Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19
Copyright © 2020 Massachusetts Medical Society..
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.).
| Errataetall: |
ErratumIn: N Engl J Med. 2020 Nov 19;383(21):e119. - PMID 33210858 |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:383 |
|---|---|
| Enthalten in: |
The New England journal of medicine - 383(2020), 21 vom: 19. Nov., Seite 2041-2052 |
| Sprache: |
Englisch |
|---|
| Links: |
|---|
| Themen: |
4QWG6N8QKH |
|---|
| Anmerkungen: |
Date Completed 01.12.2020 Date Revised 23.11.2023 published: Print-Electronic ClinicalTrials.gov: NCT04322123 ErratumIn: N Engl J Med. 2020 Nov 19;383(21):e119. - PMID 33210858 Citation Status MEDLINE |
|---|
| doi: |
10.1056/NEJMoa2019014 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM312829329 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM312829329 | ||
| 003 | DE-627 | ||
| 005 | 20231225145243.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1056/NEJMoa2019014 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1042.xml |
| 035 | |a (DE-627)NLM312829329 | ||
| 035 | |a (NLM)32706953 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Cavalcanti, Alexandre B |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19 |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 01.12.2020 | ||
| 500 | |a Date Revised 23.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT04322123 | ||
| 500 | |a ErratumIn: N Engl J Med. 2020 Nov 19;383(21):e119. - PMID 33210858 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 Massachusetts Medical Society. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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.) | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 650 | 7 | |a Hydroxychloroquine |2 NLM | |
| 650 | 7 | |a 4QWG6N8QKH |2 NLM | |
| 650 | 7 | |a Azithromycin |2 NLM | |
| 650 | 7 | |a 83905-01-5 |2 NLM | |
| 700 | 1 | |a Zampieri, Fernando G |e verfasserin |4 aut | |
| 700 | 1 | |a Rosa, Regis G |e verfasserin |4 aut | |
| 700 | 1 | |a Azevedo, Luciano C P |e verfasserin |4 aut | |
| 700 | 1 | |a Veiga, Viviane C |e verfasserin |4 aut | |
| 700 | 1 | |a Avezum, Alvaro |e verfasserin |4 aut | |
| 700 | 1 | |a Damiani, Lucas P |e verfasserin |4 aut | |
| 700 | 1 | |a Marcadenti, Aline |e verfasserin |4 aut | |
| 700 | 1 | |a Kawano-Dourado, Letícia |e verfasserin |4 aut | |
| 700 | 1 | |a Lisboa, Thiago |e verfasserin |4 aut | |
| 700 | 1 | |a Junqueira, Debora L M |e verfasserin |4 aut | |
| 700 | 1 | |a de Barros E Silva, Pedro G M |e verfasserin |4 aut | |
| 700 | 1 | |a Tramujas, Lucas |e verfasserin |4 aut | |
| 700 | 1 | |a Abreu-Silva, Erlon O |e verfasserin |4 aut | |
| 700 | 1 | |a Laranjeira, Ligia N |e verfasserin |4 aut | |
| 700 | 1 | |a Soares, Aline T |e verfasserin |4 aut | |
| 700 | 1 | |a Echenique, Leandro S |e verfasserin |4 aut | |
| 700 | 1 | |a Pereira, Adriano J |e verfasserin |4 aut | |
| 700 | 1 | |a Freitas, Flávio G R |e verfasserin |4 aut | |
| 700 | 1 | |a Gebara, Otávio C E |e verfasserin |4 aut | |
| 700 | 1 | |a Dantas, Vicente C S |e verfasserin |4 aut | |
| 700 | 1 | |a Furtado, Remo H M |e verfasserin |4 aut | |
| 700 | 1 | |a Milan, Eveline P |e verfasserin |4 aut | |
| 700 | 1 | |a Golin, Nicole A |e verfasserin |4 aut | |
| 700 | 1 | |a Cardoso, Fábio F |e verfasserin |4 aut | |
| 700 | 1 | |a Maia, Israel S |e verfasserin |4 aut | |
| 700 | 1 | |a Hoffmann Filho, Conrado R |e verfasserin |4 aut | |
| 700 | 1 | |a Kormann, Adrian P M |e verfasserin |4 aut | |
| 700 | 1 | |a Amazonas, Roberto B |e verfasserin |4 aut | |
| 700 | 1 | |a Bocchi de Oliveira, Monalisa F |e verfasserin |4 aut | |
| 700 | 1 | |a Serpa-Neto, Ary |e verfasserin |4 aut | |
| 700 | 1 | |a Falavigna, Maicon |e verfasserin |4 aut | |
| 700 | 1 | |a Lopes, Renato D |e verfasserin |4 aut | |
| 700 | 1 | |a Machado, Flávia R |e verfasserin |4 aut | |
| 700 | 1 | |a Berwanger, Otavio |e verfasserin |4 aut | |
| 700 | 0 | |a Coalition Covid-19 Brazil I Investigators |e verfasserin |4 aut | |
| 700 | 1 | |a Cavalcanti, Alexandre B |e investigator |4 oth | |
| 700 | 1 | |a Rosa, Regis |e investigator |4 oth | |
| 700 | 1 | |a Azevedo, Luciano C P |e investigator |4 oth | |
| 700 | 1 | |a Avezum, Alvaro |e investigator |4 oth | |
| 700 | 1 | |a Veiga, Viviane C |e investigator |4 oth | |
| 700 | 1 | |a Lopes, Renato D |e investigator |4 oth | |
| 700 | 1 | |a Machado, Flávia R |e investigator |4 oth | |
| 700 | 1 | |a Berwanger, Otavio |e investigator |4 oth | |
| 700 | 1 | |a Zampieri, Fernando G |e investigator |4 oth | |
| 700 | 1 | |a Kawano-Dourado, Letícia |e investigator |4 oth | |
| 700 | 1 | |a Lisboa, Thiago |e investigator |4 oth | |
| 700 | 1 | |a Maia, Israel S |e investigator |4 oth | |
| 700 | 1 | |a Furtado, Remo |e investigator |4 oth | |
| 700 | 1 | |a Fonseca, Henrique |e investigator |4 oth | |
| 700 | 1 | |a Serpa-Neto, Ary |e investigator |4 oth | |
| 700 | 1 | |a Correa, Thiago |e investigator |4 oth | |
| 700 | 1 | |a Galvão, Cláudio |e investigator |4 oth | |
| 700 | 1 | |a Ferraz, Leonardo R |e investigator |4 oth | |
| 700 | 1 | |a Schettino, Guilherme |e investigator |4 oth | |
| 700 | 1 | |a Rizzo, Luiz V |e investigator |4 oth | |
| 700 | 1 | |a Falavigna, Maicon |e investigator |4 oth | |
| 700 | 1 | |a Leite, Eduardo |e investigator |4 oth | |
| 700 | 1 | |a Tomazini, Bruno M |e investigator |4 oth | |
| 700 | 1 | |a Leão, Danielle |e investigator |4 oth | |
| 700 | 1 | |a Prats, João |e investigator |4 oth | |
| 700 | 1 | |a Scheinberg, Philip |e investigator |4 oth | |
| 700 | 1 | |a Gobatto, André |e investigator |4 oth | |
| 700 | 1 | |a Grion, Cintia |e investigator |4 oth | |
| 700 | 1 | |a Dal Pizzol, Felipe |e investigator |4 oth | |
| 700 | 1 | |a Bozza, Fernando A |e investigator |4 oth | |
| 700 | 1 | |a Freitas, Flavio G R |e investigator |4 oth | |
| 700 | 1 | |a Westphal, Glauco |e investigator |4 oth | |
| 700 | 1 | |a Urbano, Hugo |e investigator |4 oth | |
| 700 | 1 | |a Biondi, Rodrigo |e investigator |4 oth | |
| 700 | 1 | |a Figueiredo, Rodrigo C |e investigator |4 oth | |
| 700 | 1 | |a Laranjeira, Ligia N |e investigator |4 oth | |
| 700 | 1 | |a Paisani, Denise |e investigator |4 oth | |
| 700 | 1 | |a Damiani, Lucas P |e investigator |4 oth | |
| 700 | 1 | |a Valeis, Nanci |e investigator |4 oth | |
| 700 | 1 | |a Abait, Tamiris |e investigator |4 oth | |
| 700 | 1 | |a Negrelli, Karina |e investigator |4 oth | |
| 700 | 1 | |a Santucci, Eliana V |e investigator |4 oth | |
| 700 | 1 | |a Silva, Jacqueline T |e investigator |4 oth | |
| 700 | 1 | |a Machado, Rachel H V |e investigator |4 oth | |
| 700 | 1 | |a Ferreira, Angela C B |e investigator |4 oth | |
| 700 | 1 | |a Torreglosa, Camila R |e investigator |4 oth | |
| 700 | 1 | |a de Souza, Alline S |e investigator |4 oth | |
| 700 | 1 | |a Albuquerque, Aline |e investigator |4 oth | |
| 700 | 1 | |a Vianna, Bruna M P |e investigator |4 oth | |
| 700 | 1 | |a Kojima, Flavia C S |e investigator |4 oth | |
| 700 | 1 | |a Batista, Gabriela V |e investigator |4 oth | |
| 700 | 1 | |a Soares, Rafael M |e investigator |4 oth | |
| 700 | 1 | |a Homsi, Jordana R |e investigator |4 oth | |
| 700 | 1 | |a Campos, Viviane B |e investigator |4 oth | |
| 700 | 1 | |a Torres Bueno, Priscila Regina |e investigator |4 oth | |
| 700 | 1 | |a Pinheiro do Carmo Gomes, Samara |e investigator |4 oth | |
| 700 | 1 | |a de Andrade Jesuino, Isabella |e investigator |4 oth | |
| 700 | 1 | |a de Souza, Denise |e investigator |4 oth | |
| 700 | 1 | |a Sanchez, Evelin C |e investigator |4 oth | |
| 700 | 1 | |a de Oliveira, Débora M |e investigator |4 oth | |
| 700 | 1 | |a Trott, Geraldine |e investigator |4 oth | |
| 700 | 1 | |a Gimenes, Bruna P |e investigator |4 oth | |
| 700 | 1 | |a da Silva, Sabrina S |e investigator |4 oth | |
| 700 | 1 | |a Dos Santos, Rosa R M |e investigator |4 oth | |
| 700 | 1 | |a Amazonas, Roberto B |e investigator |4 oth | |
| 700 | 1 | |a Bocchi de Oliveira, Monalisa F |e investigator |4 oth | |
| 700 | 1 | |a Suarez, José A O |e investigator |4 oth | |
| 700 | 1 | |a Peleias, Andrei G |e investigator |4 oth | |
| 700 | 1 | |a Elias do Valle, Arcangela C |e investigator |4 oth | |
| 700 | 1 | |a Kummer, Arthur M E |e investigator |4 oth | |
| 700 | 1 | |a Bellomo, Rinaldo |e investigator |4 oth | |
| 700 | 1 | |a Bailey, Michael |e investigator |4 oth | |
| 700 | 1 | |a Young, Paul |e investigator |4 oth | |
| 700 | 1 | |a Pereira, Adriano José |e investigator |4 oth | |
| 700 | 1 | |a Barriviera de Torre, Jimena Eva |e investigator |4 oth | |
| 700 | 1 | |a de Castro Jorge Racy, Fábio |e investigator |4 oth | |
| 700 | 1 | |a da Silva, Vinicius Ponzio |e investigator |4 oth | |
| 700 | 1 | |a Codeço, Artur Martins |e investigator |4 oth | |
| 700 | 1 | |a Eluf Gebara, Otavio Celso |e investigator |4 oth | |
| 700 | 1 | |a Sacci de Freitas Santos, Rodrigo |e investigator |4 oth | |
| 700 | 1 | |a Borges, Fabricio Assami |e investigator |4 oth | |
| 700 | 1 | |a Alvares Lopes, Ana Tarina |e investigator |4 oth | |
| 700 | 1 | |a Cordeiro Dos Santos, Gabriel Augusto |e investigator |4 oth | |
| 700 | 1 | |a Furtado, Remo Holanda |e investigator |4 oth | |
| 700 | 1 | |a Serpa Neto, Ary |e investigator |4 oth | |
| 700 | 1 | |a Cardoso, Fábio Fernandes |e investigator |4 oth | |
| 700 | 1 | |a Ribeiro de Campos, Mônica |e investigator |4 oth | |
| 700 | 1 | |a Pereira Mallman, Lucas |e investigator |4 oth | |
| 700 | 1 | |a Dos Santos Costa, Cristiane |e investigator |4 oth | |
| 700 | 1 | |a Hoffmann Filho, Conrado Roberto |e investigator |4 oth | |
| 700 | 1 | |a Squizato Alano, Joaquim |e investigator |4 oth | |
| 700 | 1 | |a Avanzi, Natalia |e investigator |4 oth | |
| 700 | 1 | |a de Souza Junior, Gedealvares Francisco |e investigator |4 oth | |
| 700 | 1 | |a Vicente da Penha, Renata |e investigator |4 oth | |
| 700 | 1 | |a de Aquino Martins, Priscilla |e investigator |4 oth | |
| 700 | 1 | |a D'Oliveira Vieira, Ricardo |e investigator |4 oth | |
| 700 | 1 | |a Vicente da Silva, Daniel |e investigator |4 oth | |
| 700 | 1 | |a Carvalho Grion, Cintia Magalhães |e investigator |4 oth | |
| 700 | 1 | |a Pipolo Milan, Eveline |e investigator |4 oth | |
| 700 | 1 | |a Baumgardt Bay, Monica |e investigator |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |t The New England journal of medicine |d 1945 |g 383(2020), 21 vom: 19. Nov., Seite 2041-2052 |w (DE-627)NLM000008184 |x 1533-4406 |7 nnns |
| 773 | 1 | 8 | |g volume:383 |g year:2020 |g number:21 |g day:19 |g month:11 |g pages:2041-2052 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1056/NEJMoa2019014 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 383 |j 2020 |e 21 |b 19 |c 11 |h 2041-2052 | ||