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Favipiravir in the Treatment of Outpatient COVID-19: A Multicenter, Randomized, Triple-Blind, Placebo-Controlled Clinical Trial

Vaezi et al., Advances in Respiratory Medicine, doi:10.3390/arm91010004, IRCT20171219037964N3
Jan 2023  
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Hospitalization -105% Improvement Relative Risk Favipiravir  Vaezi et al.  EARLY TREATMENT  DB RCT Is early treatment with favipiravir beneficial for COVID-19? Double-blind RCT 77 patients in Iran (December 2020 - March 2021) Higher hospitalization with favipiravir (not stat. sig., p=0.43) c19early.org Vaezi et al., Advances in Respiratory .., Jan 2023 Favorsfavipiravir Favorscontrol 0 0.5 1 1.5 2+
RCT 77 outpatients in Iran, showing increased hospitalization with treatment, without statistical significance. Favipiravir 1600mg daily for five days. 21% of favipiravir patients did not complete treatment.
Potential risks of favipiravir include the creation of dangerous variants, and mutagenicity, carcinogenicity, teratogenicity, and embryotoxicity1-5.
risk of hospitalization, 105.3% higher, RR 2.05, p = 0.43, treatment 4 of 38 (10.5%), control 2 of 39 (5.1%), day 28.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Vaezi et al., 28 Jan 2023, Double Blind Randomized Controlled Trial, placebo-controlled, Iran, peer-reviewed, 6 authors, study period 5 December, 2020 - 31 March, 2021, trial IRCT20171219037964N3. Contact: salahimehrdad@yahoo.com (corresponding author).
This PaperFavipiravirAll
Favipiravir in the Treatment of Outpatient COVID-19: A Multicenter, Randomized, Triple-Blind, Placebo-Controlled Clinical Trial
Atefeh Vaezi, Mehrzad Salmasi, Forogh Soltaninejad, Mehrdad Salahi, Shaghayegh Haghjooy Javanmard, Babak Amra
Advances in Respiratory Medicine, doi:10.3390/arm91010004
What are the main findings? • Favipiravir, an RNA-dependent RNA polymerase inhibitor, shows no benefit in preventing the hospitalization of mild to moderate COVID-19 patients. What is the implication of the main finding? • Our results may inform decisions on the exclusion of Favipiravir from mild to moderate COVID-19 treatment guidelines.
Informed Consent Statement: Patients were informed about the study protocol and objectives and were asked to sign an informed consent before participation. All data were managed, analyzed, and reported anonymously. Medications were provided by the research team and imposed no costs on patients. Conflicts of Interest: The authors declare that they have no conflict of interest.
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Worldometer, COVID-19 Pandemic
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Methods: This study was a triple-blind ' 'randomized controlled trial conducted between 5 December 2020 and 31 March 2021 in three ' 'outpatient centers in Isfahan, Iran. Patients in the intervention group received Favipiravir ' '1600 mg daily for five days, and the control group received a placebo. Our primary outcome ' 'was the proportion of hospitalized participants from day 0 to day 28. The outcome was ' 'assessed on days 3, 7, 14, 21, and 28 through phone calls. Results: Seventy-seven patients ' 'were randomly allocated to Favipiravir and placebo groups. There was no significant ' 'difference between groups considering baseline characteristics. During the study period, ' '10.5% of patients in the Favipiravir group and 5.1% of patients in the placebo group were ' 'hospitalized, but there was no significant difference between them (p-value = 0.3). No ' 'adverse event was reported in the treatment group. Conclusions: Our study shows that ' 'Favipiravir did not reduce the hospitalization rate of mild to moderate COVID-19 patients in ' 'outpatient settings.</jats:p>', 'DOI': '10.3390/arm91010004', 'type': 'journal-article', 'created': {'date-parts': [[2023, 1, 30]], 'date-time': '2023-01-30T16:25:47Z', 'timestamp': 1675095947000}, 'page': '18-25', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Favipiravir in the Treatment of Outpatient COVID-19: A Multicenter, Randomized, Triple-Blind, ' 'Placebo-Controlled Clinical Trial', 'prefix': '10.3390', 'volume': '91', 'author': [ { 'ORCID': 'http://orcid.org/0000-0002-1829-0494', 'authenticated-orcid': False, 'given': 'Atefeh', 'family': 'Vaezi', 'sequence': 'first', 'affiliation': [ { 'name': 'Cancer Prevention Research Center, Isfahan University of Medical ' 'Sciences, Isfahan 8174673461, Iran'}]}, { 'given': 'Mehrzad', 'family': 'Salmasi', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Internal Medicine, School of Medicine, Isfahan ' 'University of Medical Sciences, Isfahan 8174673461, Iran'}]}, { 'given': 'Forogh', 'family': 'Soltaninejad', 'sequence': 'additional', 'affiliation': [ { 'name': 'Bamdad Respiratory and Sleep Research Center, Department of ' 'Internal Medicine, School of Medicine, Isfahan University of ' 'Medical Sciences, Isfahan 8174673461, Iran'}]}, { 'given': 'Mehrdad', 'family': 'Salahi', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Infectious Disease, School of Medicine, Isfahan ' 'University of Medical Sciences, Isfahan 8174673461, Iran'}]}, { 'given': 'Shaghayegh Haghjooy', 'family': 'Javanmard', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Physiology, Applied Physiology Research Center, ' 'Cardiovascular Research Institute, Isfahan University of Medical ' 'Sciences, Isfahan 8174673461, Iran'}]}, { 'ORCID': 'http://orcid.org/0000-0001-9606-7434', 'authenticated-orcid': False, 'given': 'Babak', 'family': 'Amra', 'sequence': 'additional', 'affiliation': [ { 'name': 'Bamdad Respiratory and Sleep Research Center, Department of ' 'Internal Medicine, School of Medicine, Isfahan University of ' 'Medical Sciences, Isfahan 8174673461, Iran'}]}], 'member': '1968', 'published-online': {'date-parts': [[2023, 1, 28]]}, 'reference': [ { 'key': 'ref_1', 'unstructured': 'Worldometer (2022, October 01). COVID-19 Pandemic. Available online: ' 'https://www.worldometers.info/coronavirus/.'}, { 'key': 'ref_2', 'doi-asserted-by': 'crossref', 'unstructured': 'Dessie, Z.G., and Zewotir, T. (2021). Mortality-related risk factors of ' 'COVID-19: A systematic review and meta-analysis of 42 studies and ' '423,117 patients. BMC Infect. Dis., 21.', 'DOI': '10.1186/s12879-021-06536-3'}, { 'key': 'ref_3', 'first-page': '1', 'article-title': 'The economic burden of coronavirus disease 2019 (COVID-19): Evidence ' 'from Iran', 'volume': '21', 'author': 'Darab', 'year': '2021', 'journal-title': 'BMC Health Serv. Res.'}, { 'key': 'ref_4', 'doi-asserted-by': 'crossref', 'first-page': 'eabc7112', 'DOI': '10.1126/sciadv.abc7112', 'article-title': 'Potency and timing of antiviral therapy as determinants of duration of ' 'SARS-CoV-2 shedding and intensity of inflammatory response', 'volume': '6', 'author': 'Goyal', 'year': '2020', 'journal-title': 'Sci. 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