@article{Tate_M-2025_207113,
title = {Clinical effectiveness, safety and viral mutagenicity of oral favipiravir for COVID-19: results from a community-based, open-label, randomised, phase III trial},
author = {Tate, M. and Illingworth, C. and MacGregor, G. and Cunningham, L. and Divers, L. and McCartney, E. and Paterson, L. and Kelly, C. and Shaw, A. and Perkins, J. and Silva, V. and Holland, P. and Dalton, C. and Carmichael, S. and Douglas, E. and Surtees, P. and Scott, J. and Berry, C. and Vattipally, S. and da Silva Filipe, A. and Tong, L. and Gunson, R. and co-investigators, G. and McInnes, I. and Jones, R. and Thomson, E. and Blyth, K.},
month = {jun},
year = {2025},
abstract = {Early community treatment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection may reduce severe coronavirus disease (COVID-19) incidence. We evaluated clinical effectiveness, safety, and SARS-CoV-2 mutagenicity of favipiravir, an oral viral RNA polymerase inhibitor. We performed an open-label, community-based, randomized Phase III trial, recruiting non-hospitalized adults with mild COVID-19 (WHO ordinal severity score [OSS] ≤ 3). Positive cases were invited to web-based self-screening within 24 h using public health data. Exclusion criteria included symptoms for &gt;7 days, pregnancy/breastfeeding, severe renal/liver disease, gout, and licensed antiviral eligibility. Participants were randomized 1:1 to 10 days favipiravir (Day 1: 3,600 mg; days 2-10: 1,600 mg) or no additional treatment. The primary endpoint was worst recorded OSS up to and including Day 15 (intention-to-treat). The target recruitment was 302. Secondary endpoints included adverse event (AE) rate to Day 60, time-to-viral clearance (TTVC), time-to-symptom resolution (TTSR), and SARS-CoV-2 sequencing variant rate (≥5% frequency) at Day 15 (registration ISRCTN: 31062548; EudraCT: 2020-001904-41). A total of 68,788 adults were invited, and 302 (0.4%) were subsequently randomized between December 2020 and July 2022 (favipiravir [n = 152]: standard care [n = 150]). Mean (SD) age was 47.2 (13.2), and 230/302 (76%) were vaccinated. Severe outcomes were infrequent, with no intensive care unit admissions/deaths. There was no difference in the primary endpoint: odds ratio 1.18 (95% confidence interval [CI] 0.63–2.20), TTSR (HR 1.03 [95% CI 0.81–1.31]), or TTVC (HR 1.13 [95% CI 0.65–1.97]). Favipiravir was well tolerated with few AEs but was associated with increased variant frequency, including C-to-U mutations. Community administration of favipiravir for mild COVID-19 was not associated with clinical benefits or safety concerns but was associated with SARS-CoV-2 mutagenicity.},
journal = {Antimicrobial Agents and Chemotherapy},
publisher = {American Society for Microbiology},
url = {https://doi.org/10.1128/aac.00054-25},
}
