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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

Avezum et al., The Lancet Regional Health - Americas, doi:10.1016/j.lana.2022.100243, NCT04466540
Mar 2022  
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Mortality 1% Improvement Relative Risk Mortality (b) -56% Ventilation -32% ICU admission 16% Hospitalization 23% Hospitalization (b) 40% HCQ  Avezum et al.  EARLY TREATMENT  DB RCT Is early treatment with HCQ beneficial for COVID-19? Double-blind RCT 1,372 patients in Brazil (May 2020 - July 2021) Lower hospitalization with HCQ (not stat. sig., p=0.18) c19hcq.org Avezum et al., The Lancet Regional Hea.., Mar 2022 FavorsHCQ Favorscontrol 0 0.5 1 1.5 2+
HCQ for COVID-19
1st treatment shown to reduce risk in March 2020, now with p < 0.00000000001 from 419 studies, recognized in 46 countries.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 112 treatments. c19hcq.org
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 et al. the median delay from onset was 7 days. Omrani et al. is missing. The values for Johnston et al. are incorrect - the study shows 4 hospitalizations in the control arm - RR for this study should be 0.58 instead of 0.78.
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).
This PaperHCQAll
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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