Hydroxychloroquine/chloroquine For The Treatment Of Hospitalized Patients With Covid-19: An Individual Participant Data Meta-analysis
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.
Stefano, Leon Di; Ogburn, Elizabeth L.; Ram, Malathi; Scharfstein, Daniel O.; Li, Tianjing; Khanal, Preeti; Baksh, Sheriza N.; McBee, Nichol; Gruber, Joshua; Gildea, Marianne R.; Clark, Megan R.; Goldenberg, Neil A.; Bennani, Yussef; Brown, Samuel M.; Buckel, Whitney R.; Clement, Meredith E.; Mulligan, Mark J.; O’Halloran, Jane A.; Rauseo, Adriana M.; Self, Wesley H.; Semler, Matthew W.; Seto, Todd; Stout, Jason E.; Ulrich, Robert J.; Victory, Jennifer; Bierer, Barbara E.; Hanley, Daniel F.; and Freilich, Daniel, "Hydroxychloroquine/chloroquine For The Treatment Of Hospitalized Patients With Covid-19: An Individual Participant Data Meta-analysis" (2022). School of Medicine Faculty Publications. 578.