Favipiravir for treatment of outpatients with asymptomatic or uncomplicated COVID-19: a double-blind randomized, placebo-controlled, phase 2 trial

  1. Marisa Holubar
  2. Aruna Subramanian
  3. Natasha Purington
  4. Haley Hedlin
  5. Bryan Bunning
  6. Katharine S. Walter
  7. Hector Bonilla
  8. Athanasia Boumis
  9. Michael Chen
  10. Kimberly Clinton
  11. Liisa Dewhurst
  12. Carol Epstein
  13. Prasanna Jagannathan
  14. Richard H. Kaszynski
  15. Lori Panu
  16. Julie Parsonnet
  17. Elizabeth L. Ponder
  18. Orlando Quintero
  19. Elizabeth Sefton
  20. Upinder Singh
  21. Luke Soberanis
  22. Henry Truong
  23. Jason R. Andrews
  24. Manisha Desai
  25. Chaitan Khosla
  26. Yvonne Maldonado
1 evaluations Published on
Read the full article Related papers
This article on Sciety

Abstract

Background

Favipiravir is an oral, RNA-dependent RNA polymerase inhibitor with in vitro activity against SARS-CoV2. Despite limited data, favipiravir is administered to patients with COVID-19 in several countries.

Methods

We conducted a phase 2 double-blind randomized controlled outpatient trial of favipiravir in asymptomatic or mildly symptomatic adults with a positive SARS-CoV2 RT-PCR within 72 hours of enrollment. Participants were randomized 1:1 to receive placebo or favipiravir (1800 mg BID Day 1, 800mg BID Days 2-10). The primary outcome was SARS-CoV-2 shedding cessation in a modified intention-to-treat (mITT) cohort of participants with positive enrollment RT-PCRs. Using SARS-CoV-2 deep sequencing, we assessed favipiravir’s impact on mutagenesis.

Results

From July 8, 2020 - March 23, 2021, we randomized 149 participants with 116 included in the mITT cohort. The participants’ mean age was 43 years (SD 12.5) and 57 (49%) were women. We found no difference in time to shedding cessation by treatment arm overall (HR 0.76 favoring placebo, 95% confidence interval [CI] 0.48 – 1.20) or in sub-group analyses (age, sex, high-risk comorbidities, seropositivity or symptom duration at enrollment). We observed no difference in time to symptom resolution (initial: HR 0.84, 95% CI 0.54 – 1.29; sustained: HR 0.87, 95% CI 0.52 – 1.45). We detected no difference in accumulation of transition mutations in the viral genome during treatment.

Conclusions

Our data do not support favipiravir use at commonly used doses in outpatients with uncomplicated COVID-19. Further research is needed to ascertain if higher doses of favipiravir are effective and safe for patients with COVID-19.

Trial registration number

NCT04346628

Summary

In this phase 2 double-blind randomized controlled outpatient trial of favipiravir in asymptomatic or uncomplicated patients with COVID-19, we found no difference in time to shedding cessation or time to symptom resolution by treatment arm.

Related articles

Related articles are currently not available for this article.