A Prospective, Randomized, Open-Label Trial of Early versus Late Favipiravir Therapy in Hospitalized Patients with COVID-19

Doi et al., Antimicrobial Agents and Chemotherapy, doi:10.1128/AAC.01897-20, Nov 2020

Small RCT comparing late and very late (7 and 14 days from fever onset) favipiravir. Viral clearance was non-statistically significantly improved with relatively early treatment. There was a reduction in time to defervescence, and a significant improvement in fever was observed the day after starting therapy. There was no progression or mortality. While limited by the small sample size, authors conclude that the results suggest antiviral activity of favipiravir in this patient population. There was no control group.

Potential risks of favipiravir include the creation of dangerous variants, and mutagenicity, carcinogenicity, teratogenicity, and embryotoxicity1-6.

Important missing comments or errors? Let us know.

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.

6. Cenikli et al., Does Favipiravir interact with DNA? Design of electrochemical DNA nanobiosensor to investigate the interaction between DNA and Favipiravir used in the treatment of COVID-19, Talanta, doi:10.1016/j.talanta.2025.128084.sciencedirect.com, doi.org.

Doi et al., 17 Nov 2020, Randomized Controlled Trial, peer-reviewed, 45 authors.

This Paper Favipiravir All

Abstract: ANTIVIRAL AGENTS crossm A Prospective, Randomized, Open-Label Trial of Early versus Late Favipiravir Therapy in Hospitalized Patients with COVID-19 Yohei Doi,a,b Masaya Hibino,c Ryota Hase,a,d Michiko Yamamoto,e Yu Kasamatsu,f Masahiro Hirose,g Yoshikazu Mutoh,h Yoshito Homma,i Masaki Terada,j Taku Ogawa,k Fumihiro Kashizaki,l Toshihiko Yokoyama,m Hayato Koba,n Hideki Kasahara,o Kazuhisa Yokota,p Hideaki Kato,q Junichi Yoshida,r Toshiyuki Kita,s Yasuyuki Kato,t Tadashi Kamio,u Nobuhiro Kodama,v Yujiro Uchida,w Nobuhiro Ikeda,x Masahiro Shinoda,y Atsushi Nakagawa,z Hiroki Nakatsumi,aa Tomoya Horiguchi,bb Mitsunaga Iwata,c Akifumi Matsuyama,cc Sumi Banno,dd Takenao Koseki,dd,ee Mayumi Teramachi,dd Masami Miyata,dd Shigeru Tajima,ff Takahiro Maeki,ff Eri Nakayama,ff Satoshi Taniguchi,ff Chang Kweng Lim,ff Masayuki Saijo,ff Takumi Imai,gg Hisako Yoshida,gg Daijiro Kabata,gg Ayumi Shintani,gg Yukio Yuzawa,hh Masashi Kondobb,dd a Departments of Microbiology and Infectious Diseases, Fujita Health University School of Medicine, Toyoake, Aichi, Japan b Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA c Department of Emergency and General Internal Medicine, Fujita Health University School of Medicine, Toyoake, Aichi, Japan d Department of Infectious Diseases, Japanese Red Cross Narita Hospital, Narita, Chiba, Japan e Department of Respiratory Medicine, Sagamihara Kyodo Hospital, Sagamihara, Kanagawa, Japan f Infection Control and Clinical Laboratory, Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan g Department of Respiratory Medicine, Fujita Health University Bantane Hospital, Nagoya, Aichi, Japan h Department of Infectious Diseases, Tosei General Hospital, Seto, Aichi, Japan i Department of Respiratory Medicine, Ehime Prefectural Central Hospital, Matsuyama, Ehime, Japan j Department of Respiratory Medicine, Saiseikai Niigata Hospital, Niigata, Niigata, Japan k Center for Infectious Diseases, Nara Medical University, Kashihara, Nara, Japan l Department of Respiratory Medicine, Isehara Kyodo Hospital, Isehara, Kanagawa, Japan m Department of Respiratory Medicine, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Aichi, Japan n o Department of Rheumatology, NTT East Sapporo Hospital, Sapporo, Hokkaido, Japan p Department of Infectious Diseases, Tokyo Metropolitan Health and Medical Corporation Ebara Hospital, Ohta, Tokyo, Japan q Infection Prevention and Control Department, Yokohama City University Hospital, Yokohama, Kanagawa, Japan r Department of Chest Surgery, Shimonoseki City Hospital, Shimonoseki, Yamaguchi, Japan s Department of Respiratory Medicine, National Hospital Organization Kanazawa Medical Center, Kanazawa, Ishikawa, Japan t Department of Infectious Diseases, International University of Health and Welfare Narita Hospital, Narita, Chiba, Japan u Department of Intensive Care, Shonan Kamakura General Hospital, Kamakura, Kanagawa, Japan v Department of General Internal Medicine, Fukuoka Tokushukai Hospital, Kasuga, Fukuoka, Japan w Department of General Medicine, Kitakyushu Municipal Medical Center, Kitakyushu, Fukuoka, Japan x Department of General Internal Medicine, Eiju General Hospital, Taito, Tokyo, Japan y Department of Respiratory Medicine, Tokyo Shinagawa Hospital, Shinagawa, Tokyo, Japan z Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan aa Department of..

DOI record: { "DOI": "10.1128/aac.01897-20", "ISSN": [ "0066-4804", "1098-6596" ], "URL": "http://dx.doi.org/10.1128/AAC.01897-20", "abstract": "Favipiravir is an oral broad-spectrum inhibitor of viral RNA-dependent RNA polymerase that is approved for treatment of influenza in Japan. We conducted a prospective, randomized, open-label, multicenter trial of favipiravir for the treatment of COVID-19 at 25 hospitals across Japan. Eligible patients were adolescents and adults admitted with COVID-19 who were asymptomatic or mildly ill and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomly assigned at a 1:1 ratio to early or late favipiravir therapy (in the latter case, the same regimen starting on day 6 instead of day 1).", "alternative-id": [ "10.1128/AAC.01897-20" ], "assertion": [ { "group": { "label": "Publication History", "name": "publication_history" }, "label": "Received", "name": "received", "order": 0, "value": "2020-09-03" }, { "group": { "label": "Publication History", "name": "publication_history" }, "label": "Accepted", "name": "accepted", "order": 1, "value": "2020-09-16" }, { "group": { "label": "Publication History", "name": "publication_history" }, "label": "Published", "name": "published", "order": 2, "value": "2020-11-17" } ], "author": [ { "ORCID": "http://orcid.org/0000-0002-9620-2525", "affiliation": [ { "name": "Departments of Microbiology and Infectious Diseases, Fujita Health University School of Medicine, Toyoake, Aichi, Japan" }, { "name": "Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA" } ], "authenticated-orcid": false, "family": "Doi", "given": "Yohei", "sequence": "first" }, { "affiliation": [ { "name": "Department of Emergency and General Internal Medicine, Fujita Health University School of Medicine, Toyoake, Aichi, Japan" } ], "family": "Hibino", "given": "Masaya", "sequence": "additional" }, { "affiliation": [ { "name": "Departments of Microbiology and Infectious Diseases, Fujita Health University School of Medicine, Toyoake, Aichi, Japan" }, { "name": "Department of Infectious Diseases, Japanese Red Cross Narita Hospital, Narita, Chiba, Japan" } ], "family": "Hase", "given": "Ryota", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Respiratory Medicine, Sagamihara Kyodo Hospital, Sagamihara, Kanagawa, Japan" } ], "family": "Yamamoto", "given": "Michiko", "sequence": "additional" }, { "affiliation": [ { "name": "Infection Control and Clinical Laboratory, Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan" } ], "family": "Kasamatsu", "given": "Yu", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Respiratory Medicine, Fujita Health University Bantane Hospital, Nagoya, Aichi, Japan" } ], "family": "Hirose", "given": "Masahiro", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-7368-3004", "affiliation": [ { "name": "Department of Infectious Diseases, Tosei General Hospital, Seto, Aichi, Japan" } ], "authenticated-orcid": false, "family": "Mutoh", "given": "Yoshikazu", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Respiratory Medicine, Ehime Prefectural Central Hospital, Matsuyama, Ehime, Japan" } ], "family": "Homma", "given": "Yoshito", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Respiratory Medicine, Saiseikai Niigata Hospital, Niigata, Niigata, Japan" } ], "family": "Terada", "given": "Masaki", "sequence": "additional" }, { "affiliation": [ { "name": "Center for Infectious Diseases, Nara Medical University, Kashihara, Nara, Japan" } ], "family": "Ogawa", "given": "Taku", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Respiratory Medicine, Isehara Kyodo Hospital, Isehara, Kanagawa, Japan" } ], "family": "Kashizaki", "given": "Fumihiro", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Respiratory Medicine, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Aichi, Japan" } ], "family": "Yokoyama", "given": "Toshihiko", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Respiratory Medicine, Komatsu Municipal Hospital, Komatsu, Ishikawa, Japan" } ], "family": "Koba", "given": "Hayato", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Rheumatology, NTT East Sapporo Hospital, Sapporo, Hokkaido, Japan" } ], "family": "Kasahara", "given": "Hideki", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Infectious Diseases, Tokyo Metropolitan Health and Medical Corporation Ebara Hospital, Ohta, Tokyo, Japan" } ], "family": "Yokota", "given": "Kazuhisa", "sequence": "additional" }, { "affiliation": [ { "name": "Infection Prevention and Control Department, Yokohama City University Hospital, Yokohama, Kanagawa, Japan" } ], "family": "Kato", "given": "Hideaki", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Chest Surgery, Shimonoseki City Hospital, Shimonoseki, Yamaguchi, Japan" } ], "family": "Yoshida", "given": "Junichi", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Respiratory Medicine, National Hospital Organization Kanazawa Medical Center, Kanazawa, Ishikawa, Japan" } ], "family": "Kita", "given": "Toshiyuki", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Infectious Diseases, International University of Health and Welfare Narita Hospital, Narita, Chiba, Japan" } ], "family": "Kato", "given": "Yasuyuki", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Intensive Care, Shonan Kamakura General Hospital, Kamakura, Kanagawa, Japan" } ], "family": "Kamio", "given": "Tadashi", "sequence": "additional" }, { "affiliation": [ { "name": "Department of General Internal Medicine, Fukuoka Tokushukai Hospital, Kasuga, Fukuoka, Japan" } ], "family": "Kodama", "given": "Nobuhiro", "sequence": "additional" }, { "affiliation": [ { "name": "Department of General Medicine, Kitakyushu Municipal Medical Center, Kitakyushu, Fukuoka, Japan" } ], "family": "Uchida", "given": "Yujiro", "sequence": "additional" }, { "affiliation": [ { "name": "Department of General Internal Medicine, Eiju General Hospital, Taito, Tokyo, Japan" } ], "family": "Ikeda", "given": "Nobuhiro", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Respiratory Medicine, Tokyo Shinagawa Hospital, Shinagawa, Tokyo, Japan" } ], "family": "Shinoda", "given": "Masahiro", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan" } ], "family": "Nakagawa", "given": "Atsushi", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Respiratory Medicine, Ishikawa Prefectural Central Hospital, Kanazawa, Ishikawa, Japan" } ], "family": "Nakatsumi", "given": "Hiroki", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Respiratory Medicine, Fujita Health University School of Medicine, Toyoake, Aichi, Japan" } ], "family": "Horiguchi", "given": "Tomoya", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Emergency and General Internal Medicine, Fujita Health University School of Medicine, Toyoake, Aichi, Japan" } ], "family": "Iwata", "given": "Mitsunaga", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Regenerative Medicine and Stem Cell Biology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan" } ], "family": "Matsuyama", "given": "Akifumi", "sequence": "additional" }, { "affiliation": [ { "name": "Center for Clinical Trial and Research Support, Fujita Health University School of Medicine, Toyoake, Aichi, Japan" } ], "family": "Banno", "given": "Sumi", "sequence": "additional" }, { "affiliation": [ { "name": "Center for Clinical Trial and Research Support, Fujita Health University School of Medicine, Toyoake, Aichi, Japan" }, { "name": "Department of Clinical Pharmacy, Fujita Health University School of Medicine, Toyoake, Aichi, Japan" } ], "family": "Koseki", "given": "Takenao", "sequence": "additional" }, { "affiliation": [ { "name": "Center for Clinical Trial and Research Support, Fujita Health University School of Medicine, Toyoake, Aichi, Japan" } ], "family": "Teramachi", "given": "Mayumi", "sequence": "additional" }, { "affiliation": [ { "name": "Center for Clinical Trial and Research Support, Fujita Health University School of Medicine, Toyoake, Aichi, Japan" } ], "family": "Miyata", "given": "Masami", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Virology I, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan" } ], "family": "Tajima", "given": "Shigeru", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Virology I, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan" } ], "family": "Maeki", "given": "Takahiro", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Virology I, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan" } ], "family": "Nakayama", "given": "Eri", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Virology I, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan" } ], "family": "Taniguchi", "given": "Satoshi", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Virology I, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan" } ], "family": "Lim", "given": "Chang Kweng", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0001-5458-7298", "affiliation": [ { "name": "Department of Virology I, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan" } ], "authenticated-orcid": false, "family": "Saijo", "given": "Masayuki", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Medical Statistics, Osaka City University Graduate School of Medicine, Osaka, Osaka, Japan" } ], "family": "Imai", "given": "Takumi", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Medical Statistics, Osaka City University Graduate School of Medicine, Osaka, Osaka, Japan" } ], "family": "Yoshida", "given": "Hisako", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Medical Statistics, Osaka City University Graduate School of Medicine, Osaka, Osaka, Japan" } ], "family": "Kabata", "given": "Daijiro", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Medical Statistics, Osaka City University Graduate School of Medicine, Osaka, Osaka, Japan" } ], "family": "Shintani", "given": "Ayumi", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan" } ], "family": "Yuzawa", "given": "Yukio", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Respiratory Medicine, Fujita Health University School of Medicine, Toyoake, Aichi, Japan" }, { "name": "Center for Clinical Trial and Research Support, Fujita Health University School of Medicine, Toyoake, Aichi, Japan" } ], "family": "Kondo", "given": "Masashi", "sequence": "additional" } ], "container-title": "Antimicrobial Agents and Chemotherapy", "container-title-short": "Antimicrob Agents Chemother", "content-domain": { "crossmark-restriction": true, "domain": [ "journals.asm.org" ] }, "created": { "date-parts": [ [ 2020, 9, 22 ] ], "date-time": "2020-09-22T13:47:51Z", "timestamp": 1600782471000 }, "deposited": { "date-parts": [ [ 2022, 2, 21 ] ], "date-time": "2022-02-21T21:39:57Z", "timestamp": 1645479597000 }, "funder": [ { "DOI": "10.13039/100009619", "award": [ "JP19fk0108150" ], "doi-asserted-by": "publisher", "name": "Japan Agency for Medical Research and Development" } ], "indexed": { "date-parts": [ [ 2022, 9, 6 ] ], "date-time": "2022-09-06T09:28:14Z", "timestamp": 1662456494270 }, "is-referenced-by-count": 110, "issue": "12", "issued": { "date-parts": [ [ 2020, 11, 17 ] ] }, "journal-issue": { "issue": "12", "published-print": { "date-parts": [ [ 2020, 11, 17 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2020, 11, 17 ] ], "date-time": "2020-11-17T00:00:00Z", "timestamp": 1605571200000 } }, { "URL": "https://journals.asm.org/non-commercial-tdm-license", "content-version": "tdm", "delay-in-days": 0, "start": { "date-parts": [ [ 2020, 11, 17 ] ], "date-time": "2020-11-17T00:00:00Z", "timestamp": 1605571200000 } } ], "link": [ { "URL": "https://journals.asm.org/doi/pdf/10.1128/AAC.01897-20", "content-type": "application/pdf", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://journals.asm.org/doi/pdf/10.1128/AAC.01897-20", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "235", "original-title": [], "prefix": "10.1128", "published": { "date-parts": [ [ 2020, 11, 17 ] ] }, "published-print": { "date-parts": [ [ 2020, 11, 17 ] ] }, "publisher": "American Society for Microbiology", "reference": [ { "DOI": "10.1001/jama.2020.2648", "doi-asserted-by": "publisher", "key": "e_1_3_3_2_2" }, { "DOI": "10.1016/j.antiviral.2018.03.003", "doi-asserted-by": "publisher", "key": "e_1_3_3_3_2" }, { "DOI": "10.1016/j.antiviral.2013.09.015", "doi-asserted-by": "publisher", "key": "e_1_3_3_4_2" }, { "DOI": "10.1016/j.pharmthera.2020.107512", "doi-asserted-by": "publisher", "key": "e_1_3_3_5_2" }, { "DOI": "10.1016/j.eng.2020.03.007", "doi-asserted-by": "publisher", "key": "e_1_3_3_6_2" }, { "DOI": "10.1093/cid/ciaa1176", "doi-asserted-by": "publisher", "key": "e_1_3_3_7_2" }, { "DOI": "10.1016/j.amjmed.2020.07.003", "doi-asserted-by": "publisher", "key": "e_1_3_3_8_2" }, { "DOI": "10.7883/yoken.JJID.2020.108", "doi-asserted-by": "publisher", "key": "e_1_3_3_9_2" }, { "DOI": "10.1021/acsinfecdis.0c00464", "doi-asserted-by": "publisher", "key": "e_1_3_3_10_2" }, { "DOI": "10.7883/yoken.JJID.2020.061", "doi-asserted-by": "publisher", "key": "e_1_3_3_11_2" }, { "DOI": "10.1620/tjem.251.87", "doi-asserted-by": "publisher", "key": "e_1_3_3_12_2" }, { "DOI": "10.1097/00000421-198212000-00014", "doi-asserted-by": "publisher", "key": "e_1_3_3_13_2" } ], "reference-count": 12, "references-count": 12, "relation": {}, "resource": { "primary": { "URL": "https://journals.asm.org/doi/10.1128/AAC.01897-20" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [ "Infectious Diseases", "Pharmacology (medical)", "Pharmacology" ], "subtitle": [], "title": "A Prospective, Randomized, Open-Label Trial of Early versus Late Favipiravir Therapy in Hospitalized Patients with COVID-19", "type": "journal-article", "update-policy": "http://dx.doi.org/10.1128/asmj-crossmark-policy-page", "volume": "64" }

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. IMA and WCH provide treatment protocols.

Submit

Post

@CovidAnalysis

FAQ

Public domain CC0 1.0