Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials

Axfors C, Schmitt AM, Janiaud P, van’t Hooft J, Abd-Elsalam S, Abdo EF, Abella BS, Akram J, Amaravadi RK, Angus DC, Arabi YM, Azhar S, Baden LR, Baker AW, Belkhir L, Benfield T, Berrevoets MAH, Chen CP, Chen TC, Cheng SH, Cheng CY, Chung WS, Cohen YZ, Cowan LN, Dalgard O, de Almeida e Val FF, de Lacerda MVG, de Melo GC, Derde L, Dubee V, Elfakir A, Gordon AC, Hernandez-Cardenas CM, Hills T, Hoepelman AIM, Huang YW, Igau B, Jin R, Jurado-Camacho F, Khan KS, Kremsner PG, Kreuels B, Kuo CY, Le T, Lin YC, Lin WP, Lin TH, Lyngbakken MN, McArthur C, McVerry BJ, Meza-Meneses P, Monteiro WM, Morpeth SC, Mourad A, Mulligan MJ, Murthy S, Naggie S, Narayanasamy S, Nichol A, Novack LA, O’Brien SM, Okeke NL, Perez L, Perez-Padilla R, Perrin L, Remigio-Luna A, Rivera-Martinez NE, Rockhold FW, Rodriguez-Llamazares S, Rolfe R, Rosa R, Røsjø H, Sampaio VS, Seto TB, Shehzad M, Soliman S, Stout JE, Thirion-Romero I, Troxel AB, Tseng TY, Turner NA, Ulrich RJ, Walsh SR, Webb SA, Weehuizen JM, Velinova M, Wong HL, Wrenn R, Zampieri FG, Zhong W, Moher D, Goodman SN, Ioannidis JPA, Hemkens LG

Nat Commun 12 (1) 2349 [2021-12-00; online 2021-04-15]

Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/ ). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.

Category: Biochemistry

Category: Drug Discovery

Type: Journal article

PubMed 33859192

DOI 10.1038/s41467-021-22446-z

Crossref 10.1038/s41467-021-22446-z

Coded data from each included study and data analysis code


Publications 7.1.2