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

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

Published version (DOI) Open Access Copy (Duke) Link to item

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of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished.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 We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed,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 We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients).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

Duke Scholars

Author Arthur Wakefield Baker Medicine, Infectious Diseases

Author Thuy Le Medicine, Infectious Diseases

Author Ahmad Mourad Medicine, Infectious Diseases

Author Susanna Naggie Medicine, Infectious Diseases

Author Shanti Narayanasamy Duke Global Health Institute

Author Sean Michael O'Brien Biostatistics & Bioinformatics, Division of Biostatistics

Author Nwora Lance Okeke Medicine, Infectious Diseases

Author Frank Wesley Rockhold Biostatistics & Bioinformatics, Division of Biostatistics

Author Jason Eric Stout Medicine, Infectious Diseases

Author Nicholas Turner Medicine, Infectious Diseases

Published In

Nat Commun

DOI

10.1038/s41467-021-22446-z

EISSN

2041-1723

Publication Date

April 15, 2021

Volume

Issue

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

APA

Chicago

ICMJE

MLA

NLM

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

10.1038/s41467-021-22446-z

EISSN

2041-1723

Publication Date

April 15, 2021

Volume

Issue

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