MD, MS Yoav Golan, Jesus Abraham, MD, Kohler Simon Campos, Milstein Research, S A De, MD Rodolfo Hanabergh, MD, Verus Yaneicy Gonzales-Rojas, MD Reynaldo Lopez, M.D. (deceased Robert Finberg, MD Armand Balboni
Background: Despite vaccination, many remain vulnerable to COVID-19 and its complications. Oral antivirals to prevent COVID-19 progression are vital. Based upon 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-tomoderate 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% 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 three and two days, respectively. There was no difference in TT-SCR (median of 7 days for both groups; p=0.80), COVID-19 progression [11 patients each (1.9% vs. 1.8%); p=0.96], time to undetectable virus [median=6 days, 95% CI (6-8) vs. 7 days, 95% CI (6-9)], or in undetectable virus by end of therapy (73.4% vs. 72.3%; p=0.94). 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. (Supported by Appili Therapeutics
Jesus Abraham Simon Campos, MD: 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).
Rob
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'abstract': '<jats:title>Abstract</jats:title>\n'
' <jats:sec>\n'
' <jats:title>Background</jats:title>\n'
' <jats:p>Despite vaccination, many remain vulnerable to COVID-19 and its '
'complications. Oral antivirals to prevent COVID-19 progression are vital. Based upon '
'perceived potency and clinical efficacy, favipiravir is widely used to treat COVID-19. '
'Evidence from large randomized controlled trials (RCT) is lacking.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Methods</jats:title>\n'
' <jats:p>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.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Results</jats:title>\n'
' <jats:p>Of 1187 analyzed patients across 40 centers, 83.3% were Hispanic, '
'89.0% unvaccinated, 70.3% 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 three and two days, respectively. There was no difference in TT-SCR (median '
'of 7 days for both groups; p\u2009=\u20090.80), COVID-19 progression [11 patients each (1.9% '
'vs. 1.8%); p\u2009=\u20090.96], time to undetectable virus [median\u2009=\u20096 days, 95% CI '
'(6-8) vs. 7 days, 95% CI (6-9)], or in undetectable virus by end of therapy (73.4% vs. 72.3%; '
'p\u2009=\u20090.94). 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%).</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Conclusions</jats:title>\n'
' <jats:p>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.</jats:p>\n'
' </jats:sec>',
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