Primary Outcomes From a Phase 3, Randomized, Double-Blind, Active-Controlled Trial of Surotomycin in Subjects With Clostridium difficile Infection
Primary Outcomes From a Phase 3, Randomized, Double-Blind, Active-Controlled Trial of Surotomycin in Subjects With Clostridium difficile Infection
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DOI：
10.1093/ofid/ofw275
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发表时间：
2017-01-01
影响因子：
4.2
通讯作者：
Murata, Yoshihiko
中科院分区：
文献类型：
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作者：
Boix, Vicente;Fedorak, Richard N.;Murata, Yoshihiko
背景虽然艰难梭菌感染（CDI）的发病率正在增加，但可用的CDI治疗选择在治疗后的持续反应方面有限。这项3期试验评估了一种新型杀菌性环脂肽surotomycin与口服万古霉素相比在CDI患者中的疗效和安全性。在这项随机、双盲、活性对照、多中心、国际试验中，通过阳性毒素结果证实的CDI受试者随机接受舒罗霉素（250 mg，每日2次）或万古霉素（125 mg，每日4次）口服治疗10天。主要终点是治疗结束时的临床应答和对surotomycin安全性的评价。关键次要终点为随时间推移的临床应答和30- 40天随访期内的持续临床应答。随访期间艰难梭菌感染复发和腹泻消退时间也进行了分析。总共有570例受试者接受了随机化并确认了CDI; 290例受试者接受了舒托霉素治疗，280例受试者接受了万古霉素治疗。治疗结束时的舒罗托霉素临床治愈率（瑞托霉素/万古霉素：79.0%/83.6%;差异为-4.6%; 95%置信区间，-11.0至1.9]），随时间推移的临床应答（分层对数秩检验，P = 0.832）和试验结束时的持续临床应答（第40-50天）（60.6%/61.4%;差异为-0.8%; 95% CI，-8.8至7.1），与万古霉素相比不符合非劣效性或优效性标准。两种治疗一般耐受良好。在本试验的主要终点和关键次要终点方面，舒罗托霉素不符合相对于万古霉素的非劣效性标准。
Background. Although the incidence of Clostridium difficile infection (CDI) is increasing, available CDI treatment options are limited in terms of sustained response after treatment. This phase 3 trial assessed the efficacy and safety of surotomycin, a novel bactericidal cyclic lipopeptide, versus oral vancomycin in subjects with CDI.Methods. In this randomized, double-blind, active-controlled, multicenter, international trial, subjects with CDI confirmed by a positive toxin result were randomized to receive surotomycin (250 mg twice daily) or vancomycin (125 mg 4 times daily) orally for 10 days. The primary endpoints were clinical response at end of treatment and evaluation of surotomycin safety. The key secondary endpoints were clinical response over time and sustained clinical response through a 30-to 40-day follow-up period. Clostridium difficile infection recurrence during follow-up and time to diarrhea resolution were also analyzed.Results. In total, 570 subjects were randomized and had confirmed CDI; 290 subjects received surotomycin and 280 subjects received vancomycin. Surotomycin clinical cure rates at end of treatment (surotomycin/vancomycin: 79.0%/83.6%; difference of -4.6%; 95% confidence interval, -11.0 to 1.9]), clinical response over time (stratified log-rank test, P =.832), and sustained clinical response at end of trial (Day 40-50) (60.6%/61.4%; difference of -0.8%; 95% CI, -8.8 to 7.1) in the microbiological modified intent to treat population did not meet noninferiority or superiority criteria versus vancomycin. Both treatments were generally well tolerated.Conclusions. Surotomycin failed to meet the criteria for noninferiority versus vancomycin for the primary and key secondary endpoints in this trial.