厄他培南对比哌拉西林/他唑巴坦治疗中国糖尿病足感染：一项 3 期、多中心、随机、双盲、阳性药物对照、非劣效性临床试验。

Ertapenem versus piperacillin/tazobactam for diabetic foot infections in China: a Phase 3, multicentre, randomized, double-blind, active-controlled, non-inferiority trial.

机构信息

The 306th Hospital, Beijing 100101, China

West China Hospital, Sichuan University, Chengdu, China.

出版信息

J Antimicrob Chemother. 2016 Jun;71(6):1688-96. doi: 10.1093/jac/dkw004. Epub 2016 Feb 16.

DOI:10.1093/jac/dkw004

PMID:26888908

Abstract

OBJECTIVES

Few randomized controlled studies have compared antibiotic regimens against diabetic foot infections (DFIs) in Chinese patients. We evaluated the efficacy and safety of ertapenem versus piperacillin/tazobactam for the treatment of DFIs in Chinese patients.

METHODS

Patients with moderate to severe DFIs requiring parenteral antibiotics were randomized in a 1 : 1 ratio to receive ertapenem (1.0 g once daily) or piperacillin/tazobactam (4.5 g every 8 h) by 30 min intravenous (iv) infusions for ≥5 days. The primary outcome was favourable clinical response at discontinuation of iv therapy (DCIV). An evaluable-patient population was identified for primary analysis of non-inferiority at -15%. Safety was assessed. ClinicalTrials.gov: NCT01370616.

RESULTS

Of 565 patients randomized, 443 patients (ertapenem = 219 and piperacillin/tazobactam = 224) were clinically evaluable for primary analysis. In the clinically evaluable population, the proportions of patients with favourable clinical response at DCIV were 93.6% (205/219) and 97.3% (218/224) in the ertapenem and piperacillin/tazobactam groups, respectively (difference: -3.8%, 95% CI: -8.3%, 0.0%). Ertapenem had a significantly lower favourable clinical response rate (91.5% versus 97.2%, 95% CI for difference: -12.1%, -0.3%) at DCIV in severe DFI patients. In the modified ITT population, 88.8% (237/267) and 90.6% (241/266) of patients in the ertapenem and piperacillin/tazobactam groups, respectively, had favourable clinical responses at DCIV (difference: -1.9%, 95% CI: -7.3%, 3.3%). Microbiological eradications of causative pathogens and adverse events were similar between treatment groups.

CONCLUSIONS

Treatment with ertapenem was non-inferior to piperacillin/tazobactam in Chinese patients with DFIs. Ertapenem treatment resulted in a markedly lower rate of clinical resolution in severe DFIs.

摘要

目的

在接受抗生素治疗的糖尿病足感染（DFI）中国患者中，比较抗生素方案的随机对照研究较少。我们评估了厄他培南与哌拉西林/他唑巴坦治疗中国 DFI 患者的疗效和安全性。

方法

需要接受静脉抗生素治疗的中重度 DFI 患者按 1:1 比例随机接受厄他培南（1.0 g 每日 1 次）或哌拉西林/他唑巴坦（4.5 g 每 8 小时）30 分钟静脉输注，至少 5 天。主要结局是静脉治疗停药时（DCIV）的临床疗效。对非劣效性评估人群在-15%处进行主要分析。评估安全性。ClinicalTrials.gov：NCT01370616。

结果

在 565 例随机患者中，443 例（厄他培南=219 例，哌拉西林/他唑巴坦=224 例）在临床可评估人群中进行了主要分析。在临床可评估人群中，厄他培南组和哌拉西林/他唑巴坦组 DCIV 时临床疗效良好的患者比例分别为 93.6%（205/219）和 97.3%（218/224）（差异：-3.8%，95%CI：-8.3%，0.0%）。在重度 DFI 患者中，厄他培南组的临床疗效良好率显著低于哌拉西林/他唑巴坦组（91.5%对 97.2%，95%CI 差值：-12.1%，-0.3%）。在改良意向治疗人群中，厄他培南组和哌拉西林/他唑巴坦组分别有 88.8%（237/267）和 90.6%（241/266）的患者 DCIV 时临床疗效良好（差异：-1.9%，95%CI：-7.3%，3.3%）。两组患者的病原体清除率和不良事件相似。