Efficacy and safety of favipiravir, an oral RNA-dependent RNA polymerase inhibitor, in mild-to-moderate COVID-19: A randomized, comparative, open-label, multicenter, phase 3 clinical trial

Int J Infect Dis. 2021 Feb;103:62-71. doi: 10.1016/j.ijid.2020.11.142. Epub 2020 Nov 16.

Abstract

Objective: To assess the efficacy and safety of favipiravir in adults with mild-to-moderate coronavirus disease 2019 (COVID-19).

Methods: In this randomized, open-label, parallel-arm, multicenter, phase 3 trial, adults (18-75 years) with RT-PCR confirmed COVID-19 and mild-to-moderate symptoms (including asymptomatic) were randomized 1:1 to oral favipiravir (day 1: 1800 mg BID and days 2-14: 800 mg BID) plus standard supportive care versus supportive care alone. The primary endpoint was time to the cessation of viral shedding; time to clinical cure was also measured.

Results: From May 14 to July 3, 2020, 150 patients were randomized to favipiravir (n = 75) or control (n = 75). Median time to the cessation of viral shedding was 5 days (95% CI: 4 days, 7 days) versus 7 days (95% CI: 5 days, 8 days), P = 0.129, and median time to clinical cure was 3 days (95% CI: 3 days, 4 days) versus 5 days (95% CI: 4 days, 6 days), P = 0.030, for favipiravir and control, respectively. Adverse events were observed in 36% of favipiravir and 8% of control patients. One control patient died due to worsening disease.

Conclusion: The lack of statistical significance on the primary endpoint was confounded by limitations of the RT-PCR assay. Significant improvement in time to clinical cure suggests favipiravir may be beneficial in mild-to-moderate COVID-19.

Keywords: Antiviral; COVID-19; Coronavirus; Favipiravir; Randomized clinical trial; SARS-CoV-2.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Amides / adverse effects
  • Amides / therapeutic use*
  • COVID-19 / drug therapy*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pyrazines / adverse effects
  • Pyrazines / therapeutic use*
  • RNA-Dependent RNA Polymerase / antagonists & inhibitors*
  • SARS-CoV-2*
  • Young Adult

Substances

  • Amides
  • Pyrazines
  • RNA-Dependent RNA Polymerase
  • favipiravir

Supplementary concepts

  • COVID-19 drug treatment