Tags

Type your tag names separated by a space and hit enter

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.
Lancet. 2020 10 03; 396(10256):959-967.Lct

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.

FUNDING

COALITION COVID-19 Brazil and EMS.

Authors+Show Affiliations

Hospital Israelita Albert Einstein, São Paulo, Brazil; Instituto do Coração, Hospital das Clinicas da Faculdade de Medicina, Universidade de São Paulo, Brazil.Hospital Israelita Albert Einstein, São Paulo, Brazil. Electronic address: otavio.berwanger@einstein.br.Hospital Israelita Albert Einstein, São Paulo, Brazil.Hospital Israelita Albert Einstein, São Paulo, Brazil; Brazilian Research in Intensive Care Network, São Paulo, Brazil.Hospital Israelita Albert Einstein, São Paulo, Brazil.Hospital Israelita Albert Einstein, São Paulo, Brazil.Brazilian Research in Intensive Care Network, São Paulo, Brazil; HCor Research Institute, São Paulo, Brazil.Brazilian Research in Intensive Care Network, São Paulo, Brazil; BP-A Beneficência Portuguesa de São Paulo, São Paulo, Brazil.Brazilian Research in Intensive Care Network, São Paulo, Brazil; Hospital Sírio Libanês Research and Education Institute, São Paulo, Brazil.Brazilian Research in Intensive Care Network, São Paulo, Brazil; Hospital Moinhos de Vento, Porto Alegre, Brazil.Brazilian Clinical Research Institute, São Paulo, Brazil; Duke University Medical Centre, Duke Clinical Research Institute, Durham, NC, USA.International Research Center, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil.Hospital Moyses Deustche (MBoi Mirim), São Paulo, Brazil.Hospital Moyses Deustche (MBoi Mirim), São Paulo, Brazil.Hospital Estadual Jayme dos Santos Neves, Serra, Brazil.Hospital de Clínicas, Porto Alegre, Brazil.Hospital Israelita Albert Einstein, São Paulo, Brazil; Hospital Vila Santa Catarina, São Paulo, Brazil.Hospital Israelita Albert Einstein, São Paulo, Brazil; Hospital Vila Santa Catarina, São Paulo, Brazil.Hospital Naval Marcílio Dias, Rio de Janeiro, Brazil.Hospital Giselda Trigueiro, Natal, Brazil.Hospital Santa Paula, São Paulo, Brazil.EMS Pharma, Hortolândia, Brazil.EMS Pharma, Hortolândia, Brazil.Hospital Israelita Albert Einstein, São Paulo, Brazil.Hospital Israelita Albert Einstein, São Paulo, Brazil.Hospital Israelita Albert Einstein, São Paulo, Brazil.Hospital Israelita Albert Einstein, São Paulo, Brazil.Hospital Israelita Albert Einstein, São Paulo, Brazil.Hospital Israelita Albert Einstein, São Paulo, Brazil.Hospital Israelita Albert Einstein, São Paulo, Brazil.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.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.Brazilian Research in Intensive Care Network, São Paulo, Brazil; HCor Research Institute, São Paulo, Brazil.No affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32896292

Citation

Furtado, Remo H M., et al. "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." Lancet (London, England), vol. 396, no. 10256, 2020, pp. 959-967.
Furtado RHM, Berwanger O, Fonseca HA, et al. 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. Lancet. 2020;396(10256):959-967.
Furtado, R. H. M., Berwanger, O., Fonseca, H. A., Corrêa, T. D., Ferraz, L. R., Lapa, M. G., Zampieri, F. G., Veiga, V. C., Azevedo, L. C. P., Rosa, R. G., Lopes, R. D., Avezum, A., Manoel, A. L. O., Piza, F. M. T., Martins, P. A., Lisboa, T. C., Pereira, A. J., Olivato, G. B., Dantas, V. C. S., ... Cavalcanti, A. B. (2020). 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. Lancet (London, England), 396(10256), 959-967. https://doi.org/10.1016/S0140-6736(20)31862-6
Furtado RHM, et al. 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. Lancet. 2020 10 3;396(10256):959-967. PubMed PMID: 32896292.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Furtado,Remo H M, AU - Berwanger,Otavio, AU - Fonseca,Henrique A, AU - Corrêa,Thiago D, AU - Ferraz,Leonardo R, AU - Lapa,Maura G, AU - Zampieri,Fernando G, AU - Veiga,Viviane C, AU - Azevedo,Luciano C P, AU - Rosa,Regis G, AU - Lopes,Renato D, AU - Avezum,Alvaro, AU - Manoel,Airton L O, AU - Piza,Felipe M T, AU - Martins,Priscilla A, AU - Lisboa,Thiago C, AU - Pereira,Adriano J, AU - Olivato,Guilherme B, AU - Dantas,Vicente C S, AU - Milan,Eveline P, AU - Gebara,Otavio C E, AU - Amazonas,Roberto B, AU - Oliveira,Monalisa B, AU - Soares,Ronaldo V P, AU - Moia,Diogo D F, AU - Piano,Luciana P A, AU - Castilho,Kleber, AU - Momesso,Roberta G R A P, AU - Schettino,Guilherme P P, AU - Rizzo,Luiz Vicente, AU - Neto,Ary Serpa, AU - Machado,Flávia R, AU - Cavalcanti,Alexandre B, AU - ,, Y1 - 2020/09/05/ PY - 2020/07/07/received PY - 2020/08/11/revised PY - 2020/08/14/accepted PY - 2020/9/9/pubmed PY - 2020/9/9/medline PY - 2020/9/8/entrez SP - 959 EP - 967 JF - Lancet (London, England) JO - Lancet VL - 396 IS - 10256 N2 - 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. FUNDING: COALITION COVID-19 Brazil and EMS. SN - 1474-547X UR - https://www.unboundmedicine.com/medline/citation/32896292/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(20)31862-6 DB - PRIME DP - Unbound Medicine ER -