 本/期/解/读 阿奇霉素对需要住院治疗的AECOPD患者的疗效（BACE）分析：一项多中心、随机、双盲、安慰剂对照试验 Azithromycin during Acute COPD Exacerbations Requiring Hospitalization (BACE): a Multicentre, Randomized, Double‐blind, Placebo‐controlled Trial 关键词 大环内脂类，复合物，事件时间，治疗失败，再入院 作者： Kristina Vermeersch, et al. 翻译： 北京协和医院呼吸内科 孙宇新 黄 慧 文献来源： AJRCCM. 2019 May 3. DOI: 10.1164/rccm.201901-0094OC  背景及目的 阿奇霉素可预防COPD患者发生急性加重（AECOPD），但其对需住院治疗的AECOPD患者的疗效尚不明确。本研究在患者初入院时即在标准治疗基础上加用小剂量的阿奇霉素3月，来探究阿奇霉素是否可减少AECOPD治疗失败（TF）的发生。 方 法 本研究是研究者发起的，多中心、随机、双盲、安慰剂对照试验中，纳入吸烟≥10包年且前一年急性加重次数≥1次的AECOPD住院患者，在入院后48小时内被随机（1:1）分为阿奇霉素组或安慰剂组。在全身激素联合抗生素的AECOPD标准治疗基础上加用研究药物（负荷剂量500mg/d×3d，维持剂量250mg Qod×3m）。随访6个月，主要终点是3月内TF事件的发生率（TF-治疗失败是指：因COPD需全身激素和/或抗生素加强化治疗(TI)、需升级治疗级别、需再入院治疗（SH），以及全因死亡率。 结 果 共筛选出301例患者，随机分为阿奇霉素组(147例)和安慰剂组(154例)。3个月内阿奇霉素组TF率为49%，安慰剂组TF率为60% 【HR=0.73；95%CI为（0.53-1.01）；p=0.0526】。比较3个月内阿奇霉素组与安慰剂组的TI率、SH率和死亡率分别为47% vs 60%(p=0.0272)、13% vs 28%(p=0.0024)和2% vs 4%(p=0.5075)。停药6月后阿奇霉素相关的该疗效不复存在。 结 论 对于需住院治疗的感染性AECOPD患者，连续3月的低剂量阿奇霉素维持治疗可显著降低AECOPD高危期TF的发生；且为维持该疗效，建议适当延长阿奇霉素使用时间。 原文摘要 Rationale Azithromycin prevents acute exacerbations in COPD (AECOPD); however, its value in the treatment of AECOPD requiring hospitalization is yet to be defined. Objective We investigated whether a 3-month intervention with low-dose azithromycin could decrease treatment failure (TF) when initiated at hospital admission and added to standard care. Methods In an investigator-initiated, multi-centre, randomized, double·blind, placebo-controlled trial, patients hospitalized for an AECOPD, with a smoking history of ≥ 10 pack-years and ≥ 1 exacerbation in the previous year, were randomized (1:1) within 48-hours of admission to azithromycin or placebo. The study drug (500mg/day for 3 days) was administered on top of a standardized acute treatment of systemic corticosteroids and antibiotics, and subsequently continued for 3 months (3m) (250mg/2days). Patients were followed-up for 6m thereafter. Time-to-first event analyses evaluated the TF rate within 3m as a novel primary endpoint in the intention-to-treat population, with TF defined as the composite of treatment intensification with systemic corticosteroids and/or antibiotics (TI), step-up in hospital care or readmission for respiratory reasons (SH) or all‐cause mortality. Main results 301 patients were randomized to azithromycin (n=147) or placebo (n=154). The TF rate within 3m was 49% in the azithromycin and 60% in the placebo group (HR=0.73; 95%CI 0.53-1.01; p=0.0526). TI, SH and mortality rates within 3m were 47% vs 60% (p=0.0272), 13% vs 28% (p=0.0024) and 2% vs 4% (p=0.5075), respectively. Clinical benefits were lost 6m after withdrawal. Conclusions 3m of azithromycin for infectious AECOPD requiring hospitalization may significantly reduce TF during the highest risk period. Prolonged treatment seems needed to maintain clinical benefits.  文字来源：孙宇新 黄 慧 |
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