国际原则试验协作组研究了在英国，阿奇霉素用于疑似COVID-19患者的社区治疗的效果。2021年3月4日，该研究发表在《柳叶刀》杂志上。
阿奇霉素是一种具有潜在抗病毒和抗炎特性的抗生素，已被用于治疗COVID-19，但缺乏来自社区随机试验的证据。
为了评估阿奇霉素治疗社区中并发症风险增加的疑似COVID-19患者的有效性，研究组在英国进行了一项初级保健、开放标签、多臂、适应性平台的针对COVID-19干预措施的随机试验，招募65岁及以上或50岁及以上至少有一种共病的人群，将其随机分组，疑似COVID-19患者身体不适在两周以内，每日服用阿奇霉素+常规治疗，或其他干预措施，或仅接受常规治疗。随机分组后28天内评估两个主要终点：第一次自我报告恢复的时间；与COVID-19相关的住院或死亡。
2020年5月22日至11月30日，研究组共招募了2265名参与者，其中540名接受阿奇霉素加常规治疗，875名接受单独常规治疗，850名接受其他干预措施。2265名参与者中有2120名（94%）提供了随访数据并被纳入贝叶斯初级分析，其中阿奇霉素联合常规治疗组中有500名，单独常规治疗组中有823名，其他干预组中有797名参与者。
阿奇霉素联合常规治疗组中有402人（80%）在28天内感觉恢复，单纯常规治疗组中有631人（77%）。阿奇霉素联合常规治疗组在首次报告的恢复时间与单独常规治疗组相比，未显示有明显获益，风险比为1.08。有临床意义的恢复时间获益至少1.5天的的概率为0.23。
阿奇霉素联合常规治疗组中有16名（3%）患者住院治疗，单纯常规治疗组中有28名（3%）。两个研究组均无死亡病例。两组的安全性结果相似。阿奇霉素加常规治疗组参与者中有2名（1%）在试验期间报告与COVID-19无关的入院，单独常规治疗组参与者中有4名（1%）。
研究结果不能证明常规使用阿奇霉素可以减少社区疑似COVID-19患者的康复时间或住院风险。
附：英文原文
Title: Azithromycin for community treatment of suspected COVID-19 in people at increased risk of an adverse clinical course in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial
Author: Christopher C Butler, Jienchi Dorward, Ly-Mee Yu, Oghenekome Gbinigie, Gail Hayward, Benjamin R Saville, Oliver Van Hecke, Nick Berry, Michelle Detry, Christina Saunders, Mark Fitzgerald, Victoria Harris, Mahendra G Patel, Simon de Lusignan, Emma Ogburn, Philip H Evans, Nicholas PB Thomas, FD Richard Hobbs
Issue&Volume: 2021-03-04
Abstract:
Background
Azithromycin, an antibiotic with potential antiviral and anti-inflammatory properties, has been used to treat COVID-19, but evidence from community randomised trials is lacking. We aimed to assess the effectiveness of azithromycin to treat suspected COVID-19 among people in the community who had an increased risk of complications.
Methods
In this UK-based, primary care, open-label, multi-arm, adaptive platform randomised trial of interventions against COVID-19 in people at increased risk of an adverse clinical course (PRINCIPLE), we randomly assigned people aged 65 years and older, or 50 years and older with at least one comorbidity, who had been unwell for 14 days or less with suspected COVID-19, to usual care plus azithromycin 500 mg daily for three days, usual care plus other interventions, or usual care alone. The trial had two coprimary endpoints measured within 28 days from randomisation: time to first self-reported recovery, analysed using a Bayesian piecewise exponential, and hospital admission or death related to COVID-19, analysed using a Bayesian logistic regression model. Eligible participants with outcome data were included in the primary analysis, and those who received the allocated treatment were included in the safety analysis. The trial is registered with ISRCTN, ISRCTN86534580.
Findings
The first participant was recruited to PRINCIPLE on April 2, 2020. The azithromycin group enrolled participants between May 22 and Nov 30, 2020, by which time 2265 participants had been randomly assigned, 540 to azithromycin plus usual care, 875 to usual care alone, and 850 to other interventions. 2120 (94%) of 2265 participants provided follow-up data and were included in the Bayesian primary analysis, 500 participants in the azithromycin plus usual care group, 823 in the usual care alone group, and 797 in other intervention groups. 402 (80%) of 500 participants in the azithromycin plus usual care group and 631 (77%) of 823 participants in the usual care alone group reported feeling recovered within 28 days. We found little evidence of a meaningful benefit in the azithromycin plus usual care group in time to first reported recovery versus usual care alone (hazard ratio 1·08, 95% Bayesian credibility interval [BCI] 0·95 to 1·23), equating to an estimated benefit in median time to first recovery of 0·94 days (95% BCI 0·56 to 2·43). The probability that there was a clinically meaningful benefit of at least 1·5 days in time to recovery was 0·23. 16 (3%) of 500 participants in the azithromycin plus usual care group and 28 (3%) of 823 participants in the usual care alone group were hospitalised (absolute benefit in percentage 0·3%, 95% BCI 1·7 to 2·2). There were no deaths in either study group. Safety outcomes were similar in both groups. Two (1%) of 455 participants in the azothromycin plus usual care group and four (1%) of 668 participants in the usual care alone group reported admission to hospital during the trial, not related to COVID-19.
Interpretation
Our findings do not justify the routine use of azithromycin for reducing time to recovery or risk of hospitalisation for people with suspected COVID-19 in the community. These findings have important antibiotic stewardship implications during this pandemic, as inappropriate use of antibiotics leads to increased antimicrobial resistance, and there is evidence that azithromycin use increased during the pandemic in the UK.
DOI: 10.1016/S0140-6736(21)00461-X
Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00461-X/fulltext
LANCET：《柳叶刀》，创刊于1823年。隶属于爱思唯尔出版社，最新IF：202.731
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