TY - JOUR
AU - Tate, Matthew
AU - Illingworth, Christopher J.R.
AU - MacGregor, Gordon
AU - Cunningham, Laura
AU - Divers, Laura
AU - McCartney, Elaine
AU - Paterson, Lucy
AU - Kelly, Caroline
AU - Shaw, Ann
AU - Perkins, Jonathan S.
AU - Silva, Vanessa
AU - Holland, Poppy
AU - Dalton, Carol
AU - Carmichael, Samantha
AU - Douglas, Elizabeth
AU - Surtees, Pamela
AU - Scott, Janet T.
AU - Berry, Colin
AU - Vattipally, Sreenu
AU - da Silva Filipe, Ana
AU - Tong, Lily
AU - Gunson, Rory N.
AU - GETAFIX trial co-investigators
AU - McInnes, Iain B.
AU - Jones, Robert R.
AU - Thomson, Emma C.
AU - Blyth, Kevin G.
PY - 2025
DA - June
TI - Clinical effectiveness, safety and viral mutagenicity of oral favipiravir for COVID-19: results from a community-based, open-label, randomised, phase III trial
JO - Antimicrobial Agents and Chemotherapy
DO - https://doi.org/10.1128/aac.00054-25
AB - 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.
PB - American Society for Microbiology
UR - https://eprints.gla.ac.uk/357376/
KW - Coronavirus (COVID-19)
ER