复方芩兰口服液治疗急性上呼吸道感染的Meta分析与试验序贯分析

Meta-analysis and trial sequential analysis of Compound Qinlan Oral Liquid in treatment of acute upper respiratory tract infection

系统评价复方芩兰口服液治疗急性上呼吸道感染的有效性与安全性。计算机检索中国知网(CNKI)、万方(Wanfang)、维普(VIP)、中国生物医学文献服务系统(SinoMed)、中国临床试验注册中心、ClinicalTrials.gov、Cochrane Library、PubMed、EMbase、Web of Science等,搜集有关复方芩兰口服液治疗急性上呼吸道感染的随机对照试验(RCT),并且辅以手工检索灰色文献。2位评价者独立筛选文献、提取资料并评价方法学质量,采用RevMan 5.4软件进行Meta分析、TSA 0.9.5.10 Beta软件进行试验序贯分析(TSA)、GRADE profiler 3.6.1软件进行证据质量评价。共纳入21篇RCTs,包含2651例患者,其中试验组1330例,对照组1321例。Meta分析结果显示,与单纯西医常规相比,复方芩兰口服液可提高总有效率(RR=1.15,95%CI[1.12,1.19],P<0.00001),且不会增加不良反应发生率(RR=0.77,95%CI[0.47,1.25],P=0.29)。亚组分析结果显示,①与单纯西医常规相比,复方芩兰口服液可提高总有效率(RR=1.10,95%CI[1.05,1.14],P<0.00001),减少症状改善时间(SMD=-0.76,95%CI[-1.02,-0.51],P<0.00001),但2组不良反应发生率差异无统计学意义(RR=1.16,95%CI[0.54,2.47],P=0.71);②与单纯西医常规相比,复方芩兰口服液+西医常规可提高总有效率(RR=1.20,95%CI[1.15,1.25],P<0.00001),降低中医证候积分(MD=-0.58,95%CI[-0.75,-0.41],P<0.00001),减少症状改善时间(SMD=-2.44,95%CI[-3.09,-1.80],P<0.00001),减少体征改善时间(MD=-2.57,95%CI[-4.11,-1.04],P=0.001),降低血清炎症因子水平(SMD=-2.16,95%CI[-2.61,-1.70],P<0.00001),改善呼吸功能指标(SMD=1.48,95%CI[1.00,1.96],P<0.00001),提高体液免疫水平(MD=0.94,95%CI[0.69,1.18],P<0.00001),但2组不良反应发生率差异无统计学意义(RR=0.57,95%CI[0.29,1.09],P=0.09)。TSA显示,总有效率的累积Z曲线穿过了传统界值和TSA界值,进一步肯定临床疗效。GRADE证据质量评价显示,上述结局指标的证据等级为低级或极低级,推荐强度为弱推荐。与单纯西医常规相比,复方芩兰口服液治疗急性上呼吸道感染可以提高总有效率,减少症状改善时间;复方芩兰口服液+西医常规治疗急性上呼吸道感染可以提高总有效率,改善患者症状和体征,改善炎症状况,改善呼吸功能以及提高机体免疫力。鉴于纳入研究的质量有限,上述结论仍需高质量RCT提供证据支持。

This study aims to evaluate the efficacy and safety of Compound Qinlan Oral Liquid in the treatment of acute upper respiratory tract infection.Computer-based online searching of CNKI,VIP,SinoMed,Wanfang,ChiCTR,ClinicalTrials.gov,Cochrane Library,PubMed,EMbase,and Web of Science was performed to retrieve the randomized controlled trial(RCT)regarding Compound Qinlan Oral Liquid in the treatment of acute upper respiratory tract infection.In addition,manual searching of gray literature was conducted.After two evaluators independently selected articles,extracted data,and evaluated the quality of methodology included in the studies,Meta-analysis was carried out in RevMan 5.4 and trial sequential analysis(TSA)in TSA 0.9.5.10 Beta.GRADE profiler 3.6.1 was employed to evaluate the evidence quality.A total of 21 RCTs were included in this study,involving 2651 patients(1330 patients in the observation group and 1321 patients in the control group).Meta-analysis showed that compared with conventional western medicine alone,Compound Qinlan Oral liquid improved the total response rate(RR=1.15,95%CI[1.12,1.19],P<0.00001)without increasing the incidence of adverse reactions(RR=0.77,95%CI[0.47,1.25],P=0.16).The results of subgroup analysis are described as follows:①Compared with conventional western medicine alone,Compound Qinlan Oral Liquid improved the total response rate(RR=1.10,95%CI[1.05,1.14],P<0.00001)and shortened the time to symptom relief(SMD=-0.76,95%CI[-1.02,-0.51],P<0.00001).There was no significant difference in the incidence of adverse reactions between the two groups(RR=1.16,95%CI[0.54,2.47],P=0.71).②Compared with conventional western medicine alone,Compound Qinlan Oral Liquid+conventional western medicine improved the total response rate(RR=1.20,95%CI[1.15,1.25],P<0.00001),decreased traditional Chinese medicine(TCM)syndrome scores(MD=-0.58,95%CI[-0.75,-0.41],P<0.00001),shortened the time to symptom relief(SMD=-2.44,95%CI[-3.09,-1.80],P<0.00001)and physical sign improvement(MD=-2.57,95%CI[-4.11,-1.04],P=0.001),lowered the serum levels of inflammatory cytokines(SMD=-2.16,95%CI[-2.61,-1.70],P<0.00001),improved respiratory function indicators(SMD=1.48,95%CI[1.00,1.96],P<0.00001),and enhanced the humoral immunity(MD=0.94,95%CI[0.69,1.18],P<0.00001).There was no significant difference in the incidence of adverse reactions between the two groups(RR=0.57,95%CI[0.29,1.09],P=0.09).TSA showed that the cumulative Z curve of total response rate crossed the traditional threshold and TSA threshold,further confirming the clinical efficacy of Compound Qinlan Oral Liquid.The GRADE graded the evidence of the above outcome indicators as low or extremely low,and yielded weak recommendation.Compared with conventional western medicine alone,Compound Qinlan Oral Liquid can improve the total effective rate and reduce the time to symptom relief.The combination of Compound Qinlan Oral Liquid and conventional western medicine can improve the total response rate,mitigate the symptoms and improve the physical signs,reduce inflammation,and improve respiratory function and immunity of the patients with acute upper respiratory tract infection.In view of the limited number and quality of the included studies,the above conclusions still require high-quality RCT to provide evidence support.