Abstract: ORIGINAL RESEARCH ARTICLES Hydroxychloroquine in Hospitalized Patients with COVID-19: Real-World Experience Assessing Mortality Frank H. Annie, Cristian Sirbu, Keely R. Frazier, Mike Broce, and B. Daniel Lucas Jr. Charleston Area Medical Center Health Education and Research Institute, Charleston, West Virginia, INTRODUCTION Hydroxychloroquine (HCQ) for coronavirus disease 2019 (COVID-19) is presently being used off-label or within a clinical trial. OBJECTIVES We investigated a multinational database of patients with COVID-19 with real-world data containing outcomes and their relationship to HCQ use. The primary outcome was all-cause mortality within 30 days of follow-up. METHODS This was a retrospective cohort study of patients receiving HCQ within 48 hours of hospital admission. Medications, preexisting conditions, clinical measures on admission, and outcomes were recorded. RESULTS Among patients with a diagnosis of COVID-19 in our propensity-matched cohort, the mean ages  SD were 62.3  15.9 years (53.7% male) and 61.9  16.0 years (53.0% male) in the HCQ and no-HCQ groups, respectively. There was no difference in overall 30-day mortality between the HCQ and no-HCQ groups (HCQ 13.1%, n=367; no HCQ 13.6%, n=367; odds ratio 0.95, 95% confidence interval 0.62–1.46) after propensity matching. Although statistically insignificant, the HCQazithromycin (AZ) group had an overall mortality rate of 14.6% (n=199) compared with propensitymatched no-HCQ–AZ cohort’s rate of 12.1% (n=199, OR 1.24, 95% CI 0.70–2.22). Importantly, however, there was no trend in this cohort’s overall mortality/arrhythmogenesis outcome (HCQ-AZ 17.1%, no HCQ–no AZ 17.1%; OR 1.0, 95% CI 0.6–1.7). CONCLUSIONS We report from a large retrospective multinational database analysis of COVID-19 outcomes with HCQ and overall mortality in hospitalized patients. There was no statistically significant increase in mortality and mortality-arrhythmia with HCQ or HCQ-AZ. KEY WORDS Antimalarial, azithromycin, coronavirus, hydroxychloroquine, macrolide, severe acute respiratory syndrome coronavirus 2. (Pharmacotherapy 2020;40(11):1072–1081) doi: 10.1002/phar.2467 The search for safe and effective coronavirus disease 2019 (COVID-19) therapies has accelerated at a frenzied pace. Having advocated for clinicaltrials.gov use in the search for alternative approaches to the patient with COVID-19,1 searching within the database revealed 3185 COVID-19 clinical trials as of August 31, 2020. Conflict of interest: The authors declare no conflicts of interest. *Address for correspondence: B. Daniel Lucas Jr., CAMC Health Education and Research Institute, 3200 MacCorkle Avenue, Charleston, WV 25304; e-mail: dan.lucas@camc.org. Ó 2020 Pharmacotherapy Publications, Inc. Of these registered COVID-19 clinical trials, 1792 appeared to be treatment trials. Repurposed hydroxychloroquine (HCQ) in prospective randomized clinical trials accounted for 251 of these registered trials with completion dates ranging from February 2020 to December 2029. Presently, HCQ for COVID-19 is being used offlabel or within one of these clinical trials. Although understanding HCQ’s efficacy profile in COVID-19 is an immediate concern, its safety profile has dominated recent public conversation. Indeed, the United States Food and Drug Administration issued additional safety guidance for use of HCQ after the original, now HYDROXYCHLOROQUINE IN PATIENTS WITH COVID-19 Annie et al withdrawn, emergency use authorization,2..