Favipiravir versus Arbidol for COVID-19: A Randomized Clinical Trial

Abstract

BackgroundNo clinically proven effective antiviral strategy exists for the epidemic Coronavirus Disease 2019 . MethodsWe conducted a prospective, randomized, controlled, open-label multicenter trial involving adult patients with COVID-19. Patients were randomly assigned in a 1:1 ratio to receive conventional therapy plus Umifenovir (Arbidol) (200mg*3/day) or Favipiravir (1600mg*2/first day followed by 600mg*2/day) for 10 days. The primary outcome was clinical recovery rate of Day 7. Latency to relief for pyrexia and cough, the rate of auxiliary oxygen therapy (AOT) or noninvasive mechanical ventilation (NMV) were the secondary outcomes. Safety data were collected for 17 days.

Prioritisation of potential anti-SARS-CoV-2 drug repurposing opportunities based on ability to achieve adequate plasma and target site concentrations derived from their established human pharmacokinetics

“…A recent trial for favipirivir, demonstrated some success with an improvement over arbidol from 56% to 71% (p = 0.02) in patients without risk factors (but not critical cases or patients with hypertension and/or diabetes) [38]. The results of compassionate use of remdesivir in severely ill patients was also recently reported, and if confirmed in ongoing randomized, placebo-controlled trials will serve as a further validation of the other candidates presented here [39].…”

Structure of the RNA-dependent RNA polymerase from COVID-19 virus

“…The efficacy of chain-terminating nucleotide analogs requires viral RdRps to recognize and successfully incorporate the active form of the inhibitors into the growing RNA strand. Sofosbuvir (2'-F-2'-C-methyluridine monophosphate) is a prodrug which targets HCV ns5b and has been approved for the treatment of chronic HCV infection (16). It acts by binding to the catalytic site of HCV ns5b polymerase (12,16).…”

“…Sofosbuvir (2'-F-2'-C-methyluridine monophosphate) is a prodrug which targets HCV ns5b and has been approved for the treatment of chronic HCV infection (16). It acts by binding to the catalytic site of HCV ns5b polymerase (12,16). Given that remdesivir and sofosbuvir are both nucleotide analogs and the structural conservation of the catalytic site between COVID-19 virus nsp12 and HCV ns5b polymerase (13, 16) ( fig.…”

Treatment of SARS-CoV-2: How far have we reached?

“…The results were published on March 20, 2020 which revealed that the 7 day's recovery rate for arbidol group was 55.86% in comparison to 71.43% for favipiravir group (p = 0.0199). Patients with hypertension or diabetes also showed better improvement in case of favipiravir group in comparison to arbidol (15). Currently, three more phase IV clinical trials are planned for arbidol in the treatment of COVID-19.…”

“…Favipiravir was first developed in Japan by Fujifilm and was subjected to another clinical trial on 340 patients in China recently and resulted in very encouraging results as the patients receiving favipiravir with standard care showed cleared viral load in four days as compared to eleven days in patients receiving standard care only (14). Another multicentre, open labeled, randomized trial in China was conducted to compare the efficacy of favipiravir (1,600 mg × 2 on the first day followed by 600 mg × 2 for 9 days) and umifenovir (200 mg × 3 per day for 10 days) and the results revealed a higher recovery rate and better clinical outcomes in the patients treated with favipiravir at day 7 (15). A phase III trial is ongoing in Japan involving 100 patients and is expected to be completed in June.…”