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Efficacy and Safety of Favipiravir in Moderate COVID-19 Pneumonia Patients without Oxygen Therapy: A Randomized, Phase III Clinical Trial

Shinkai et al., Infectious Diseases and Therapy, doi:10.1007/s40121-021-00517-4
Aug 2021  
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Time to improvement 37% Improvement Relative Risk Time to improvement (b) 59% Favipiravir  Shinkai et al.  LATE TREATMENT  RCT Is late treatment with favipiravir beneficial for COVID-19? RCT 156 patients in Japan Faster recovery with favipiravir (p=0.014) c19early.org Shinkai et al., Infectious Diseases an.., Aug 2021 Favorsfavipiravir Favorscontrol 0 0.5 1 1.5 2+
RCT 156 patients in Japan, 107 treated with favipiravir, showing significant improvement in a composite outcome defined as the time to improvement in temperature, SpO2, CT findings, and recovery to PCR-.
Potential risks of favipiravir include the creation of dangerous variants, and mutagenicity, carcinogenicity, teratogenicity, and embryotoxicity1-5.
time to improvement, 37.1% lower, HR 0.63, p = 0.01, treatment 107, control 49, adjusted per study, inverted to make HR<1 favor treatment, Cox proportional hazards, composite time to improvement in temperature, SpO2, CT findings, and recovery to PCR-.
time to improvement, 58.5% lower, HR 0.41, p = 0.01, treatment 47, control 13, adjusted per study, inverted to make HR<1 favor treatment, <5 days from onset of fever, Cox proportional hazards, composite time to improvement in temperature, SpO2, CT findings, and recovery to PCR-.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Shinkai et al., 27 Aug 2021, Single Blind Randomized Controlled Trial, Japan, peer-reviewed, 39 authors, average treatment delay 4.8 days.
This PaperFavipiravirAll
Efficacy and Safety of Favipiravir in Moderate COVID-19 Pneumonia Patients without Oxygen Therapy: A Randomized, Phase III Clinical Trial
Masaharu Shinkai, Kenji Tsushima, Shingo Tanaka, Eri Hagiwara, Norihito Tarumoto, Ichiro Kawada, Yuji Hirai, Sho Fujiwara, Yuko Komase, Takeshi Saraya, Hidefumi Koh, Naho Kagiyama, Megumi Shimada, Daiki Kanou, Shinichi Antoku, Yujiro Uchida, Yutaka Tokue, Mikio Takamori, Yasuhiro Gon, Kenya Ie, Yoshitaka Yamazaki, Kazumasa Harada, Naoki Miyao, Takashi Naka, Mitsunaga Iwata, Atsushi Nakagawa, Kazutoshi Hiyama, Yoshihiko Ogawa, Masahiro Shinoda, Shinichiro Ota, Takatomo Hirouchi, Jiro Terada, Shuichi Kawano, Takashi Ogura, Tsutomu Sakurai, Yoshihiko Matsumoto, Hiroyuki Kunishima, Osamu Kobayashi, Satoshi Iwata
Infectious Diseases and Therapy, doi:10.1007/s40121-021-00517-4
Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 , is an enveloped, single-stranded RNA virus. Favipi-ravir is an orally administrable antiviral drug whose mechanism of action is to selectively inhibit RNA-dependent RNA polymerase. A preliminary trial in COVID-19 patients reported significant improvements across a multitude of clinical parameters, but these findings have not been confirmed in an adequate well-controlled trial. We conducted a randomized, single-blind, placebo-controlled Phase III trial assessing the efficacy and safety of favipiravir in patients with Supplementary Information The online version contains supplementary material available at https://
Authorship. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. Authorship Contributions. Conceptualization: Satoshi Iwata, Tsutomu Sakurai; Methodology: Satoshi Iwata, Osamu Kobayashi, Hiroyuki Kunishima, Masaharu Shinkai; Formal analysis: Yoshihiko Matsumoto, Tsutomu Sakurai; Investigation: Masaharu Shinkai, Kenji Tsushima, Shingo Tanaka, Eri Hagiwara, Norihito Tarumoto, Ichiro Kawada, Yuji Hirai, Sho Fujiwara, Yuko Komase, Takeshi Saraya, Hidefumi Koh, Naho Kagiyama, Megumi Shimada, Daiki Kanou, Shinichi Antoku, Yujiro Uchida, Yutaka Tokue, Mikio Takamori, Yasuhiro Gon, Kenya Ie, Yoshitaka Yamazaki, Kazumasa Harada, Naoki Miyao, Takashi Naka, Mitsunaga Iwata, Atsushi Nakagawa, Kazutoshi Hiyama, Yoshihiko Ogawa, Masahiro Shinoda, Shinichiro Ota, Takatomo Hirouchi, Jiro Terada, Shuichi Kawano and Takashi Ogura; Supervision: Satoshi Iwata; Writing -original draft preparation; Masaharu Shinkai. All authors commented on previous versions of the manuscript. All authors read and approved the submitted version. Disclosures. Tsutomu Sakurai and Yoshihiko Matsumoto are employees of the sponsor. Masaharu Shinkai, Kenji Tsushima, Shingo Tanaka, Eri Hagiwara, Norihito Tarumoto, Ichiro Kawada, Yuji Hirai, Sho Fujiwara, Yuko Komase, Takeshi Saraya, Hidefumi Koh, Naho Kagiyama, Megumi..
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Cele, Gazy, Jackson, Escape of SARS-CoV-2 501Y.V2 from neutralization by convalescent plasma, Nature
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Nature. 2021;593:142–6.', 'journal-title': 'Nature'}], 'container-title': 'Infectious Diseases and Therapy', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://link.springer.com/content/pdf/10.1007/s40121-021-00517-4.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/article/10.1007/s40121-021-00517-4/fulltext.html', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/content/pdf/10.1007/s40121-021-00517-4.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2021, 11, 7]], 'date-time': '2021-11-07T14:15:07Z', 'timestamp': 1636294507000}, 'score': 1, 'resource': {'primary': {'URL': 'https://link.springer.com/10.1007/s40121-021-00517-4'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2021, 8, 27]]}, 'references-count': 24, 'journal-issue': {'issue': '4', 'published-print': {'date-parts': [[2021, 12]]}}, 'alternative-id': ['517'], 'URL': 'http://dx.doi.org/10.1007/s40121-021-00517-4', 'relation': {}, 'ISSN': ['2193-8229', '2193-6382'], 'subject': ['Infectious Diseases', 'Microbiology (medical)'], 'container-title-short': 'Infect Dis Ther', 'published': {'date-parts': [[2021, 8, 27]]}, 'assertion': [ { 'value': '21 May 2021', 'order': 1, 'name': 'received', 'label': 'Received', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '27 July 2021', 'order': 2, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '27 August 2021', 'order': 3, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}]}
Late treatment
is less effective
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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