Various Combinations of Favipiravir, Lopinavir-Ritonavir, Darunavir-Ritonavir, High-Dose Oseltamivir, and Hydroxychloroquine for the Treatment of COVID-19: A Randomized Controlled Trial (FIGHT-COVID-19 Study)

Atipornwanich et al., SSRN Electronic Journal, doi:10.2139/ssrn.3936499, FIGHT-COVID-19, NCT04303299

Oct 2021

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RCT 200 moderate/severe patients in Thailand, showing significantly lower progression with favipiravir vs. oseltamivir. NCT04303299 (history).

Potential risks of favipiravir include the creation of dangerous variants, and mutagenicity, carcinogenicity, teratogenicity, and embryotoxicity1-5.

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Study covers favipiravir and HCQ.

risk of death, 23.1% lower, RR 0.77, p = 0.66, treatment 10 of 100 (10.0%), control 13 of 100 (13.0%), NNT 33, favipiravir arms vs. oseltamivir arms.

risk of progression, 60.0% lower, RR 0.40, p = 0.009, treatment 10 of 100 (10.0%), control 25 of 100 (25.0%), NNT 6.7, favipiravir arms vs. oseltamivir arms.

time to viral-, 8.7% lower, relative time 0.91, p = 0.43, treatment mean 9.5 (±5.0) n=50, control mean 10.4 (±6.3) n=50, HCQ arms, primary outcome.

time to viral-, 8.9% lower, relative time 0.91, p = 0.34, treatment mean 10.2 (±4.6) n=50, control mean 11.2 (±5.7) n=50, non-HCQ arms, primary outcome.

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1. Zhirnov et al., Favipiravir: the hidden threat of mutagenic action, Journal of microbiology, epidemiology and immunobiology, doi:10.36233/0372-9311-114.elpub.ru, doi.org.

2. Waters et al., Human genetic risk of treatment with antiviral nucleoside analog drugs that induce lethal mutagenesis: the special case of molnupiravir, Environmental and Molecular Mutagenesis, doi:10.1002/em.22471.wiley.com, doi.org.

3. Hadj Hassine et al., Lethal Mutagenesis of RNA Viruses and Approved Drugs with Antiviral Mutagenic Activity, Viruses, doi:10.3390/v14040841.mdpi.com, doi.org.

4. Shum, C., An investigational study into the drug-associated mutational signature in SARS-CoV-2 viruses, The University of Hong Kong, PhD Thesis, hub.hku.hk/handle/10722/344396.hku.hk.

5. Shiraki et al., Convenient screening of the reproductive toxicity of favipiravir and antiviral drugs in Caenorhabditis elegans, Heliyon, doi:10.1016/j.heliyon.2024.e35331.sciencedirect.com, doi.org.

Atipornwanich et al., 5 Oct 2021, Randomized Controlled Trial, Thailand, peer-reviewed, 16 authors, study period 19 August, 2020 - 28 August, 2021, this trial compares with another treatment - results may be better when compared to placebo, this trial uses multiple treatments in the treatment arm (combined with lopinavir/ritonavir or duranivir/ritonavir/HCQ) - results of individual treatments may vary, trial NCT04303299 (history) (FIGHT-COVID-19).

This Paper Favipiravir All

M.D Kriangsak Atipornwanich, Associate Professor Subsai Kongsaengdao, M.D Piyathida Harnsomburana, M.D Rienthong Nanna, M.D Chatchawan Chtuparisute, M.D Piamlarp Saengsayan, M.D Kittima Bangpattanasiri, M.D Weerawat Manosuthi, M.D Narumol Sawanpanyalert, M.D Attasit Srisubat, M.D Somchai Thanasithichai, M.D Benchalak Maneeton, M.D Narong Maneeton, Chuthamanee Suthisisang, PhD B Pharm, Jaturong Pratuangdejkul, M.D Somsak Akksilp, Professor Dusit Sujurarat, Hospital Rajavithi, Bangkok Bangkok, Thailand

Various combinations of Favipiravir, Lopinavir-Ritonavir, Darunavir-Ritonavir, high-dose Oseltamivir, and Hydroxychloroquine for the treatment of Covid-19: A randomized controlled trial. (FIGHT-COVID-19 Study)

References

Hata, Koseki, Yamaguchi, Limited inhibitory effects of Oseltamivir and zanamivir on human sialidases, Antimicrob Agents Chemother, doi:10.1128/AAC.00344-08

Hung, Lung, Tso, Triple combination of interferon beta-1b, lopinavirritonavir, and ribavirin in the treatment of patients admitted to hospital with Covid -19: an open-label, randomised, phase 2 trial, Lancet, doi:10.1016/S0140-6736(20)31042-4

Kriangsak, Akksilp, Sawanpanyalert, Srisubat, Thanasithichai et al., Various Combination of Antiviral Treatment of Covid -19 Pneumonia

Shinkai, Tsushima, Tanaka, A Randomized, Phase III Clinical Trial, Infect Dis Ther, doi:10.1007/s40121-021-00517-4

Wang, Zhang, Du, Remdesivir in adults with severe Covid -19: a randomised, doubleblind, placebo-controlled, multicentre trial [published correction appears in, Lancet

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Late treatment
is less effective

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