Hydroxychloroquine plus azithromycin early treatment of mild COVID-19 in an outpatient setting: a randomized, double-blinded, placebo-controlled clinical trial evaluating viral clearance
Cristhieni Rodrigues, Rodrigo S Freitas-Santos, José Eduardo Levi, Andreza A Senerchia, Ana Tarina A Lopes, Sergio R Santos, Rinaldo F Siciliano, Lígia C Pierrotti
International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2021.106428
Background: Hydroxychloroquine has shown potential to block viral replication of SARS-CoV-2 in some in vitro studies. This randomised, double-blinded, placebo controlled clinical trial evaluated the efficacy of hydroxychloroquine plus azithromycin (HCQ/AZT) in reducing viral loads in patients with early and mild SARS-CoV-2 infection. Methods: A single-centre randomised placebo-controlled clinical trial was conducted with outpatients with early and mild SARS-CoV-2 infection. Inclusion criteria were: patients aged 18-65 years with symptoms suggestive of COVID-19 for < 5 days, no significant comorbidities, and positive nasopharyngeal/oropharyngeal swab screening tests (POCT-PCR). Randomised patients received either hydroxychloroquine for 7 days plus azithromycin for 5 days or placebo. The primary endpoint was viral clearance within a 9-day period. Secondary endpoints included viral load reduction, clinical evolution, hospitalization rates, chest computed tomography evolution, and adverse effects. Results: From 107 potential trial participants, 84 were enrolled following predetermined criteria. Statistical analyses were performed on an intention-to-treat (N = 84) and per-protocol (PP) basis (N = 70). On the PP analysis, the treatment (N = 36) and placebo (N = 34) groups displayed similar demographic characteristics. At 95% CI, no statistically significant between-group differences were found in viral clearance rates within 9 days following enrolment ( P = 0.26). Conclusions: This randomised, double-blinded, placebo-controlled clinical trial evaluating outpatients with early and mild COVID-19 showed that viral clearance rates within a 9-day period from enrolment did not change with HCQ/AZT treatment compared with placebo, although no major cardiovascular events were observed in participants without comorbidities. Secondary outcomes were also not significantly improved with HCQ/AZT treatment compared with placebo. These findings do not support use of HCQ/AZT in this setting.
DECLARATIONS Funding: This study was funded by Diagnósticos da América S.A. (Dasa), Ímpar Serviços Hospitalares S.A., and DNA Capital Foundation. Competing Interests: All authors report no conflicts of interest relevant to this article. Ethical Approval: The present study was designed as a prospective, double blinded, placebo-controlled, randomised clinical trial, in accordance with The Consolidated Standards of Reporting Trials (CONSORT) Statement, approved by the local ethics and research committee, registered at REBEC (30413020.8.0 0 0 0.0 0 08),
Supplementary materials Supplementary material associated with this article can be found, in the online version, at doi: 10.1016/j.ijantimicag.2021. 106428 .
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