TY - JOUR
T1 - Favipiravir for Treatment of Outpatients With Asymptomatic or Uncomplicated Coronavirus Disease 2019
T2 - A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Trial
AU - Holubar, Marisa
AU - Subramanian, Aruna
AU - Purington, Natasha
AU - Hedlin, Haley
AU - Bunning, Bryan
AU - Walter, Katharine S.
AU - Bonilla, Hector
AU - Boumis, Athanasia
AU - Chen, Michael
AU - Clinton, Kimberly
AU - Dewhurst, Liisa
AU - Epstein, Carol
AU - Jagannathan, Prasanna
AU - Kaszynski, Richard H.
AU - Panu, Lori
AU - Parsonnet, Julie
AU - Ponder, Elizabeth L.
AU - Quintero, Orlando
AU - Sefton, Elizabeth
AU - Singh, Upinder
AU - Soberanis, Luke
AU - Truong, Henry
AU - Andrews, Jason R.
AU - Desai, Manisha
AU - Khosla, Chaitan
AU - Maldonado, Yvonne
N1 - Publisher Copyright: © The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.
PY - 2022/11/30
Y1 - 2022/11/30
N2 - BACKGROUND: Favipiravir, an oral, RNA-dependent RNA polymerase inhibitor, has in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite limited data, favipiravir is administered to patients with coronavirus disease 2019 (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-CoV-2 reverse-transcription polymerase chain reaction assay (RT-PCR) within 72 hours of enrollment. Participants were randomized to receive placebo or favipiravir (1800 mg twice daily [BID] day 1, 800 mg 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 amplicon-based sequencing, we assessed favipiravir's impact on mutagenesis. RESULTS: We randomized 149 participants with 116 included in the mITT cohort. The participants' mean age was 43 years (standard deviation, 12.5 years) and 57 (49%) were women. We found no difference in time to shedding cessation overall (hazard ratio [HR], 0.76 favoring placebo [95% confidence interval {CI}, .48-1.20]) or in subgroups (age, sex, high-risk comorbidities, seropositivity, or symptom duration at enrollment). We detected no difference in time to symptom resolution (initial: HR, 0.84 [95% CI, .54-1.29]; sustained: HR, 0.87 [95% CI, .52-1.45]) and no difference in transition mutation accumulation in the viral genome during treatment. CONCLUSIONS: Our data do not support favipiravir at commonly used doses in outpatients with uncomplicated COVID-19. Further research is needed to ascertain if higher favipiravir doses are effective and safe for patients with COVID-19. CLINICAL TRIALS REGISTRATION: NCT04346628.
AB - BACKGROUND: Favipiravir, an oral, RNA-dependent RNA polymerase inhibitor, has in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite limited data, favipiravir is administered to patients with coronavirus disease 2019 (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-CoV-2 reverse-transcription polymerase chain reaction assay (RT-PCR) within 72 hours of enrollment. Participants were randomized to receive placebo or favipiravir (1800 mg twice daily [BID] day 1, 800 mg 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 amplicon-based sequencing, we assessed favipiravir's impact on mutagenesis. RESULTS: We randomized 149 participants with 116 included in the mITT cohort. The participants' mean age was 43 years (standard deviation, 12.5 years) and 57 (49%) were women. We found no difference in time to shedding cessation overall (hazard ratio [HR], 0.76 favoring placebo [95% confidence interval {CI}, .48-1.20]) or in subgroups (age, sex, high-risk comorbidities, seropositivity, or symptom duration at enrollment). We detected no difference in time to symptom resolution (initial: HR, 0.84 [95% CI, .54-1.29]; sustained: HR, 0.87 [95% CI, .52-1.45]) and no difference in transition mutation accumulation in the viral genome during treatment. CONCLUSIONS: Our data do not support favipiravir at commonly used doses in outpatients with uncomplicated COVID-19. Further research is needed to ascertain if higher favipiravir doses are effective and safe for patients with COVID-19. CLINICAL TRIALS REGISTRATION: NCT04346628.
KW - COVID-19
KW - SARS-CoV-2
KW - clinical trial
KW - favipiravir
UR - http://www.scopus.com/inward/record.url?scp=85143180521&partnerID=8YFLogxK
U2 - https://doi.org/10.1093/cid/ciac312
DO - https://doi.org/10.1093/cid/ciac312
M3 - Article
C2 - 35446944
SN - 1058-4838
VL - 75
SP - 1883
EP - 1892
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 11
ER -