Hydroxychloroquine plus azithromycin early treatment of mild COVID-19 in outpatient setting: a randomized, double-blinded, placebo-controlled clinical trial evaluating viral clearance

Rodrigues, Cristhieni; Freitas-Santos, Rodrigo S; Levi, José Eduardo; Senerchia, Andreza A; Lopes, Ana Tarina A; Santos, Sergio R; Siciliano, Rinaldo F; Pierrotti, Lígia C

BACKGROUND: : Hydroxychloroquine showed potential to block viral replication of SARS-CoV-2 in in vitro studies. This randomized, double-blinded, placebo controlled clinical trial evaluated the efficacy of hydroxychloroquine plus azithromycin in reducing viral loads in patients with early and mild SARS-CoV-2 infection. METHODS: : A single-center randomized placebo-controlled clinical trial involving outpatients with early and mild SARS-CoV-2 infection was conducted. Inclusion criteria: patients aged between 18 to 65 years with symptoms suggestive of COVID-19 for fewer than five days, no significant comorbidities, and positive naso/oropharyngeal swab screening tests (POCT-PCR). Randomized patients received either hydroxychloroquine for seven days plus azithromycin for five 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 pre-determined 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 group (N=36) and the placebo group (N=34) displayed similar demographic characteristics. At 95% CI, no statistically significant differences were found between groups in viral clearance rates within a 9-day following enrollment (p-value 0.26). CONCLUSIONS: : Among outpatients with early and mild COVID-19, the use of HCQ/AZT did not impact the time to viral clearance compared to placebo. Secondary outcomes were also not significantly improved with HCQ/AZT treatment compared to placebo. These findings do not support use of HCQ/AZT in this setting.