Efficacy and safety of favipiravir in a complex therapy of mild to moderate COVID-19
AbstractAim of the study - to assess the efficacy and safety of favipiravir for treatment of mild to moderate coronavirus disease (COVID-19).
Material and methods. An open-labeled, randomized, active-controlled multicenter trial of favipiravir in out- and hospitalized patients with mild to moderate COVID-19 was conducted. Eligible patients were aged 18-60 years and had laboratory confirmed by PCR test infection of SARS-CoV-2. Patients were randomly assigned in a 2:1 ratio to receive either favipiravir (1800 mg BID on day 1, followed by 800 mg BID for 9 days), or standard of care (SOC) treatment (umifenovir + intranasal interferon alpha-2b, or hydroxychloroquine for up to 10 days). In needed, patients received concomitant symptomatic medication. The co-primary outcomes were the time to clinical improvement and the time to viral clearance.
Results and discussion. It was found that the median time to clinical improvement was 6.0 [interquartile range (IQR) 4.0; 9.3] days in favipiravir group and 10.0 (IQR 5.0; 21.0) days in SOC group; the median difference was 4 days [hazard ratio (HR) 1.63; 95% confidence interval (CI) 1.14-2.34, p=0.007]. The rate of clinical improvement in the favipiravir group on day 7 was 1.5-fold higher compared to SOC: 52.7% vs 35.7% [risk ratio (RR) 1.50; 95% CI 1.02-2.22; p=0.020]. Despite an absence of statistically significant difference between the median time to viral elimination, the rates of viral elimination on day 3 and day 5 were significantly higher in favipiravir group: on the day 3 viral elimination was observed for in 71.4% of patients, who received favipiravir vs 57.1% in SOC group (RR 1.27; 95% CI 0.99-1.64; p=0.030), on the day 5 81.2 vs 67.9%, respectively (RR 1.22; 95% CI 1.00-1.48; р=0.022).
Favipiravir was well tolerated: most of the adverse events (AE) were mild. The most common AEs were asymptomatic hyperuricemia, transient elevation of ALT & AST, and gastrointestinal disorders (diarrhea, nausea, abdominal pain).
This study confirmed the superiority of favipiravir vs standard ethiotropic therapy in treatment of patients with mild to moderate COVID-19.
Keywords:COVID-19, SARS-CoV-2, coronavirus pneumonia, coronavirus infection, favipiravir
Funding. The study was carried out with the sponsorship of the R-Pharm Group of Companies.
Conflict of interests. Authors declare no conflict of interests
Contribution. Study concept and design - Brook Yu.F., Shestakova I.V., Krasavina E.N., Samsonov M.Yu., Nikolskaya M.V., Razzhivina V.A., Vafin A.Yu.; clinical part conduction - Ruzhentsova T.A., Chukhlyaev P.V., Khavkina D.A., Garbuzov A.A., Ploskireva A.A., Oseshnyuk R.A., Soluyanova T.N., Shestakova I.V., Vafin A.Yu., Dmitrikova E.P., Mustafaev D.M., Domostroeva T.N., Otpuschennikova M.V., Pokrovsky K.A., Rusanova M.G., Bystritsky D.A., Markova T.N., Kaplun E.A., Petina D.V, Kostina N.E., Lesina V.S., Shcherbak S.G., Agafina A.S., Razzhivina V.A.; CT data assessment - Bronov O.Yu., Shultz E.I.; data analysis - Ruzhentsova T.A., Zinchenko A.V., Nikolskaya M.V., Filon O.V.; manuscript writing: Ruzhentsova T.A., Krasavina E.N., Zinchenko A.V., Nikolskaya M.V., Filon O.V.
For citation: Ruzhentsova T.A., Chukhlyaev P.V., Khavkina D.A., Garbuzov A.A., Ploskireva A.A., Oseshnyuk R.A., Soluyanova T.N., Shestakova I.V., Vafin A.Yu., Dmitrikova E.P., Mustafaev D.M., Domostroeva T.N., Otpuschennikova M.V., Pokrovsky K.A., Rusanova M.G., Bystritsky D.A., Markova T.N., Kaplun E.A., Petina D.V., Kostina N.E., Lesina V.S., Shcherbak S.G., Agafina A.S., Brook Yu.F.,Bronov O.Yu., Shultz E.I., Krasavina E.N., Samsonov M.Yu., Zinchenko A.V., Nikolskaya M.V., Razzhivina V.A., Filon O.V. Efficacy and safety of favipiravir in a complex therapy of mild to moderate COVID-19. Infektsionnye bolezni: novosti, mneniya, obuchenie [Infectious Diseases: News, Opinions, Training]. 2020; 9 (4): 26-38. DOI: https://doi.org/10.33029/2305-3496-2020-9-4-26-38 (in Russian)
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