Efficacy and safety of favipiravir in a complex therapy of mild to moderate COVID-19

Abstract

Aim of the study – to assess the efficacy and safety of favipiravir for treatment of mild to moderate coronavirus disease (COVID-19). Material and methods. An open-labeled, randomized, active-controlled multicenter trial of favipiravir in out- and hospitalized patients with mild to moderate COVID-19 was conducted. Eligible patients were aged 18–60 years and had laboratory confirmed by PCR test infection of SARS-CoV-2. Patients were randomly assigned in a 2:1 ratio to receive either favipiravir (1800 mg BID on day 1, followed by 800 mg BID for 9 days), or standard of care (SOC) treatment (umifenovir + intranasal interferon alpha-2b, or hydroxychloroquine for up to 10 days). In needed, patients received concomitant symptomatic medication. The co-primary outcomes were the time to clinical improvement and the time to viral clearance. Results and discussion. It was found that the median time to clinical improvement was 6.0 [interquartile range (IQR) 4.0; 9.3] days in favipiravir group and 10.0 (IQR 5.0; 21.0) days in SOC group; the median difference was 4 days [hazard ratio (HR) 1.63; 95% confidence interval (CI) 1.14–2.34, p=0.007]. The rate of clinical improvement in the favipiravir group on day 7 was 1.5-fold higher compared to SOC: 52.7% vs 35.7% [risk ratio (RR) 1.50; 95% CI 1.02–2.22; p=0.020]. Despite an absence of statistically significant difference between the median time to viral elimination, the rates of viral elimination on day 3 and day 5 were significantly higher in favipiravir group: on the day 3 viral elimination was observed for in 71.4% of patients, who received favipiravir vs 57.1% in SOC group (RR 1.27; 95% CI 0.99–1.64; p=0.030), on the day 5 81.2 vs 67.9%, respectively (RR 1.22; 95% CI 1.00–1.48; р=0.022). Favipiravir was well tolerated: most of the adverse events (AE) were mild. The most common AEs were asymptomatic hyperuricemia, transient elevation of ALT & AST, and gastrointestinal disorders (diarrhea, nausea, abdominal pain). This study confirmed the superiority of favipiravir vs standard ethiotropic therapy in treatment of patients with mild to moderate COVID-19.