Hydroxychloroquine/chloroquine for the treatment of hospitalized patients with COVID-19: An individual participant data meta-analysis.
Journal Article (Journal Article)
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.
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- Di Stefano, L; Ogburn, EL; Ram, M; Scharfstein, DO; Li, T; Khanal, P; Baksh, SN; McBee, N; Gruber, J; Gildea, MR; Clark, MR; Goldenberg, NA; Bennani, Y; Brown, SM; Buckel, WR; Clement, ME; Mulligan, MJ; O'Halloran, JA; Rauseo, AM; Self, WH; Semler, MW; Seto, T; Stout, JE; Ulrich, RJ; Victory, J; Bierer, BE; Hanley, DF; Freilich, D; Pandemic Response COVID-19 Research Collaboration Platform for HCQ/CQ Pooled Analyses,
Volume / Issue
- 17 / 9
Start / End Page
- e0273526 -
Pubmed Central ID
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Digital Object Identifier (DOI)
- United States