Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials release_3b6sqsfu55gqzcncxivd4lyulu

by Cathrine Axfors, Andreas Schmitt, Perrine Janiaud, Janneke van 't Hooft, sherief abd-elsalam, Ehab Moustafa, Benjamin Abella, Javed Akram, Ravi K. Amaravadi, Derek C. Angus, Yaseen M. Arabi, Shehnoor Azhar (+82 others)

Published in Nature Communications by Springer Science and Business Media LLC.

Volume 12, Issue 1 p2349 (2021)

Abstract

<jats:title>Abstract</jats:title>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of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished.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: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://osf.io/QESV4/">https://osf.io/QESV4/</jats:ext-link>). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed,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 We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients).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.
In application/xml+jats format

Archived Files and Locations

application/pdf  1.7 MB
file_epqbbz3qyrfg5d4pt3jaohalue
web.archive.org (webarchive)
www.nature.com (publisher)
Read Archived PDF
Archived
Type  article-journal
Stage   published
Date   2021-04-15
Language   en ?
Container Metadata
Open Access Publication
In DOAJ
In Keepers Registery
ISSN-L:  2041-1723
Work Entity
access all versions, variants, and formats of this works (eg, pre-prints)
Catalog Record
Revision: 3f883aad-5745-471a-9c3c-855fe049b9c2
API URL: JSON