and bronchiolitis)in children.Methods:A randomized,double-blind,parallel,placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital,Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control,asthma relieving,expectorant treatment,fever reduction,oxygen therapy,etc.The experimental group received additional nebulized inhalation of IFNα1b injection at a dose of 2.0μg/(kg·time),twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs,and the Kaplan-Meier method was used to calculate the median and 95%CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests,and the Chi-square test was used to analyze the difference between groups.Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs[including shortness of breath,wheezing,dyspnea(visible retractions),decreased transcutaneous oxygen saturation,and abnormal mental state]in the experimental group after treatment were slightly shortened than those in the control group[2.7 d(95%CI:1.9-3.0 d)]vs.[2.9 d(95%CI:2.6-3.6 d),P=0.027].The improvement in dyspnea(retractions)was especially pronounced in the experimental group,with a r

关 键 词：重组人干扰素Α1B 雾化吸入 呼吸道合胞病毒 下呼吸道感染 

分 类 号：R72[医药卫生—儿科]