Efficacy and safety of favipiravir plus interferon-beta versus lopinavir/ritonavir plus interferon-beta in moderately ill patients with COVID-19: A randomized clinical trial
et al., Journal of Medical Virology, doi:10.1002/jmv.27724, IRCT20200506047323N3, Mar 2022
RCT comparing favipiravir and lopinavir/ritonavir, showing no significant differences. All patients received interferon-beta. Favipiravir 1600mg bid for the first day and 600mg bid for the following 4 days.
Potential risks of favipiravir include kidney injury1-3, liver injury2-4, and mutagenicity, carcinogenicity, teratogenicity, embryotoxicity, and the creation of dangerous variants5-11.
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risk of death, 67.7% lower, RR 0.32, p = 0.15, treatment 2 of 32 (6.2%), control 6 of 31 (19.4%), NNT 7.6, day 14.
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risk of death, 3.1% lower, RR 0.97, p = 1.00, treatment 1 of 32 (3.1%), control 1 of 31 (3.2%), NNT 992, day 7.
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risk of ICU admission, 35.4% lower, RR 0.65, p = 0.51, treatment 4 of 32 (12.5%), control 6 of 31 (19.4%), NNT 15, day 14.
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hospitalization time, 25.0% lower, relative time 0.75, p = 0.14, treatment 32, control 31.
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risk of no viral clearance, 18.0% lower, RR 0.82, p = 0.24, treatment 22 of 32 (68.8%), control 26 of 31 (83.9%), NNT 6.6, day 7.
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| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
1.
Abdulaziz et al., Clinical Features and Prognosis of Acute Kidney Injury in Hospital-Admitted Patients with COVID-19 in Egypt: A Single-Center Experience, Mansoura Medical Journal, doi:10.58775/2735-3990.1433.
2.
Ülger et al., Experimental evaluation of favipiravir (T-705)-induced liver and kidney toxicity in rats, Food and Chemical Toxicology, doi:10.1016/j.fct.2025.115472.
3.
El-Fetouh et al., Experimental Studies on Some Drugs Used in Covid-19 Treatment (Favipiravir and Dexamethasone) in Albino Rats, Journal of Advanced Veterinary Research, 13:10, www.advetresearch.com/index.php/AVR/article/view/1635.
4.
Almutairi et al., Liver Injury in Favipiravir-Treated COVID-19 Patients: Retrospective Single-Center Cohort Study, Tropical Medicine and Infectious Disease, doi:10.3390/tropicalmed8020129.
5.
Zhirnov et al., Favipiravir: the hidden threat of mutagenic action, Journal of microbiology, epidemiology and immunobiology, doi:10.36233/0372-9311-114.
6.
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.
7.
Hadj Hassine et al., Lethal Mutagenesis of RNA Viruses and Approved Drugs with Antiviral Mutagenic Activity, Viruses, doi:10.3390/v14040841.
8.
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.
9.
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.
Hassaniazad et al., 24 Mar 2022, Randomized Controlled Trial, Iran, peer-reviewed, mean age 53.8, 7 authors, this trial compares with another treatment - results may be better when compared to placebo, trial IRCT20200506047323N3.
Contact: m.fathalipour@yahoo.com.
Efficacy and safety of favipiravir plus interferon‐beta versus lopinavir/ritonavir plus interferon‐beta in moderately ill patients with COVID‐19: A randomized clinical trial
Journal of Medical Virology, doi:10.1002/jmv.27724
Favipiravir (FVP), lopinavir/ritonavir (LPV/RTV), and interferon-beta (INF-beta) are considered as potential treatments for COVID-19. We examined the efficacy and safety of FVP and INF-beta compared to LPV/RTV and INF-beta combinations for the treatment of SARS-CoV-2. It was a single-center randomized clinical trial. Eligible patients were randomized to receive FVP plus INF-beta versus LPV/RTV plus INF-beta. The primary endpoint was the viral clearance after seven days of randomization. ICU admission, length of stay (LOS) in hospital, in-hospital mortality, and the incidence of adverse events were also measured. This trial was registered on the Iranian Registry of Clinical Trials (IRCT20200506047323N3). Patients were randomly allocated to the FVP (n = 33) and LPV/RTV (n = 33) groups. The viral clearance on Day seven was not significantly different between the FVP (31.1%) and the LPV/RTV groups (16.1%). The rate of ICU admission and likewise the in-hospital mortality in the FVP group (12.5% and 6.3%, respectively) were similar to the LPV/RTV groups (19.4% and 19.4%, respectively). The median LOS in the hospital was also not different (6.8 days [interquartile range; IQR = 5.0-11.0] in the FVP and (8.0 days [IQR = 5.5-12.5]) in LPV/RTV groups (p = 0.140). Adverse events were observed in 25.0% of FVP and 32.3% of LPV/RTV groups. The combination therapy with FVP did not exert a higher efficacy compared to the combination regimen of LPV/RTV. However, both treatment regimens demonstrated a mild profile of adverse events.
ACKNOWLEDGMENTS The authors appreciably thank the trial patients and their families, whose help and participation made this study possible. This study was financially supported by Hormozgan University of Medical Sciences (Grant no: 990233).
CONFLICTS OF INTEREST The authors declare no conflicts of interest.
SUPPORTING INFORMATION Additional supporting information may be found in the online version of the article at the publisher's website.
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