tetano
Editor, Senior Moderator
Antimicrob Agents Chemother
. 2025 Jun 24:e0005425.
doi: 10.1128/aac.00054-25. Online ahead of print. Clinical effectiveness, safety, and viral mutagenicity of oral favipiravir for COVID-19: results from a community-based, open-label, randomized Phase III trial
Matthew Tate[SUP] 1 2 [/SUP], Christopher J R Illingworth[SUP] 3 [/SUP], Gordon MacGregor[SUP] 1 [/SUP], Laura Cunningham[SUP] 4 [/SUP], Laura Divers[SUP] 4 [/SUP], Elaine McCartney[SUP] 4 [/SUP], Lucy Paterson[SUP] 4 [/SUP], Caroline Kelly[SUP] 4 [/SUP], Ann Shaw[SUP] 4 [/SUP], Jonathan S Perkins[SUP] 5 [/SUP], Vanessa Silva[SUP] 5 [/SUP], Poppy Holland[SUP] 5 [/SUP], Carol Dalton[SUP] 5 [/SUP], Samantha Carmichael[SUP] 5 [/SUP], Elizabeth Douglas[SUP] 5 [/SUP], Pamela Surtees[SUP] 5 [/SUP], Janet T Scott[SUP] 3 [/SUP], Colin Berry[SUP] 6 7 [/SUP], Sreenu Vattipally[SUP] 3 [/SUP], Ana Da Silva Filipe[SUP] 3 [/SUP], Lily Tong[SUP] 3 [/SUP], Rory Gunson[SUP] 8 [/SUP]; GETAFIX trial co-investigators; Iain B McInnes[SUP] 9 [/SUP], Robert Jones[SUP] 2 4 [/SUP], Emma Thomson[SUP] 3 9 [/SUP], Kevin G Blyth[SUP] 1 2 10 [/SUP]
Collaborators, Affiliations
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 >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.CLINICAL TRIALSThis study is registered with ISRCTN as 31062548 and with EU-CTR as 2020-001904-41.
Keywords: COVID-19; antiviral agents; randomized controlled trial.
. 2025 Jun 24:e0005425.
doi: 10.1128/aac.00054-25. Online ahead of print. Clinical effectiveness, safety, and viral mutagenicity of oral favipiravir for COVID-19: results from a community-based, open-label, randomized Phase III trial
Matthew Tate[SUP] 1 2 [/SUP], Christopher J R Illingworth[SUP] 3 [/SUP], Gordon MacGregor[SUP] 1 [/SUP], Laura Cunningham[SUP] 4 [/SUP], Laura Divers[SUP] 4 [/SUP], Elaine McCartney[SUP] 4 [/SUP], Lucy Paterson[SUP] 4 [/SUP], Caroline Kelly[SUP] 4 [/SUP], Ann Shaw[SUP] 4 [/SUP], Jonathan S Perkins[SUP] 5 [/SUP], Vanessa Silva[SUP] 5 [/SUP], Poppy Holland[SUP] 5 [/SUP], Carol Dalton[SUP] 5 [/SUP], Samantha Carmichael[SUP] 5 [/SUP], Elizabeth Douglas[SUP] 5 [/SUP], Pamela Surtees[SUP] 5 [/SUP], Janet T Scott[SUP] 3 [/SUP], Colin Berry[SUP] 6 7 [/SUP], Sreenu Vattipally[SUP] 3 [/SUP], Ana Da Silva Filipe[SUP] 3 [/SUP], Lily Tong[SUP] 3 [/SUP], Rory Gunson[SUP] 8 [/SUP]; GETAFIX trial co-investigators; Iain B McInnes[SUP] 9 [/SUP], Robert Jones[SUP] 2 4 [/SUP], Emma Thomson[SUP] 3 9 [/SUP], Kevin G Blyth[SUP] 1 2 10 [/SUP]
Collaborators, Affiliations
- PMID: 40552814
- DOI: 10.1128/aac.00054-25
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 >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.CLINICAL TRIALSThis study is registered with ISRCTN as 31062548 and with EU-CTR as 2020-001904-41.
Keywords: COVID-19; antiviral agents; randomized controlled trial.