Hydroxychloroquine use in hospitalised patients with COVID-19: An observational matched cohort study
Markos Kalligeros, Fadi Shehadeh, Eleftheria Atalla, Evangelia K Mylona, Su Aung, Aakriti Pandita, Jerry Larkin, Martha Sanchez, Francine Touzard-Romo, Amy Brotherton, Rajeev Shah, Cheston B Cunha, Eleftherios Mylonakis
Journal of Global Antimicrobial Resistance, doi:10.1016/j.jgar.2020.07.018
To assess the efficacy and safety of hydroxychloroquine with or without azithromycin) in hospitalized adult patients with COVID-19. Methods: We utilized a hospital based prospective data registry. The primary end point was to assess the impact of hydroxychloroquine with or without azithromycin, on outcome, length of hospitalization, and time to clinical improvement. We utilized treatment effects with inverse-probability-weighting and Cox proportional hazards models. All analyses accounted for age, gender, race, severity on admission, days from symptoms onset and chronic comorbidities. Results: 36 patients received hydroxychloroquine and were age-and sex-matched to 72 patients with COVID-19 who received supportive care. Compared to supportive care, the use of HCQ did not shorten the time to clinical improvement (+0.23 days; 95% CI: À1.8-2.3 days) nor did it shorten the duration of hospital stay (+0.91 days; 95% CI: À1.1-2.9 days). Additionally, HCQ did not decrease the risk of COVID-19 in-hospital death (aHR 1.67; 95% CI: 0.29-9.36). Finally, we observed a slight QTc prolongation from a baseline of 444 AE 26 ms to 464 AE 32 ms (meanAESD) among patients receiving hydroxychloroquine with or without azithromycin. Conclusion: This study did not yield benefits from hydroxychloroquine use in patients with COVID-19 and monitoring for adverse events is warranted. Nevertheless, the treatment was safely studied under the guidance of an antimicrobial stewardship program.
Ethical approval This study received ethical approval from the Institutional Review Board (IRB) of the Rhode Island Hospital (Providence, RI, USA) [ref. #005120].
Appendix A. Supplementary data Supplementary material related to this article can be found, in the online version, at doi:https://doi.org/10.1016/j.jgar.2020.07.018.
References
Geleris, Sun, Platt, Zucker, Baldwin et al., Observational study of hydroxychloroquine in hospitalized patients with COVID-19, N Engl J Med,
doi:10.1056/NEJMoa2012410
Magagnoli, Narendran, Pereira, Cummings, Hardin et al., Outcomes of hydroxychloroquine usage in United States veterans hospitalized with COVID-19, medRxiv,
doi:10.1101/2020.04.16.20065920
Mahevas, Tran, Roumier, Chabrol, Paule et al., No evidence of clinical efficacy of hydroxychloroquine in patients hospitalized for COVID-19 infection with oxygen requirement: results of a study using routinely collected data to emulate a target trial, medRxiv,
doi:10.1101/2020.04.10.20060699
Wang, Cao, Zhang, Yang, Liu et al., Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res,
doi:10.1038/s41422-020-0282-0
Yao, Ye, Zhang, Cui, Huang et al., In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Clin Infect Dis,
doi:10.1093/cid/ciaa237
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