Hydroxychloroquine/chloroquine for the treatment of hospitalized patients with COVID-19: An individual participant data meta-analysis

Leon Di Stefano, Elizabeth L. Ogburn, Malathi Ram, Daniel O. Scharfstein, Tianjing Li, Preeti Khanal, Sheriza N. Baksh, Nichol McBee, Joshua Gruber, Marianne R. Gildea, Megan R. Clark, Neil A. Goldenberg, Yussef Bennani, Samuel M. Brown, Whitney R. Buckel, Meredith E. Clement, Mark J. Mulligan, Jane A. O’Halloran, Adriana M. Rauseo, Wesley H. SelfMatthew W. Semler, Todd Seto, Jason E. Stout, Robert J. Ulrich, Jennifer Victory, Barbara E. Bierer, Daniel F. Hanley, Daniel Freilich

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4 Scopus citations


Background Results from observational studies and randomized clinical trials (RCTs) have led to the consensus that hydroxychloroquine (HCQ) and chloroquine (CQ) are not effective for COVID-19 prevention or treatment. Pooling individual participant data, including unanalyzed data from trials terminated early, enables more detailed investigation of the efficacy and safety of HCQ/CQ among subgroups of hospitalized patients. Methods We searched ClinicalTrials.gov in May and June 2020 for US-based RCTs evaluating HCQ/ CQ in hospitalized COVID-19 patients in which the outcomes defined in this study were recorded or could be extrapolated. The primary outcome was a 7-point ordinal scale measured between day 28 and 35 post enrollment; comparisons used proportional odds ratios. Harmonized de-identified data were collected via a common template spreadsheet sent to each principal investigator. The data were analyzed by fitting a prespecified Bayesian ordinal regression model and standardizing the resulting predictions. Results Eight of 19 trials met eligibility criteria and agreed to participate. Patient-level data were available from 770 participants (412 HCQ/CQ vs 358 control). Baseline characteristics were similar between groups. We did not find evidence of a difference in COVID-19 ordinal scores between days 28 and 35 post-enrollment in the pooled patient population (odds ratio, 0.97; 95% credible interval, 0.76–1.24; higher favors HCQ/CQ), and found no convincing evidence of meaningful treatment effect heterogeneity among prespecified subgroups. Adverse event and serious adverse event rates were numerically higher with HCQ/CQ vs control (0.39 vs 0.29 and 0.13 vs 0.09 per patient, respectively). Conclusions The findings of this individual participant data meta-analysis reinforce those of individual RCTs that HCQ/CQ is not efficacious for treatment of COVID-19 in hospitalized patients.

Original languageEnglish
Article numbere0273526
JournalPloS one
Issue number9 September
StatePublished - Sep 2022


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