3天口服纳红霉素与口服莫西沙星治疗成人社区获得性细菌性肺炎的疗效和安全性比较：一项III期随机双盲对照试验

IF 6.2 Q1 HEALTH CARE SCIENCES & SERVICES

The Lancet regional health. Southeast Asia Pub Date : 2025-09-23 DOI:10.1016/j.lansea.2025.100666

Himanshu Pophale , Monica Gupta , Lily Llorens , Piotr Iwanowski , Ranjeet Gutte , Rajesh Chavan , Anasuya Patel , Harsha Agrawal , Snehal Palwe , Prashant Joshi , Hariharan Periasamy , Mahesh Patel , Balaji Veeraraghavan , Sachin Bhagwat

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引用次数: 0

摘要

nafithromycin是一种新型的大环内酯类内酯类药物，在体外对引起社区获得性细菌性肺炎（CABP）的病原体表现出优异的效力，同时具有高且持续的肺浓度，允许每日一次给药。我们的目的是比较那霉素与莫西沙星治疗CABP的疗效和安全性。方法：这是一项III期、随机、双盲、非劣效性研究，在印度31个地点进行了成人CABP （PORT风险等级为II、III、IV）。采用交互式语音/网络应答系统进行分组随机（1:1）随机化，分别给予口服纳霉素800 mg q24h，连续3天或口服莫西沙星400 mg q24h，连续7天。主要疗效终点是在修改意向治疗人群（MITT）中第4天出现早期临床反应（ECR）的患者比例。良好ECR定义为与基线相比，存活且≥2个CABP症状改善≥1个水平，且没有其他CABP症状恶化。采用了12.5%的非劣效性裕度。该试验已在印度临床试验注册中心注册（CTRI/2019/11/021964）。在2021年2月至2023年6月期间，共有488名患者入组，其中244名随机分为两组。MITT人群包括477例患者，其中40%属于PORT风险III/IV级。组间人口统计学和基线特征具有可比性。非红霉素组和莫西沙星组分别有91.3%（220/241）和89.0%（210/236）的患者出现ECR[差异，2.3%；95% CI(−3.1,7.8)]建立了治疗间的统计学非劣效性。最常见的治疗不良事件报告（≥2%的患者在任何治疗组）是腹痛，腹泻，头痛和恶心，其严重程度均为轻度。结论口服纳霉素3天治疗CABP的效果不低于口服莫西沙星7天治疗CABP的效果。由Wockhardt和印度政府生物技术部BIRAC共同资助。

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Efficacy and safety of a 3-day once-daily regimen of oral nafithromycin in comparison to oral moxifloxacin for the treatment of community-acquired bacterial pneumonia in adults: a phase III, randomized, double-blind controlled trial

Background

Nafithromycin, a novel macrolide belonging to the lactone ketolide subclass, exhibits excellent in vitro potency against pathogens causing community-acquired bacterial pneumonia (CABP), in conjunction with high and sustained pulmonary concentrations allowing for once-daily dosing. We aimed to compare efficacy and safety of nafithromycin with moxifloxacin for treatment of CABP.

Methods

This was a phase III, randomized, double-blind, non-inferiority study in adults with CABP (PORT risk class II, III, IV), conducted at 31 sites across India. Patients were randomized (1:1) via block randomisation using interactive voice/web response system to receive oral nafithromycin 800 mg q24h for 3 days or oral moxifloxacin 400 mg q24h for 7 days. The primary efficacy endpoint was the proportion of patients with early clinical response (ECR) at Day 4 in the modified-intent-to-treat population (MITT). Favourable ECR was defined as alive and ≥1 level improvement in ≥2 CABP symptoms compared to baseline and without worsening of other CABP symptoms. A non-inferiority margin of 12.5% was utilised. This trial is registered with Clinical Trial Registry—India (CTRI/2019/11/021964).

Findings

Between February 2021 and June 2023, 488 patients were enrolled with 244 randomized to each treatment. MITT population included 477 patients with 40% belonging to PORT risk class III/IV. Demography and baseline characteristics were comparable between groups. ECR was observed in 91.3% (220/241) of patients in nafithromycin group and 89.0% (210/236) of patients in moxifloxacin group of the MITT population [difference, 2.3%; 95% CI (−3.1, 7.8)] establishing statistical non-inferiority between treatments. Most common treatment-emergent adverse events reported (≥2% patients in any treatment group) were abdominal pain, diarrhoea, headache and nausea, which were all mild in severity.