依拉环素与厄他培南对比治疗中国成人复杂性腹腔感染的疗效和安全性

Efficacy and safety of eravacycline versus ertapenem in the treatment of complicated intraperitoneal infection in Chinese adults:a multicenter,randomized,double-blind phaseⅢbridging trial

目的评估依拉环素在患有复杂性腹腔感染(cIAI)的中国成年住院患者中的疗效和安全性。方法采用多中心随机对照双盲Ⅲ期临床试验,cIAI患者被随机分配接受依拉环素(1.0mg/kg每12小时1次)或厄他培南(1g每24小时1次)静脉滴注,疗程5~14 d。分析治疗结束后不同时间点的主要与次要疗效,评估改良意向性治疗(MITT)人群、临床可评估(CE)人群和微生物学可评估(ME)人群的临床疗效及微生物疗效。分析比较两治疗组不同人群不同评价时间点的临床治愈率,计算基线病原菌阳性者微生物清除率。分析不良事件及与药物相关不良反应发生率。结果共144例至少接受过一剂研究药物的cIAI患者被纳入MITT人群,首剂用药后25~31天[疗效判断(TOC)访视时],依拉环素和厄他培南临床治愈率分别为77.8%(56/72)和90.3%(65/72)。在剔除<72h给药周期的受试者后,两组的临床治愈率分别为83.6%(56/67)和90.3%(65/72)。依拉环素组临床治愈率在TOC访视时的CE和ME人群分别为91.1%(51/56)和83.3%(25/30),厄他培南组分别为95.3%(61/64)和90.9%(30/33)。在TOC访视时,针对ME人群2种主要基线病原菌(大肠埃希菌和肺炎克雷伯菌),依拉环素组和厄他培南组对大肠埃希菌的微生物学疗效分别达到91.3%(21/23)和96.2%(25/26);对肺炎克雷伯菌的微生物学疗效分别为4/5和3/3。依拉环素组与厄他培南组治疗中出现的不良事件(TEAE)发生率相似,分别为75.0%对70.8%,绝大部分为轻、中度。依拉环素与药物相关的主要不良反应为输液部位静脉炎(9.7%,7/72)和输液部位疼痛(8.3%,6/72)。结论与厄他培南相似,依拉环素治疗cIAI具有良好的临床与微生物学疗效,且安全性良好。

Objective To evaluate the efficacy and safety of eravacycline in the treatment of complicated intra-abdominal infection(cIAI)in Chinese adult patients.Methods In this multicenter,randomized,double-blind phase III study,cIAI patients were randomly assigned to receive either eravacycline(1.0 mg/kg,q12h)or ertapenem(1 g,q24h)by intravenous infusion for 5 to 14 days.The primary and secondary efficacy endpoints included the clinical efficacy and microbiological efficacy in different populations,including modified intention-to-treat(MITT)population,clinically evaluable(CE)population,and microbiologically evaluable(ME)population,at different time points after treatment.Clinical cure rates at specific visits were summarized and compared between treatment groups in different populations.The microbial eradication rate was calculated for the patients with baseline pathogens.The incidence of adverse events(AE)and drug-related treatment emergent adverse event(TEAE)was analyzed by treatment group.Results A total of 144 patients with cIAI who received at least one dose of the study drug were included in the MITT population.The clinical cure rate was 77.8%(56/72)in eravacycline-treated patients and 90.3%(65/72)in ertapenem-treated patients at 25-31 days after the first dose(TOC visit).When the patients who received insufficient treatment(<72 hours)were excluded,the clinical cure rate was 83.6%(56/67)in eravacycline group and 90.3%(65/72)in ertapenem.For CE and ME patients,the clinical cure rate at TOC visit was 91.1%(51/56)and 83.3%(25/30)in eravacycline group,95.3%(61/64)and 90.9%(30/33)in ertapenem group.Eravacycline treatment achieved microbiological eradication rate of 91.3%(21/23)against Escherichia coli at TOC visit in micro-MITT population while ertapenem treatment resulted in a microbiological eradication rate of 96.2%(25/26).The microbiological efficacy of eravacycline and ertapenem against Klebsiella pneumoniae was 4/5 and 3/3,respectively.The incidence of TEAE was similar in eravacycline and ertapenem groups(75.0%vs.70.8%),most of which were mild or moderate.The AEs associated with eravacycline were mainly infusion site phlebitis(9.7%,7/72)and infusion site pain(8.3%,6/72).Conclusions Similar to ertapenem,eravacycline has good clinical and microbiological efficacy in treating cIAI.It is also safe and well-tolerated in the patients.