TY - JOUR
T1 - Favipiravir in Patients with Early Mild-to-moderate Coronavirus Disease 2019 (COVID-19)
T2 - A Randomized Controlled Trial
AU - Golan, Yoav
AU - Campos, Jesus Abraham Simon
AU - Woolson, Rob
AU - Cilla, Donald
AU - Hanabergh, Rodolfo
AU - Gonzales-Rojas, Yaneicy
AU - Lopez, Reynaldo
AU - Finberg, Robert
AU - Balboni, Armand
N1 - Funding Information:
Potential Conflicts of Interest. Y. G. is an employee of Appili Therapeutics in the capacity of Chief Medical Officer. Speaker: Pfizer, Sanofi, AbbVie, Paratek, Shionogi, Merk. Consultant/advisor: Pfizer, Seres, Sanofi. Stock options: Appili Therapeutics, Inc. Grants from NIH, CO-PI, niclosamide in COVID-19. J. A. S. C. is Advisor and speaker: Pfizer, Astra Zeneca, and Regeneron (paid to author). Served as site PI in this clinical trial and reimbursed for subject enrollment. Consulting fees include advisory board Astrazeneca and advisory board Pfizer (paid to author). R. W. is an employee of Rho, Inc, Durham, North Carolina, USA. Served as the study's statistician. D. C. is an employee of Appili Therapeutics in the capacity of Chief Development Officer. Stock options: Appili Therapeutics, Inc. R. H. served as site PI in this clinical trial and reimbursed for subject enrollment. Y. G.-R. served as site PI in this clinical trial and reimbursed for subject enrollment. R. L. served as site PI in this clinical trial and reimbursed for subject enrollment. R. F. (deceased) served as site PI in this clinical trial and reimbursed for subject enrollment. A. B. is an employee of Appili Therapeutics, Inc, in the capacity of Chief Executive Officer. Stock options: Appili Therapeutics, Inc; includes grant or contracts from US DoD – Research Grants unrelated to COVID-19/Favipiravir. All other authors report no potential conflicts.
Publisher Copyright:
© 2022 The Author(s). Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved.
PY - 2023/2/1
Y1 - 2023/2/1
N2 - Background: Despite vaccination, many remain vulnerable to coronavirus disease 2019 (COVID-19) and its complications. Oral antivirals to prevent COVID-19 progression are vital. Based on perceived potency and clinical efficacy, favipiravir is widely used to treat COVID-19. Evidence from large randomized controlled trials (RCT) is lacking. Methods: In this multicenter double-blinded placebo-controlled RCT, adults with early mild-to-moderate COVID-19 were 1:1 randomized to favipiravir or placebo. The study evaluated time to sustained clinical recovery (TT-SCR), COVID-19 progression, and cessation of viral shedding. Results: Of 1187 analyzed patients across 40 centers, 83.3% were Hispanic, 89.0% unvaccinated, 70.3% severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seronegative, and 77.8% had risk factors for COVID-19 progression. The median time from symptom presentation and from positive test to randomization was 3 and 2 days, respectively. There was no difference in TT-SCR (median of 7 days for both groups; P =. 80), COVID-19 progression [11 patients each (1.9% vs 1.8%); P =. 96], time to undetectable virus (median = 6 days, 95% confidence interval [CI] [6-8] vs 7 days, 95% CI [6-9]), or in undetectable virus by end of therapy (73.4% vs 72.3%; P =. 94). Outcomes were consistent across the analyzed sub-groups. Adverse events were observed in 13.8% and 14.8% of favipiravir-treated and placebo-treated subjects, respectively. Uric acid elevation was more frequent among favipiravir-treated subjects (19.9% vs 2.8%). Conclusions: Favipiravir was well tolerated but lacked efficacy in TT-SCR, progression to severe COVID-19, or cessation of viral shedding and should not be used to treat patients with COVID-19.
AB - Background: Despite vaccination, many remain vulnerable to coronavirus disease 2019 (COVID-19) and its complications. Oral antivirals to prevent COVID-19 progression are vital. Based on perceived potency and clinical efficacy, favipiravir is widely used to treat COVID-19. Evidence from large randomized controlled trials (RCT) is lacking. Methods: In this multicenter double-blinded placebo-controlled RCT, adults with early mild-to-moderate COVID-19 were 1:1 randomized to favipiravir or placebo. The study evaluated time to sustained clinical recovery (TT-SCR), COVID-19 progression, and cessation of viral shedding. Results: Of 1187 analyzed patients across 40 centers, 83.3% were Hispanic, 89.0% unvaccinated, 70.3% severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seronegative, and 77.8% had risk factors for COVID-19 progression. The median time from symptom presentation and from positive test to randomization was 3 and 2 days, respectively. There was no difference in TT-SCR (median of 7 days for both groups; P =. 80), COVID-19 progression [11 patients each (1.9% vs 1.8%); P =. 96], time to undetectable virus (median = 6 days, 95% confidence interval [CI] [6-8] vs 7 days, 95% CI [6-9]), or in undetectable virus by end of therapy (73.4% vs 72.3%; P =. 94). Outcomes were consistent across the analyzed sub-groups. Adverse events were observed in 13.8% and 14.8% of favipiravir-treated and placebo-treated subjects, respectively. Uric acid elevation was more frequent among favipiravir-treated subjects (19.9% vs 2.8%). Conclusions: Favipiravir was well tolerated but lacked efficacy in TT-SCR, progression to severe COVID-19, or cessation of viral shedding and should not be used to treat patients with COVID-19.
KW - COVID-19
KW - antiviral
KW - favipiravir
KW - progression
KW - treatment
UR - http://www.scopus.com/inward/record.url?scp=85141270550&partnerID=8YFLogxK
U2 - 10.1093/cid/ciac712
DO - 10.1093/cid/ciac712
M3 - Article
C2 - 36065065
AN - SCOPUS:85141270550
SN - 1058-4838
VL - 76
SP - E10-E17
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 3
ER -
