A randomised controlled trial of early intervention with oral favipiravir in patients hospitalised with COVID-19 (PIONEER Trial)

Abstract

Background: Oral anti-viral therapies are licensed worldwide in COVID-19 but indications and efficacy rates vary.

Aims and Objectives: To evaluate the safety and efficacy of oral favipiravir in patients hospitalised with COVID-19.

Methods: We conducted a multi-centre, open-label, randomised controlled trial of oral favipiravir in patients newly hospitalised with COVID-19, in five centres worldwide. 500 participants were randomised 1:1 to receive oral favipiravir (1800 mg twice daily (BD) for one-day; 800 mg BD for nine-days) plus standard care (SC), or SC alone. NCT: 04373733.

Results: Recruitment was performed between May 2020 and May 2021, with 251 patients randomised to favipiravir and 249 to SC. There was no difference in time to recovery in all patients (HR 1·06; 95% CI 0·89-1·27; n=499; p=0.52). A faster rate of recovery was observed in patients receiving favipiravir under the age of 60 years (HR 1·35; 95% CI 1·06-1·72; n=247, p=0·01). A 66 % improvement in mechanical ventilation free survival was evident in patients under 60-years of age (HR 0·34; 95% CI 0·13-0·85; n=247, p=0·02). A non-significant 26 % reduction in mortality was observed in patients receiving favipiravir (favipiravir: 26; SC: 34; p=0·24). No significant differences were observed in serious adverse events (SAE) between arms (favipiravir: 36 in 27 patients; SC: 33 in 27 patients).

Conclusions: Orally administered favipiravir has a beneficial effect on recovery, and mechanical ventilation free-survival in patients under 60-years of age, hospitalised with COVID-19. Wider evaluation of anti-viral medications and their potential treatment combinations is warranted in patients with COVID-19.