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Hydroxychloroquine versus placebo in the treatment of non-hospitalised patients with COVID-19 (COPE – Coalition V): A double-blind, multicentre, randomised, controlled trial

BACKGROUND: Previous Randomised controlled trials (RCT) evaluating chloroquine and hydroxychloroquine in non-hospitalised COVID-19 patients have found no significant difference in hospitalisation rates. However, low statistical power precluded definitive answers. METHODS: We conducted a multicenter,...

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Autores principales: Avezum, Álvaro, Oliveira, Gustavo B F, Oliveira, Haliton, Lucchetta, Rosa C, Pereira, Valéria F A, Dabarian, André L, D´O Vieira, Ricardo, Silva, Daniel V, Kormann, Adrian P M, Tognon, Alexandre P, De Gasperi, Ricardo, Hernandes, Mauro E, Feitosa, Audes D M, Piscopo, Agnaldo, Souza, André S, Miguel, Carlos H, Nogueira, Vinicius O, Minelli, César, Magalhães, Carlos C, Morejon, Karen M L, Bicudo, Letícia S, Souza, Germano E C, Gomes, Marco A M, Fo, José J F Raposo, Schwarzbold, Alexandre V, Zilli, Alexandre, Amazonas, Roberto B, Moreira, Frederico R, Alves, Lucas B O, Assis, Silvia R L, Neves, Precil D M M, Matuoka, Jessica Y, Boszczowski, Icaro, Catarino, Daniela G M, Veiga, Viviane C, Azevedo, Luciano C P, Rosa, Regis G, Lopes, Renato D, Cavalcanti, Alexandre B, Berwanger, Otavio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968238/
https://www.ncbi.nlm.nih.gov/pubmed/35378952
http://dx.doi.org/10.1016/j.lana.2022.100243
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author Avezum, Álvaro
Oliveira, Gustavo B F
Oliveira, Haliton
Lucchetta, Rosa C
Pereira, Valéria F A
Dabarian, André L
D´O Vieira, Ricardo
Silva, Daniel V
Kormann, Adrian P M
Tognon, Alexandre P
De Gasperi, Ricardo
Hernandes, Mauro E
Feitosa, Audes D M
Piscopo, Agnaldo
Souza, André S
Miguel, Carlos H
Nogueira, Vinicius O
Minelli, César
Magalhães, Carlos C
Morejon, Karen M L
Bicudo, Letícia S
Souza, Germano E C
Gomes, Marco A M
Fo, José J F Raposo
Schwarzbold, Alexandre V
Zilli, Alexandre
Amazonas, Roberto B
Moreira, Frederico R
Alves, Lucas B O
Assis, Silvia R L
Neves, Precil D M M
Matuoka, Jessica Y
Boszczowski, Icaro
Catarino, Daniela G M
Veiga, Viviane C
Azevedo, Luciano C P
Rosa, Regis G
Lopes, Renato D
Cavalcanti, Alexandre B
Berwanger, Otavio
author_facet Avezum, Álvaro
Oliveira, Gustavo B F
Oliveira, Haliton
Lucchetta, Rosa C
Pereira, Valéria F A
Dabarian, André L
D´O Vieira, Ricardo
Silva, Daniel V
Kormann, Adrian P M
Tognon, Alexandre P
De Gasperi, Ricardo
Hernandes, Mauro E
Feitosa, Audes D M
Piscopo, Agnaldo
Souza, André S
Miguel, Carlos H
Nogueira, Vinicius O
Minelli, César
Magalhães, Carlos C
Morejon, Karen M L
Bicudo, Letícia S
Souza, Germano E C
Gomes, Marco A M
Fo, José J F Raposo
Schwarzbold, Alexandre V
Zilli, Alexandre
Amazonas, Roberto B
Moreira, Frederico R
Alves, Lucas B O
Assis, Silvia R L
Neves, Precil D M M
Matuoka, Jessica Y
Boszczowski, Icaro
Catarino, Daniela G M
Veiga, Viviane C
Azevedo, Luciano C P
Rosa, Regis G
Lopes, Renato D
Cavalcanti, Alexandre B
Berwanger, Otavio
author_sort Avezum, Álvaro
collection PubMed
description BACKGROUND: Previous Randomised controlled trials (RCT) evaluating chloroquine and hydroxychloroquine in non-hospitalised COVID-19 patients have found no significant difference in hospitalisation rates. However, low statistical power precluded definitive answers. METHODS: We conducted a multicenter, double-blind, RCT in 56 Brazilian sites. Adults with suspected or confirmed COVID-19 presenting with mild or moderate symptoms with ≤ 07 days prior to enrollment and at least one risk factor for clinical deterioration were randomised (1:1) to receive hydroxychloroquine 400 mg twice a day (BID) in the first day, 400 mg once daily (OD) thereafter for a total of seven days, or matching placebo. The primary outcome was hospitalisation due to COVID-19 at 30 days, which was assessed by an adjudication committee masked to treatment allocation and following the intention-to-treat (ITT) principle. An additional analysis was performed only in participants with SARS-CoV-2 infection confirmed by molecular or serology testing (modified ITT [mITT] analysis). This trial was registered at ClinicalTrials.gov, NCT04466540. FINDINGS: From May 12, 2020 to July 07, 2021, 1372 patients were randomly allocated to hydroxychloroquine or placebo. There was no significant difference in the risk of hospitalisation between hydroxychloroquine and placebo groups (44/689 [6·4%] and 57/683 [8·3%], RR 0·77 [95% CI 0·52–1·12], respectively, p=0·16), and similar results were found in the mITT analysis with 43/478 [9·0%] and 55/471 [11·7%] events, RR 0·77 [95% CI 0·53–1·12)], respectively, p=0·17. To further complement our data, we conducted a meta-analysis which suggested no significant benefit of hydroxychloroquine in reducing hospitalisation among patients with positive testing (69/1222 [5·6%], and 88/1186 [7·4%]; RR 0·77 [95% CI 0·57–1·04]). INTERPRETATION: In outpatients with mild or moderate forms of COVID-19, the use of hydroxychloroquine did not reduce the risk of hospitalisation compared to the placebo control. Our findings do not support the routine use of hydroxychloroquine for treatment of COVID-19 in the outpatient setting. FUNDING: COALITION COVID-19 Brazil and EMS.
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spelling pubmed-89682382022-03-31 Hydroxychloroquine versus placebo in the treatment of non-hospitalised patients with COVID-19 (COPE – Coalition V): A double-blind, multicentre, randomised, controlled trial Avezum, Álvaro Oliveira, Gustavo B F Oliveira, Haliton Lucchetta, Rosa C Pereira, Valéria F A Dabarian, André L D´O Vieira, Ricardo Silva, Daniel V Kormann, Adrian P M Tognon, Alexandre P De Gasperi, Ricardo Hernandes, Mauro E Feitosa, Audes D M Piscopo, Agnaldo Souza, André S Miguel, Carlos H Nogueira, Vinicius O Minelli, César Magalhães, Carlos C Morejon, Karen M L Bicudo, Letícia S Souza, Germano E C Gomes, Marco A M Fo, José J F Raposo Schwarzbold, Alexandre V Zilli, Alexandre Amazonas, Roberto B Moreira, Frederico R Alves, Lucas B O Assis, Silvia R L Neves, Precil D M M Matuoka, Jessica Y Boszczowski, Icaro Catarino, Daniela G M Veiga, Viviane C Azevedo, Luciano C P Rosa, Regis G Lopes, Renato D Cavalcanti, Alexandre B Berwanger, Otavio Lancet Reg Health Am Articles BACKGROUND: Previous Randomised controlled trials (RCT) evaluating chloroquine and hydroxychloroquine in non-hospitalised COVID-19 patients have found no significant difference in hospitalisation rates. However, low statistical power precluded definitive answers. METHODS: We conducted a multicenter, double-blind, RCT in 56 Brazilian sites. Adults with suspected or confirmed COVID-19 presenting with mild or moderate symptoms with ≤ 07 days prior to enrollment and at least one risk factor for clinical deterioration were randomised (1:1) to receive hydroxychloroquine 400 mg twice a day (BID) in the first day, 400 mg once daily (OD) thereafter for a total of seven days, or matching placebo. The primary outcome was hospitalisation due to COVID-19 at 30 days, which was assessed by an adjudication committee masked to treatment allocation and following the intention-to-treat (ITT) principle. An additional analysis was performed only in participants with SARS-CoV-2 infection confirmed by molecular or serology testing (modified ITT [mITT] analysis). This trial was registered at ClinicalTrials.gov, NCT04466540. FINDINGS: From May 12, 2020 to July 07, 2021, 1372 patients were randomly allocated to hydroxychloroquine or placebo. There was no significant difference in the risk of hospitalisation between hydroxychloroquine and placebo groups (44/689 [6·4%] and 57/683 [8·3%], RR 0·77 [95% CI 0·52–1·12], respectively, p=0·16), and similar results were found in the mITT analysis with 43/478 [9·0%] and 55/471 [11·7%] events, RR 0·77 [95% CI 0·53–1·12)], respectively, p=0·17. To further complement our data, we conducted a meta-analysis which suggested no significant benefit of hydroxychloroquine in reducing hospitalisation among patients with positive testing (69/1222 [5·6%], and 88/1186 [7·4%]; RR 0·77 [95% CI 0·57–1·04]). INTERPRETATION: In outpatients with mild or moderate forms of COVID-19, the use of hydroxychloroquine did not reduce the risk of hospitalisation compared to the placebo control. Our findings do not support the routine use of hydroxychloroquine for treatment of COVID-19 in the outpatient setting. FUNDING: COALITION COVID-19 Brazil and EMS. Elsevier 2022-03-31 /pmc/articles/PMC8968238/ /pubmed/35378952 http://dx.doi.org/10.1016/j.lana.2022.100243 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Articles
Avezum, Álvaro
Oliveira, Gustavo B F
Oliveira, Haliton
Lucchetta, Rosa C
Pereira, Valéria F A
Dabarian, André L
D´O Vieira, Ricardo
Silva, Daniel V
Kormann, Adrian P M
Tognon, Alexandre P
De Gasperi, Ricardo
Hernandes, Mauro E
Feitosa, Audes D M
Piscopo, Agnaldo
Souza, André S
Miguel, Carlos H
Nogueira, Vinicius O
Minelli, César
Magalhães, Carlos C
Morejon, Karen M L
Bicudo, Letícia S
Souza, Germano E C
Gomes, Marco A M
Fo, José J F Raposo
Schwarzbold, Alexandre V
Zilli, Alexandre
Amazonas, Roberto B
Moreira, Frederico R
Alves, Lucas B O
Assis, Silvia R L
Neves, Precil D M M
Matuoka, Jessica Y
Boszczowski, Icaro
Catarino, Daniela G M
Veiga, Viviane C
Azevedo, Luciano C P
Rosa, Regis G
Lopes, Renato D
Cavalcanti, Alexandre B
Berwanger, Otavio
Hydroxychloroquine versus placebo in the treatment of non-hospitalised patients with COVID-19 (COPE – Coalition V): A double-blind, multicentre, randomised, controlled trial
title Hydroxychloroquine versus placebo in the treatment of non-hospitalised patients with COVID-19 (COPE – Coalition V): A double-blind, multicentre, randomised, controlled trial
title_full Hydroxychloroquine versus placebo in the treatment of non-hospitalised patients with COVID-19 (COPE – Coalition V): A double-blind, multicentre, randomised, controlled trial
title_fullStr Hydroxychloroquine versus placebo in the treatment of non-hospitalised patients with COVID-19 (COPE – Coalition V): A double-blind, multicentre, randomised, controlled trial
title_full_unstemmed Hydroxychloroquine versus placebo in the treatment of non-hospitalised patients with COVID-19 (COPE – Coalition V): A double-blind, multicentre, randomised, controlled trial
title_short Hydroxychloroquine versus placebo in the treatment of non-hospitalised patients with COVID-19 (COPE – Coalition V): A double-blind, multicentre, randomised, controlled trial
title_sort hydroxychloroquine versus placebo in the treatment of non-hospitalised patients with covid-19 (cope – coalition v): a double-blind, multicentre, randomised, controlled trial
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968238/
https://www.ncbi.nlm.nih.gov/pubmed/35378952
http://dx.doi.org/10.1016/j.lana.2022.100243
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