巴西以色列阿尔伯特·爱因斯坦医院Otavio Berwanger团队研究了阿奇霉素联合标准方案治疗巴西重症COVID-19患者的效果。2020年9月4日，《柳叶刀》杂志发表了该成果。

阿奇霉素治疗COVID-19的有效性和安全性尚未明确。

研究组在巴西的57个中心进行了一项开放标签的随机临床试验，2020年3月28日至5月19日，共招募了447例疑似或确诊COVID-19且至少有一项附加严重程度标准的住院患者，即：补充氧流量大于4 L/min；使用高流量鼻腔插管；使用无创机械通气；或使用有创机械通气。将397例确诊患者随机分组，其中214例接受阿奇霉素联合标准治疗，183例仅接受标准治疗，巴西对重症COVID-19的标准治疗均包含羟氯喹治疗。

在改良意向治疗分析人群中，阿奇霉素组和对照组间患者的六点序贯量表评分无显著差异。两组间的不良事件发生率，包括临床相关室性心律失常、心脏骤停复苏、急性肾衰竭和校正QT间期延长等，均无统计学差异。

总之，阿奇霉素联合羟氯喹治疗重症COVID-19患者无益于改善临床结局。

附：英文原文

Title: Azithromycin in addition to standard of care versus standard of care alone in the treatment of patients admitted to the hospital with severe COVID-19 in Brazil (COALITION II): a randomised clinical trial

Author: Remo H M Furtado, Otavio Berwanger, Henrique A Fonseca, Thiago D Corrêa, Leonardo R Ferraz, Maura G Lapa, Fernando G Zampieri, Viviane C Veiga, Luciano C P Azevedo, Regis G Rosa, Renato D Lopes, Alvaro Avezum, Airton L O Manoel, Felipe M T Piza, Priscilla A Martins, Thiago C Lisboa, Adriano J Pereira, Guilherme B Olivato, Vicente C S Dantas, Eveline P Milan, Otavio C E Gebara, Roberto B Amazonas, Monalisa B Oliveira, Ronaldo V P Soares, Diogo D F Moia, Luciana P A Piano, Kleber Castilho, Roberta G R A P Momesso, Guilherme P P Schettino, Luiz Vicente Rizzo, Ary Serpa Neto, Flávia R Machado, Alexandre B Cavalcanti

Issue&Volume: 2020-09-04

Abstract:

Background

The efficacy and safety of azithromycin in the treatment of COVID-19 remain uncertain. We assessed whether adding azithromycin to standard of care, which included hydroxychloroquine, would improve clinical outcomes of patients admitted to the hospital with severe COVID-19.

Methods

We did an open-label, randomised clinical trial at 57 centres in Brazil. We enrolled patients admitted to hospital with suspected or confirmed COVID-19 and at least one additional severity criteria as follows: use of oxygen supplementation of more than 4 L/min flow; use of high-flow nasal cannula; use of non-invasive mechanical ventilation; or use of invasive mechanical ventilation. Patients were randomly assigned (1:1) to azithromycin (500 mg via oral, nasogastric, or intravenous administration once daily for 10 days) plus standard of care or to standard of care without macrolides. All patients received hydroxychloroquine (400 mg twice daily for 10 days) because that was part of standard of care treatment in Brazil for patients with severe COVID-19. The primary outcome, assessed by an independent adjudication committee masked to treatment allocation, was clinical status at day 15 after randomisation, assessed by a six-point ordinal scale, with levels ranging from 1 to 6 and higher scores indicating a worse condition (with odds ratio [OR] greater than 1·00 favouring the control group). The primary outcome was assessed in all patients in the intention-to-treat (ITT) population who had severe acute respiratory syndrome coronavirus 2 infection confirmed by molecular or serological testing before randomisation (ie, modified ITT [mITT] population). Safety was assessed in all patients according to which treatment they received, regardless of original group assignment. This trial was registered at ClinicalTrials.gov, NCT04321278.

Findings

447 patients were enrolled from March 28 to May 19, 2020. COVID-19 was confirmed in 397 patients who constituted the mITT population, of whom 214 were assigned to the azithromycin group and 183 to the control group. In the mITT population, the primary endpoint was not significantly different between the azithromycin and control groups (OR 1·36 [95% CI 0·94–1·97], p=0·11). Rates of adverse events, including clinically relevant ventricular arrhythmias, resuscitated cardiac arrest, acute kidney failure, and corrected QT interval prolongation, were not significantly different between groups.

Interpretation

In patients with severe COVID-19, adding azithromycin to standard of care treatment (which included hydroxychloroquine) did not improve clinical outcomes. Our findings do not support the routine use of azithromycin in combination with hydroxychloroquine in patients with severe COVID-19.

DOI: 10.1016/S0140-6736(20)31862-6

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31862-6/fulltext