Hydroxychloroquine for SARS-CoV-2 positive patients quarantined at home: The first interim analysis of a remotely conducted randomized clinical trial

Amaravadi, R.; Giles, L.; Carberry, M.; Hyman, M. C.; Frank, I.; Nasta, S.; Walsh, J.; Wileyto, E. P.; Gimotty, P.; Milone, M.; Teng, E.; Vyas, N.; Balian, S.; Kolansky, J.; Abdulhay, N.; Mcgovern, S.; Gamblin, S.; Doran, O.; Callahan, P.; Abella, B.

ABSTRACT Background Older patients are at risk of increased morbidity and mortality from COVID-19 disease due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There are few effective treatments for outpatients with COVID-19. Objective To evaluate the efficacy of hydroxychloroquine to reduce time in quarantine for symptomatic [≥]40 years-old COVID-19 patients. Design A randomized, double-blind, placebo-controlled clinical trial. Setting Outpatients with polymerase chain reaction confirmed COVID-19 at a University of Pennsylvania affiliated testing center between April 15, 2020 and, July 14, 2020. Participants Out of 5511 SARS-CoV-2 positive patients, 1072 met initial eligibility criteria for telephonebased recruitment, but only 34 subjects were able to be randomized. Interventions Hydroxychloroquine 400 mg per twice daily (n=17) or matching placebo (n=17), taken orally for up to 14 days. Measurements The primary outcome was the time to release from quarantine. Secondary outcomes included the participant-reported secondary infection of co-inhabitants, hospitalization, treatment-related adverse events, time to symptom improvement, and incidence of cardiac arrhythmia. Results Amaravadi et al - Trial of hydroxychloroquine for outpatient treatment of COVID-19 3 The median time to release from quarantine for HCQ-treated vs. placebo-treated participants was 8 days (range 4-19 days) vs. 11 days (4-18 days); z-score +0.58, p=n.s. This did not meet the pre-specified criteria for early termination, however, this study was terminated early due to lack of feasibility. There was no mortality in either study arm. Limitation Since this study was terminated early due to a lack of feasibility, no conclusion can be made about the efficacy of hydroxychloroquine as a treatment for COVID-19 patients 40 years of age or older quarantined at home. Conclusion The design of this remotely conducted study could guide testing of other more promising agents during the COVID-19 pandemic.