A multicenter, randomized, open-label, controlled trial to evaluate the efficacy and tolerability of hydroxychloroquine and a retrospective study in adult patients with mild to moderate coronavirus disease 2019 (COVID-19)

Abstract

Objective: In this study, we evaluated the efficacy of hydroxychloroquine (HCQ) against coronavirus disease 2019 (COVID-19) via a randomized controlled trial (RCT) and a retrospective study.

Methods: Subjects admitted to 11 designated public hospitals in Taiwan between April 1 and May 31, 2020, with COVID-19 diagnosis confirmed by pharyngeal real-time RT-PCR for SARS-CoV-2, were randomized at a 2:1 ratio and stratified by mild or moderate illness. HCQ (400 mg twice for 1 d or HCQ 200 mg twice daily for 6 days) was administered. Both the study and control group received standard of care (SOC). Pharyngeal swabs and sputum were collected every other day. The proportion and time to negative viral PCR were assessed on day 14. In the retrospective study, medical records were reviewed for patients admitted before March 31, 2020.

Results: There were 33 and 37 cases in the RCT and retrospective study, respectively. In the RCT, the median times to negative rRT-PCR from randomization to hospital day 14 were 5 days (95% CI; 1, 9 days) and 10 days (95% CI; 2, 12 days) for the HCQ and SOC groups, respectively (p = 0.40). On day 14, 81.0% (17/21) and 75.0% (9/12) of the subjects in the HCQ and SOC groups, respectively, had undetected virus (p = 0.36). In the retrospective study, 12 (42.9%) in the HCQ group and 5 (55.6%) in the control group had negative rRT-PCR results on hospital day 14 (p = 0.70).

Conclusions: Neither study demonstrated that HCQ shortened viral shedding in mild to moderate COVID-19 subjects.

Fig 1

Patient disposition in the multicenter, open-label, randomized controlled trial (a) and the retrospective study (b) of hydroxychloroquine. Abbreviations: HCQ: hydroxychloroquine; SOC: standard of care.

Fig 2. Probabilities of non-negative responses vs. time (days) for subjects in the HCQ and SOC groups in the multicenter, open-label, randomized controlled trial.

Abbreviations: HCQ: hydroxychloroquine; SOC: standard of care.

Fig 3. Mean Ct value of viral rRT-PCR vs. time (days) for subjects in the HCQ and SOC groups in the multicenter, open-label, randomized controlled trial.

Abbreviations: Ct: Cycle threshold; HCQ: hydroxychloroquine; rRT-PCR: real-time reverse transcription polymerase chain reaction; SOC: standard of care.