tetano
Editor, Senior Moderator
N Engl J Med
. 2020 Jul 23.
doi: 10.1056/NEJMoa2019014. Online ahead of print.
Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19
Alexandre B Cavalcanti[SUP] 1 [/SUP], Fernando G Zampieri[SUP] 1 [/SUP], Regis G Rosa[SUP] 1 [/SUP], Luciano C P Azevedo[SUP] 1 [/SUP], Viviane C Veiga[SUP] 1 [/SUP], Alvaro Avezum[SUP] 1 [/SUP], Lucas P Damiani[SUP] 1 [/SUP], Aline Marcadenti[SUP] 1 [/SUP], Let?cia Kawano-Dourado[SUP] 1 [/SUP], Thiago Lisboa[SUP] 1 [/SUP], Debora L M Junqueira[SUP] 1 [/SUP], Pedro G M de Barros E Silva[SUP] 1 [/SUP], Lucas Tramujas[SUP] 1 [/SUP], Erlon O Abreu-Silva[SUP] 1 [/SUP], Ligia N Laranjeira[SUP] 1 [/SUP], Aline T Soares[SUP] 1 [/SUP], Leandro S Echenique[SUP] 1 [/SUP], Adriano J Pereira[SUP] 1 [/SUP], Fl?vio G R Freitas[SUP] 1 [/SUP], Ot?vio C E Gebara[SUP] 1 [/SUP], Vicente C S Dantas[SUP] 1 [/SUP], Remo H M Furtado[SUP] 1 [/SUP], Eveline P Milan[SUP] 1 [/SUP], Nicole A Golin[SUP] 1 [/SUP], F?bio F Cardoso[SUP] 1 [/SUP], Israel S Maia[SUP] 1 [/SUP], Conrado R Hoffmann Filho[SUP] 1 [/SUP], Adrian P M Kormann[SUP] 1 [/SUP], Roberto B Amazonas[SUP] 1 [/SUP], Monalisa F Bocchi de Oliveira[SUP] 1 [/SUP], Ary Serpa-Neto[SUP] 1 [/SUP], Maicon Falavigna[SUP] 1 [/SUP], Renato D Lopes[SUP] 1 [/SUP], Fl?via R Machado[SUP] 1 [/SUP], Otavio Berwanger[SUP] 1 [/SUP], Coalition Covid-19 Brazil I Investigators
Affiliations
Abstract
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.).
. 2020 Jul 23.
doi: 10.1056/NEJMoa2019014. Online ahead of print.
Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19
Alexandre B Cavalcanti[SUP] 1 [/SUP], Fernando G Zampieri[SUP] 1 [/SUP], Regis G Rosa[SUP] 1 [/SUP], Luciano C P Azevedo[SUP] 1 [/SUP], Viviane C Veiga[SUP] 1 [/SUP], Alvaro Avezum[SUP] 1 [/SUP], Lucas P Damiani[SUP] 1 [/SUP], Aline Marcadenti[SUP] 1 [/SUP], Let?cia Kawano-Dourado[SUP] 1 [/SUP], Thiago Lisboa[SUP] 1 [/SUP], Debora L M Junqueira[SUP] 1 [/SUP], Pedro G M de Barros E Silva[SUP] 1 [/SUP], Lucas Tramujas[SUP] 1 [/SUP], Erlon O Abreu-Silva[SUP] 1 [/SUP], Ligia N Laranjeira[SUP] 1 [/SUP], Aline T Soares[SUP] 1 [/SUP], Leandro S Echenique[SUP] 1 [/SUP], Adriano J Pereira[SUP] 1 [/SUP], Fl?vio G R Freitas[SUP] 1 [/SUP], Ot?vio C E Gebara[SUP] 1 [/SUP], Vicente C S Dantas[SUP] 1 [/SUP], Remo H M Furtado[SUP] 1 [/SUP], Eveline P Milan[SUP] 1 [/SUP], Nicole A Golin[SUP] 1 [/SUP], F?bio F Cardoso[SUP] 1 [/SUP], Israel S Maia[SUP] 1 [/SUP], Conrado R Hoffmann Filho[SUP] 1 [/SUP], Adrian P M Kormann[SUP] 1 [/SUP], Roberto B Amazonas[SUP] 1 [/SUP], Monalisa F Bocchi de Oliveira[SUP] 1 [/SUP], Ary Serpa-Neto[SUP] 1 [/SUP], Maicon Falavigna[SUP] 1 [/SUP], Renato D Lopes[SUP] 1 [/SUP], Fl?via R Machado[SUP] 1 [/SUP], Otavio Berwanger[SUP] 1 [/SUP], Coalition Covid-19 Brazil I Investigators
Affiliations
- PMID: 32706953
- DOI: 10.1056/NEJMoa2019014
Abstract
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.).