PLoS ONE (Jan 2022)

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. Self,
  • Matthew W. Semler,
  • Todd Seto,
  • Jason E. Stout,
  • Robert J. Ulrich,
  • Jennifer Victory,
  • Barbara E. Bierer,
  • Daniel F. Hanley,
  • Daniel Freilich

Journal volume & issue
Vol. 17, no. 9

Abstract

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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.