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0 0.5 1 1.5 2+ Mortality 13% Improvement Relative Risk Ventilation -2% Progression 18% Favipiravir  Tsuzuki et al.  EARLY TREATMENT Is early treatment with favipiravir beneficial for COVID-19? Retrospective 7,654 patients in Japan Lower mortality (p=0.59) and progression (p=0.098), not sig. c19early.org Tsuzuki et al., Infectious Diseases an.., Mar 2022 Favors favipiravir Favors control

Effectiveness of Favipiravir on Nonsevere, Early-Stage COVID-19 in Japan: A Large Observational Study Using the COVID-19 Registry Japan

Tsuzuki et al., Infectious Diseases and Therapy, doi:10.1007/s40121-022-00617-9
Mar 2022  
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Retrospective database analysis of 7,654 hospitalized patients in Japan, showing no significant differences with favipiravir treatment. NCGM-G-003494-0.
risk of death, 13.1% lower, HR 0.87, p = 0.59, treatment 2,532, control 5,122, adjusted per study, day 30.
risk of mechanical ventilation, 2.0% higher, HR 1.02, p = 0.93, treatment 2,532, control 5,122, adjusted per study, IMV/ECMO.
risk of progression, 17.5% lower, HR 0.82, p = 0.10, treatment 2,532, control 5,122, adjusted per study, oxygen requirement.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Tsuzuki et al., 21 Mar 2022, retrospective, Japan, peer-reviewed, 21 authors, average treatment delay 4.0 days.
This PaperFavipiravirAll
Effectiveness of Favipiravir on Nonsevere, Early-Stage COVID-19 in Japan: A Large Observational Study Using the COVID-19 Registry Japan
Shinya Tsuzuki, Kayoko Hayakawa, Yohei Doi, Tomohiro Shinozaki, Yukari Uemura, Nobuaki Matsunaga, Mari Terada, Setsuko Suzuki, Yusuke Asai, Gen Yamada, Sho Saito, Taro Shibata, Masashi Kondo, Kazuo Izumi, Masayuki Hojo, Tetsuya Mizoue, Kazuhisa Yokota, Fukumi Nakamura-Uchiyama, Fumitake Saito, Wataru Sugiura, Norio Ohmagari
Infectious Diseases and Therapy, doi:10.1007/s40121-022-00617-9
Introduction: Several randomized controlled trials have compared the effectiveness of favipiravir with that of placebo. However, evidence regarding its effect on nonsevere, early-stage coronavirus disease 2019 (COVID-19) remains insufficient. Methods: We used the COVID-19 Registry Japan, a nationwide registry of inpatients with COVID-19, for evaluating the effectiveness of favipiravir on patients with nonsevere, earlystage COVID-19. Eligible patients, who did not need supplementary oxygen therapy at admission, were classified according to two regimens (starting favipiravir therapy within 4 days from admission vs. no favipiravir during hospitalization) and were then compared using a threestep method (cloning, censoring, and
Ethics Author Contributions. Shinya Tsuzuki, Kayoko Hayakawa, Yohei Doi, Wataru Sugiura, and Norio Ohmagari conceived the study. Tomohiro Shinozaki and Yukari Uemura designed analysis. Nobuaki Matsunaga, Mari Terada, Setsuko Suzuki, Yusuke Asai, Taro Shibata, Masahi Kondo, Kazuo Izumi, Masahiro Hojo, Tetsuya Mizoue, Kazuhisa Yokota, Fukumi Nakamura-Uchiyama, and Fumitake Saito collected the data. Shinya Tsuzuki, Kayoko Hayakawa, Yohei Doi, Tomohiro Shinozaki, Yukari Uemura, Sho Saito, and Gen Yamada analyzed and interpreted the data. Shinya Tsuzuki wrote the first draft, which was subsequently revised by all authors. All authors read and approved the final manuscript. Disclosures. Yohei Doi received scholarship donation from Shionogi & Co., Ltd., honorarium from Merck & Co., Shionogi & Co., Ltd., FUJIFILM Toyama Chemical Co., Ltd., and Teijin Pharma Limited, consultant fee from Shionogi & Co., Ltd., Meiji Seika Pharma Co., Ltd., Gilead Sciences, Inc., bioMe ´rieux S.A., GlaxoSmithKline plc, Merck & Co., and Chugai Pharmaceutical Co., Ltd. Shinya Tsuzuki, Kayoko Hayakawa, Tomohiro Shinozaki, Yukari Uemura, Nobuaki Matsunaga, Mari Terada, Setsuko Suzuki, Yusuke Asai, Gen Yamada, Sho Saito, Taro Shibata, Masashi Kondo, Kazuo Izumi, Masayuki Hojo, Tetsuya Mizoue, Kazuhisa Yokota, Fukumi Nakamura-Uchiyama, Fumitake Saito, Wataru Sugiura, Norio Ohmagari all have nothing to disclose. Compliance with Ethics Guidelines. This study was approved by the NCGM ethics..
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' '2020;181:379–81.', 'volume': '181', 'year': '2020'}, { 'DOI': '10.1093/cid/ciaa415', 'author': 'J Lighter', 'doi-asserted-by': 'publisher', 'first-page': '896', 'journal-title': 'Clin Infect Dis', 'key': '617_CR27', 'unstructured': 'Lighter J, Phillips M, Hochman S, et al. Obesity in patients younger ' 'than 60 years is a risk factor for COVID-19 hospital admission. Clin ' 'Infect Dis. 2020;71:896–7.', 'volume': '71', 'year': '2020'}, { 'DOI': '10.7326/M20-3742', 'author': 'SY Tartof', 'doi-asserted-by': 'publisher', 'first-page': '773', 'journal-title': 'Ann Intern Med', 'key': '617_CR28', 'unstructured': 'Tartof SY, Qian L, Hong V, et al. Obesity and mortality among patients ' 'diagnosed with COVID-19: results from an integrated health care ' 'organization. Ann Intern Med. 2020;173:773–81.', 'volume': '173', 'year': '2020'}, { 'key': '617_CR29', 'unstructured': 'R Core Team. R: a language and environment for statistical computing. ' 'Vienna, Austria: R Foundation for Statistical Computing; 2018.'}, { 'key': '617_CR30', 'unstructured': 'Appili Therapeutics provides update on phase 3 PRESECO clinical trial ' 'evaluating Avigan®/Reeqonus™. Appili—LIVE. ' 'https://www.appilitherapeutics.com/newsfeed/Appili-Therapeutics-Provides-Update-on-Phase-3-PRESECO-Clinical-Trial-Evaluating-Avigan%C2%AE%2FReeqonus%E2%84%A2. ' 'Accessed 17 Nov 2021.'}, { 'key': '617_CR31', 'unstructured': 'National Institutes of Health. Information on COVID-19 treatment, ' 'prevention and research. COVID-19 treatment guidelines. ' 'https://www.covid19treatmentguidelines.nih.gov/. Accessed 27 Jan 2021.'}, { 'key': '617_CR32', 'unstructured': 'World Health Organization. Therapeutics and COVID-19: living guideline. ' 'https://www.who.int/publications-detail-redirect/therapeutics-and-covid-19-living-guideline. ' 'Accessed 27 Jan 2021.'}, { 'key': '617_CR33', 'unstructured': 'CDC. Coronavirus disease 2019 (COVID-19). Centers for Disease Control ' 'and Prevention. 2020. ' 'https://www.cdc.gov/coronavirus/2019-ncov/index.html. Accessed 12 Aug ' '2021.'}, { 'key': '617_CR34', 'unstructured': 'Prime Minister’s Office of Japan. About novel coronavirus vaccine. ' 'https://www.kantei.go.jp/jp/headline/kansensho/vaccine.html. Accessed 18 ' 'Nov 2021.'}, { 'key': '617_CR35', 'unstructured': 'Ritchie H, Mathieu E, Rodés-Guirao L, et al. Coronavirus pandemic ' '(COVID-19). Our world in data. 2020. ' 'https://ourworldindata.org/covid-vaccinations. Accessed 18 Nov 2021.'}, { 'DOI': '10.1016/j.antiviral.2018.03.003', 'author': 'L Delang', 'doi-asserted-by': 'publisher', 'first-page': '85', 'journal-title': 'Antivir Res', 'key': '617_CR36', 'unstructured': 'Delang L, Abdelnabi R, Neyts J. Favipiravir as a potential ' 'countermeasure against neglected and emerging RNA viruses. Antivir Res. ' '2018;153:85–94.', 'volume': '153', 'year': '2018'}, { 'DOI': '10.1016/S2055-6640(20)30016-9', 'author': 'V Pilkington', 'doi-asserted-by': 'publisher', 'first-page': '45', 'journal-title': 'J Virus Erad', 'key': '617_CR37', 'unstructured': 'Pilkington V, Pepperrell T, Hill A. A review of the safety of ' 'favipiravir—a potential treatment in the COVID-19 pandemic? J Virus ' 'Erad. 2020;6:45–51.', 'volume': '6', 'year': '2020'}, { 'DOI': '10.1080/14787210.2021.1866545', 'author': 'SM Hashemian', 'doi-asserted-by': 'publisher', 'first-page': '1029', 'journal-title': 'Expert Rev Anti Infect Ther', 'key': '617_CR38', 'unstructured': 'Hashemian SM, Farhadi T, Velayati AA. A review on favipiravir: the ' 'properties, function, and usefulness to treat COVID-19. Expert Rev Anti ' 'Infect Ther. 2021;19:1029–37.', 'volume': '19', 'year': '2021'}, { 'DOI': '10.1093/biomet/70.1.41', 'author': 'PR Rosenbaum', 'doi-asserted-by': 'publisher', 'first-page': '41', 'journal-title': 'Biometrilca', 'key': '617_CR39', 'unstructured': 'Rosenbaum PR, Rubin DB. The central role of the propensity score in ' 'observational studies for causal effects. Biometrilca. 1983;70:41–55.', 'volume': '70', 'year': '1983'}], 'reference-count': 39, 'references-count': 39, 'relation': {}, 'resource': {'primary': {'URL': 'https://link.springer.com/10.1007/s40121-022-00617-9'}}, 'score': 1, 'short-container-title': ['Infect Dis Ther'], 'short-title': [], 'source': 'Crossref', 'subject': ['Infectious Diseases', 'Microbiology (medical)'], 'subtitle': [], 'title': [ 'Effectiveness of Favipiravir on Nonsevere, Early-Stage COVID-19 in Japan: A Large ' 'Observational Study Using the COVID-19 Registry Japan'], 'type': 'journal-article', 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy'}
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Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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