E-DRUG: Mortality outcomes with hydroxychloroquine & chloroquine in
COVID-19 international collaborative meta-analysis of randomized trials
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[This is a meta-analysis including data from the WHO SOLIDARITY trial and
the UK RECOVERY trial of different drugs to treat covid-19 illness. Can the
use of hydroxychloroquine and chloroquine now stop please. Enough people
have suffered unnecessarily. Kirsten]
Nature Communications open access
https://www.nature.com/articles/s41467-021-22446-z.pdf
Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from
an international collaborative meta-analysis of randomized trials
Abstract
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and unpublished.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We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO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. Pre-specified 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 We included 14 unpublished trials (1308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.
Name of all contributors appear at the end of the article.
Kirsten
Ms Kirsten Myhr, MScPharm, MPH
Kongsberg, Norway
myhr[at]online.no