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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.
Furtado, Remo H M; Berwanger, Otavio; Fonseca, Henrique A; Corrêa, Thiago D; Ferraz, Leonardo R; Lapa, Maura G; Zampieri, Fernando G; Veiga, Viviane C; Azevedo, Luciano C P; Rosa, Regis G; Lopes, Renato D; Avezum, Alvaro; Manoel, Airton L O; Piza, Felipe M T; Martins, Priscilla A; Lisboa, Thiago C; Pereira, Adriano J; Olivato, Guilherme B; Dantas, Vicente C S; Milan, Eveline P; Gebara, Otavio C E; Amazonas, Roberto B; Oliveira, Monalisa B; Soares, Ronaldo V P; Moia, Diogo D F; Piano, Luciana P A; Castilho, Kleber; Momesso, Roberta G R A P; Schettino, Guilherme P P; Rizzo, Luiz Vicente; Neto, Ary Serpa; Machado, Flávia R; Cavalcanti, Alexandre B.
  • Furtado RHM; Hospital Israelita Albert Einstein, São Paulo, Brazil; Instituto do Coração, Hospital das Clinicas da Faculdade de Medicina, Universidade de São Paulo, Brazil.
  • Berwanger O; Hospital Israelita Albert Einstein, São Paulo, Brazil. Electronic address: otavio.berwanger@einstein.br.
  • Fonseca HA; Hospital Israelita Albert Einstein, São Paulo, Brazil.
  • Corrêa TD; Hospital Israelita Albert Einstein, São Paulo, Brazil; Brazilian Research in Intensive Care Network, São Paulo, Brazil.
  • Ferraz LR; Hospital Israelita Albert Einstein, São Paulo, Brazil.
  • Lapa MG; Hospital Israelita Albert Einstein, São Paulo, Brazil.
  • Zampieri FG; Brazilian Research in Intensive Care Network, São Paulo, Brazil; HCor Research Institute, São Paulo, Brazil.
  • Veiga VC; Brazilian Research in Intensive Care Network, São Paulo, Brazil; BP-A Beneficência Portuguesa de São Paulo, São Paulo, Brazil.
  • Azevedo LCP; Brazilian Research in Intensive Care Network, São Paulo, Brazil; Hospital Sírio Libanês Research and Education Institute, São Paulo, Brazil.
  • Rosa RG; Brazilian Research in Intensive Care Network, São Paulo, Brazil; Hospital Moinhos de Vento, Porto Alegre, Brazil.
  • Lopes RD; Brazilian Clinical Research Institute, São Paulo, Brazil; Duke University Medical Centre, Duke Clinical Research Institute, Durham, NC, USA.
  • Avezum A; International Research Center, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil.
  • Manoel ALO; Hospital Moyses Deustche (MBoi Mirim), São Paulo, Brazil.
  • Piza FMT; Hospital Moyses Deustche (MBoi Mirim), São Paulo, Brazil.
  • Martins PA; Hospital Estadual Jayme dos Santos Neves, Serra, Brazil.
  • Lisboa TC; Hospital de Clínicas, Porto Alegre, Brazil.
  • Pereira AJ; Hospital Israelita Albert Einstein, São Paulo, Brazil; Hospital Vila Santa Catarina, São Paulo, Brazil.
  • Olivato GB; Hospital Israelita Albert Einstein, São Paulo, Brazil; Hospital Vila Santa Catarina, São Paulo, Brazil.
  • Dantas VCS; Hospital Naval Marcílio Dias, Rio de Janeiro, Brazil.
  • Milan EP; Hospital Giselda Trigueiro, Natal, Brazil.
  • Gebara OCE; Hospital Santa Paula, São Paulo, Brazil.
  • Amazonas RB; EMS Pharma, Hortolândia, Brazil.
  • Oliveira MB; EMS Pharma, Hortolândia, Brazil.
  • Soares RVP; Hospital Israelita Albert Einstein, São Paulo, Brazil.
  • Moia DDF; Hospital Israelita Albert Einstein, São Paulo, Brazil.
  • Piano LPA; Hospital Israelita Albert Einstein, São Paulo, Brazil.
  • Castilho K; Hospital Israelita Albert Einstein, São Paulo, Brazil.
  • Momesso RGRAP; Hospital Israelita Albert Einstein, São Paulo, Brazil.
  • Schettino GPP; Hospital Israelita Albert Einstein, São Paulo, Brazil.
  • Rizzo LV; Hospital Israelita Albert Einstein, São Paulo, Brazil.
  • Neto AS; Hospital Israelita Albert Einstein, São Paulo, Brazil; Brazilian Research in Intensive Care Network, São Paulo, Brazil; Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
  • Machado FR; Brazilian Research in Intensive Care Network, São Paulo, Brazil; Department of Anesthesiology, Pain and Intensive Care Medicine, Universidade Federal de São Paulo, São Paulo, Brazil.
  • Cavalcanti AB; Brazilian Research in Intensive Care Network, São Paulo, Brazil; HCor Research Institute, São Paulo, Brazil.
Lancet ; 396(10256): 959-967, 2020 10 03.
Article in English | MEDLINE | ID: covidwho-748089
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 (11) 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.

FUNDING:

COALITION COVID-19 Brazil and EMS.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Pneumonia, Viral / Coronavirus Infections / Azithromycin / Hydroxychloroquine Type of study: Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Limits: Aged / Female / Humans / Male / Middle aged Country/Region as subject: South America / Brazil Language: English Journal: Lancet Year: 2020 Document Type: Article Affiliation country: S0140-6736(20)31862-6

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Pneumonia, Viral / Coronavirus Infections / Azithromycin / Hydroxychloroquine Type of study: Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Limits: Aged / Female / Humans / Male / Middle aged Country/Region as subject: South America / Brazil Language: English Journal: Lancet Year: 2020 Document Type: Article Affiliation country: S0140-6736(20)31862-6