Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19.

Journal Article (Journal Article;Multicenter Study)

BACKGROUND: Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is limited. METHODS: We conducted a multicenter, randomized, open-label, three-group, controlled trial involving hospitalized patients with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a maximum of 4 liters per minute of supplemental oxygen. Patients were randomly assigned in a 1:1:1 ratio to receive standard care, standard care plus hydroxychloroquine at a dose of 400 mg twice daily, or standard care plus hydroxychloroquine at a dose of 400 mg twice daily plus azithromycin at a dose of 500 mg once daily for 7 days. The primary outcome was clinical status at 15 days as assessed with the use of a seven-level ordinal scale (with levels ranging from one to seven and higher scores indicating a worse condition) in the modified intention-to-treat population (patients with a confirmed diagnosis of Covid-19). Safety was also assessed. RESULTS: A total of 667 patients underwent randomization; 504 patients had confirmed Covid-19 and were included in the modified intention-to-treat analysis. As compared with standard care, the proportional odds of having a higher score on the seven-point ordinal scale at 15 days was not affected by either hydroxychloroquine alone (odds ratio, 1.21; 95% confidence interval [CI], 0.69 to 2.11; P = 1.00) or hydroxychloroquine plus azithromycin (odds ratio, 0.99; 95% CI, 0.57 to 1.73; P = 1.00). Prolongation of the corrected QT interval and elevation of liver-enzyme levels were more frequent in patients receiving hydroxychloroquine, alone or with azithromycin, than in those who were not receiving either agent. CONCLUSIONS: Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care. (Funded by the Coalition Covid-19 Brazil and EMS Pharma; ClinicalTrials.gov number, NCT04322123.).

Full Text

Duke Authors

Cited Authors

  • Cavalcanti, AB; Zampieri, FG; Rosa, RG; Azevedo, LCP; Veiga, VC; Avezum, A; Damiani, LP; Marcadenti, A; Kawano-Dourado, L; Lisboa, T; Junqueira, DLM; de Barros E Silva, PGM; Tramujas, L; Abreu-Silva, EO; Laranjeira, LN; Soares, AT; Echenique, LS; Pereira, AJ; Freitas, FGR; Gebara, OCE; Dantas, VCS; Furtado, RHM; Milan, EP; Golin, NA; Cardoso, FF; Maia, IS; Hoffmann Filho, CR; Kormann, APM; Amazonas, RB; Bocchi de Oliveira, MF; Serpa-Neto, A; Falavigna, M; Lopes, RD; Machado, FR; Berwanger, O; Coalition Covid-19 Brazil I Investigators,

Published Date

  • November 19, 2020

Published In

Volume / Issue

  • 383 / 21

Start / End Page

  • 2041 - 2052

PubMed ID

  • 32706953

Pubmed Central ID

  • PMC7397242

Electronic International Standard Serial Number (EISSN)

  • 1533-4406

Digital Object Identifier (DOI)

  • 10.1056/NEJMoa2019014


  • eng

Conference Location

  • United States