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

Avezum et al., The Lancet Regional Health - Americas, doi:10.1016/j.lana.2022.100243, NCT04466540

Mar 2022

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Authors have not responded to a request for the data.

Outpatient RCT with 687 HCQ and 682 control patients in Brazil, showing lower hospitalization with treatment, not reaching statistical significance. Higher efficacy was seen with treatment <4 days from onset, RR 0.61. The associated meta analysis includes mostly late treatment studies, for example in Schwartz the median delay from onset was 7 days. Omrani is missing. The values for Johnston are incorrect - the study shows 4 hospitalizations in the control arm - RR for this study should be 0.58 instead of 0.78.

1. Johnston et al., Hydroxychloroquine with or Without Azithromycin for Treatment of Early SARS-CoV-2 Infection Among High-Risk Outpatient Adults: A Randomized Clinical Trial, EClinicalMedicine, doi:10.1016/j.eclinm.2021.100773.thelancet.com, doi.org.

2. Omrani et al., Randomized double-blinded placebo-controlled trial of hydroxychloroquine with or without azithromycin for virologic cure of non-severe Covid-19, EClinicalMedicine, doi:10.1016/j.eclinm.2020.100645.sciencedirect.com, doi.org.

3. Schwartz et al., Assessing the efficacy and safety of hydroxychloroquine as outpatient treatment of COVID-19: a randomized controlled trial, CMAJ Open, doi:10.9778/cmajo.20210069.cmajopen.ca, doi.org.

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risk of death, 0.7% lower, RR 0.99, p = 1.00, treatment 5 of 687 (0.7%), control 5 of 682 (0.7%), NNT 18741, all-cause death.

risk of death, 56.0% higher, HR 1.56, p = 0.54, treatment 5 of 687 (0.7%), control 5 of 682 (0.7%), adjusted per study, univariate Firth's penalized likelihood.

risk of mechanical ventilation, 32.4% higher, RR 1.32, p = 0.79, treatment 8 of 687 (1.2%), control 6 of 682 (0.9%).

risk of ICU admission, 16.4% lower, RR 0.84, p = 0.61, treatment 16 of 687 (2.3%), control 19 of 682 (2.8%), NNT 219.

risk of hospitalization, 23.5% lower, RR 0.77, p = 0.18, treatment 44 of 689 (6.4%), control 57 of 683 (8.3%), NNT 51.

risk of hospitalization, 40.0% lower, RR 0.60, p = 0.15, treatment 267, control 265, <4 days.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Avezum et al., 31 Mar 2022, Double Blind Randomized Controlled Trial, Brazil, peer-reviewed, 40 authors, study period 12 May, 2020 - 7 July, 2021, average treatment delay 4.0 days, dosage 400mg bid day 1, 200mg bid days 2-7, trial NCT04466540 (history).

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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

Álvaro Avezum, Gustavo B F Oliveira, Haliton Oliveira, Rosa C Lucchetta, Valéria F A Pereira, André L Dabarian, Ricardo D´o Vieira, Daniel V Silva, Adrian P M Kormann, Alexandre P Tognon, Ricardo De Gasperi, Mauro E Hernandes, Audes D M Feitosa, Agnaldo Piscopo, André S Souza, Carlos H Miguel, Vinicius O Nogueira, César Minelli, Carlos C Magalhães, Karen M L Morejon, Letícia S Bicudo, Germano E C Souza, Marco A M Gomes, José J F Raposo Fo, Alexandre V Schwarzbold, Alexandre Zilli, Roberto B Amazonas, Frederico R Moreira, Lucas B O Alves, Silvia R L Assis, Precil D M M Neves, Jessica Y Matuoka, Icaro Boszczowski, Daniela G M Catarino, Viviane C Veiga, Luciano C P Azevedo, Regis G Rosa, Renato D Lopes, Alexandre B Cavalcanti, Otavio Berwanger

The Lancet Regional Health - Americas, doi:10.1016/j.lana.2022.100243

Background Previous Randomised controlled trials (RCT) evaluating chloroquine and hydroxychloroquine in nonhospitalised COVID-19 patients have found no significant difference in hospitalisation rates. However, low statistical power precluded definitive answers.

Supplementary materials Supplementary material associated with this article can be found in the online version at doi:10.1016/j. lana.2022.100243.

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