Favipiravir Versus Arbidol for Clinical Recovery Rate in Moderate and Severe Adult COVID-19 Patients: A Prospective, Multicenter, Open-Label, Randomized Controlled Clinical Trial

Abstract

Background: In addition to supportive therapy, antiviral therapy is an effective treatment for coronavirus disease 2019 (COVID-19).Objective: To compare the efficacy and safety of favipiravir and umifenovir (Arbidol) to treat COVID-19 patients.Methods: We conducted a prospective, randomized, controlled, open-label multicenter trial involving adult patients with COVID-19. Enrolled patients with initial symptoms within 12 days were randomly assigned in a 1:1 ratio to receive conventional therapy plus Arbidol (200 mg*3/day) or favipiravir (1600 mg*2/first day followed by 600 mg*2/day) for 7 days. The primary outcome was the clinical recovery rate at day 7 of drug administration (relief for pyrexia and cough, respiratory frequency ≤24 times/min; oxygen saturation ≥98%). Latency to relief for pyrexia and cough and the rate of auxiliary oxygen therapy (AOT) or noninvasive mechanical ventilation (NMV)/mechanical ventilation (MV) were the secondary outcomes. Safety data were collected for 17 days.Results: A total of 240 enrolled COVID-19 patients underwent randomization; 120 patients were assigned to receive favipiravir (116 assessed), and 120 patients were assigned to receive Arbidol (120 assessed). The clinical recovery rate at day 7 of drug administration did not significantly differ between the favipiravir group (71/116) and Arbidol group (62/120) (p = 0.1396, difference in recovery rate: 0.0954; 95% CI: −0.0305∼0.2213). Favipiravir contributed to relief for both pyrexia (difference: 1.70 days, p < 0.0001) and cough (difference: 1.75 days, p < 0.0001). No difference was observed in the AOT or NMV/MV rate (both p > 0.05). The most frequently observed favipiravir-associated adverse event was increased serum uric acid (16/116, OR: 5.52, p = 0.0014).Conclusion: Among patients with COVID-19, favipiravir, compared to Arbidol, did not significantly improve the clinical recovery rate at day 7. Favipiravir significantly improved the latency to relieve pyrexia and cough. Adverse effects caused by favipiravir are mild and manageable.

Evaluation of risk factors for uric acid elevation in COVID-19 patients treated with favipiravir

“…Thus, favipiravir therapy may induce a dose-dependent increase in uric acid levels. Indeed, in this study, wherein the COVID-19 patients were administered a higher dose of favipiravir than the approved favipiravir regimen for influenza, the incidence rate of uric acid elevation was markedly higher than in some previous studies ( Chen et al, 2021 , Report on the Deliberation Results 2014 ). Therefore, we consider that the dosage of favipiravir is closely related to uric acid elevation.…”

“…In addition, the median onset time of uric acid elevation was 4.5 days. Previously, in a randomized control trial among COVID-19 patients to compare the efficacy and safety of favipiravir and arbidol, the incidence of uric acid elevation was significantly higher in the favipiravir group (13.8%) than in the arbidol group (2.5%) ( Chen et al, 2021 ). In an interim report of a multicenter observational study of favipiravir in COVID-19 patients in Japan, 17.6% (524/2970) of the patients showed hyperuricemia or uric acid elevation with favipiravir therapy, and 0.30% (9/2970) presented with gout ( Favipiravir Observational Study Group, Fujita Health University 2020 ).…”

“…The incorporation of favipiravir-RTP in the nascent viral RNA could result either in lethal mutagenesis by ambiguous base-pairing or in chain termination. Due to its activity against RNA viruses, the efficacy of favipiravir against several RNA viruses including SARS-CoV-2, Influenza A virus subtype H1N1, Ebola virus, etc., has been tested ( Holshue et al, 2020 , Chen et al, 2021 , Sangawa et al, 2013 , Tarbet et al, 2014 , Kerber et al, 2019 ).…”

Study of Clinical and Pathogenetic Effects of Anti-Viral Drug Based on Favipiravir in Comorbid Patients With Covid-19 at the Outpatient Stage of Treatment

“…При проведении Chen С. с соавт. сравнительного анализа эффективности фавипиравира и арбидола для лечения COVID-19 было установлено, что при среднетяжелом течении заболевания у пациентов с сопутствующими АГ и/или сахарным диабетом временной отрезок до нормализации температуры тела и исчезновение кашля был достоверно короче в группе, применяющей фавипиравир, по сравнению с группой, использующей арбидол (р<0,001) [7].…”

“…По данным анализа карт амбулаторных пациен- [5,7,10,11]. Анализ фармако-экономического эффекта повышения частоты раннего назначения препарата «Аре-пливир®» в Республике Мордовия в период с 1 октября 2021 по 1 ноября 2021 с учетом проводимой благотворительной акции (16 672 упаковки препарата были распределены среди 8 336 заболевших пациентов) выявил снижение уровня госпитализации в регионе за 1 месяц на 1757 человек при сопоставлении с сентябрем 2021.…”