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

Publication ,  Journal Article
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; Le, T ...
Published in: Nat Commun
April 15, 2021

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of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished.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 We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed,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 We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients).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.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

April 15, 2021

Volume

12

Issue

1

Start / End Page

2349

Location

England

Related Subject Headings

  • SARS-CoV-2
  • Randomized Controlled Trials as Topic
  • Pregnancy Complications, Infectious
  • Pregnancy
  • Patient Participation
  • Odds Ratio
  • International Cooperation
  • Hydroxychloroquine
  • Humans
  • Female
 

Citation

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Chicago
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Axfors, C., Schmitt, A. M., Janiaud, P., Van’t Hooft, J., Abd-Elsalam, S., Abdo, E. F., … Hemkens, L. G. (2021). Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials. Nat Commun, 12(1), 2349. https://doi.org/10.1038/s41467-021-22446-z
Axfors, Cathrine, Andreas M. Schmitt, Perrine Janiaud, Janneke Van’t Hooft, Sherief Abd-Elsalam, Ehab F. Abdo, Benjamin S. Abella, et al. “Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials.Nat Commun 12, no. 1 (April 15, 2021): 2349. https://doi.org/10.1038/s41467-021-22446-z.
Axfors C, Schmitt AM, Janiaud P, Van’t Hooft J, Abd-Elsalam S, Abdo EF, et al. Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials. Nat Commun. 2021 Apr 15;12(1):2349.
Axfors, Cathrine, et al. “Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials.Nat Commun, vol. 12, no. 1, Apr. 2021, p. 2349. Pubmed, doi:10.1038/s41467-021-22446-z.
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 C-P, Chen T-C, Cheng S-H, Cheng C-Y, Chung W-S, 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 Y-W, Igau B, Jin R, Jurado-Camacho F, Khan KS, Kremsner PG, Kreuels B, Kuo C-Y, Le T, Lin Y-C, Lin W-P, Lin T-H, 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, Shahzad M, Soliman S, Stout JE, Thirion-Romero I, Troxel AB, Tseng T-Y, Turner NA, Ulrich RJ, Walsh SR, Webb SA, Weehuizen JM, Velinova M, Wong H-L, Wrenn R, Zampieri FG, Zhong W, Moher D, Goodman SN, Ioannidis JPA, Hemkens LG. Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials. Nat Commun. 2021 Apr 15;12(1):2349.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

April 15, 2021

Volume

12

Issue

1

Start / End Page

2349

Location

England

Related Subject Headings

  • SARS-CoV-2
  • Randomized Controlled Trials as Topic
  • Pregnancy Complications, Infectious
  • Pregnancy
  • Patient Participation
  • Odds Ratio
  • International Cooperation
  • Hydroxychloroquine
  • Humans
  • Female