Safety and efficacy of favipiravir versus hydroxychloroquine in management of COVID-19: A randomised controlled trial

{ 'indexed': {'date-parts': [[2024, 5, 11]], 'date-time': '2024-05-11T00:26:51Z', 'timestamp': 1715387211870}, 'reference-count': 30, 'publisher': 'Springer Science and Business Media LLC', 'issue': '1', 'license': [ { 'start': { 'date-parts': [[2021, 3, 31]], 'date-time': '2021-03-31T00:00:00Z', 'timestamp': 1617148800000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}, { 'start': { 'date-parts': [[2021, 3, 31]], 'date-time': '2021-03-31T00:00:00Z', 'timestamp': 1617148800000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}], 'content-domain': {'domain': ['link.springer.com'], 'crossmark-restriction': False}, 'abstract': '<jats:title>Abstract</jats:title><jats:p><jats:italic>Favipiravir</jats:italic> is considered ' 'a potential treatment for COVID-19 due its efficacy against different viral infections. We ' 'aimed to explore the safety and efficacy of <jats:italic>favipiravir</jats:italic> in ' 'treatment of COVID-19 mild and moderate cases. It was randomized-controlled open-label ' 'interventional phase 3 clinical trial [NCT04349241]. 100 patients were recruited from 18th ' 'April till 18th May. 50 patients received favipiravir 3200\xa0mg at day 1 followed by 600\xa0' 'mg twice (day 2–day 10). 50 patients received hydroxychloroquine 800\xa0mg at day 1 followed ' 'by 200\xa0mg twice (day 2–10) and oral oseltamivir 75\xa0mg/12\xa0h/day for 10\xa0days. ' 'Patients were enrolled from Ain Shams University Hospital and Assiut University Hospital. ' 'Both arms were comparable as regards demographic characteristics and comorbidities. The ' 'average onset of SARS-CoV-2 PCR negativity was 8.1 and 8.3\xa0days in HCQ-arm and ' 'favipiravir-arm respectively. 55.1% of those on HCQ-arm turned PCR negative at/or before 7th ' 'day from diagnosis compared to 48% in favipiravir-arm (p\u2009=\u20090.7). 4 patients in FVP ' 'arm developed transient transaminitis on the other hand heartburn and nausea were reported in ' 'about 20 patients in HCQ-arm. Only one patient in HCQ-arm died after developing acute ' 'myocarditis resulted in acute heart failure. Favipiravir is a safe effective alternative for ' 'hydroxychloroquine in mild or moderate COVID-19 infected patients.</jats:p>', 'DOI': '10.1038/s41598-021-85227-0', 'type': 'journal-article', 'created': {'date-parts': [[2021, 3, 31]], 'date-time': '2021-03-31T10:03:51Z', 'timestamp': 1617185031000}, 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 24, 'title': 'RETRACTED ARTICLE: Safety and efficacy of favipiravir versus hydroxychloroquine in management of ' 'COVID-19: A randomised controlled trial', 'prefix': '10.1038', 'volume': '11', 'author': [ {'given': 'Hany M.', 'family': 'Dabbous', 'sequence': 'first', 'affiliation': []}, {'given': 'Manal H.', 'family': 'El-Sayed', 'sequence': 'additional', 'affiliation': []}, {'given': 'Gihan', 'family': 'El Assal', 'sequence': 'additional', 'affiliation': []}, {'given': 'Hesham', 'family': 'Elghazaly', 'sequence': 'additional', 'affiliation': []}, {'given': 'Fatma F. S.', 'family': 'Ebeid', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ahmed F.', 'family': 'Sherief', 'sequence': 'additional', 'affiliation': []}, {'given': 'Maha', 'family': 'Elgaafary', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ehab', 'family': 'Fawzy', 'sequence': 'additional', 'affiliation': []}, {'given': 'Sahar M.', 'family': 'Hassany', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ahmed R.', 'family': 'Riad', 'sequence': 'additional', 'affiliation': []}, {'given': 'Mohamed A.', 'family': 'TagelDin', 'sequence': 'additional', 'affiliation': []}], 'member': '297', 'published-online': {'date-parts': [[2021, 3, 31]]}, 'reference': [ { 'key': '85227_CR1', 'doi-asserted-by': 'publisher', 'first-page': '497e506', 'DOI': '10.1016/S0140-6736(20)30183-5', 'volume': '395', 'author': 'C Huang', 'year': '2020', 'unstructured': 'Huang, C. et al. Clinical features of patients infected with 2019 novel ' 'coronavirus in Wuhan, China. Lancet 395, 497e506 (2020).', 'journal-title': 'Lancet'}, { 'key': '85227_CR2', 'unstructured': 'World Health Organization. ' '.https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports. ' 'Accessed on 3/1/2021.'}, { 'key': '85227_CR3', 'first-page': '514e23', 'volume': '395', 'author': 'JF Chan', 'year': '2020', 'unstructured': 'Chan, J. F. et al. A familial cluster of pneumonia associated with the ' '2019 novel coronavirus indicating person-to-person transmission: a study ' 'of a family cluster. Lancet 395, 514e23 (2020).', 'journal-title': 'Lancet'}, { 'key': '85227_CR4', 'unstructured': 'Egyptian Ministry of Health. ' 'https://www.care.gov.eg/EgyptCare/Index.aspx. Accessed 3/1/2021.'}, { 'key': '85227_CR5', 'doi-asserted-by': 'publisher', 'first-page': '1192', 'DOI': '10.1016/j.eng.2020.03.007', 'volume': '6', 'author': 'Q Cai', 'year': '2020', 'unstructured': 'Cai, Q. et al. Experimental treatment with favipiravir for COVID-19: An ' 'open-label control study. Engineering 6, 1192–1198 (2020).', 'journal-title': 'Engineering'}, { 'key': '85227_CR6', 'doi-asserted-by': 'publisher', 'first-page': '70', 'DOI': '10.1016/j.antiviral.2015.08.015', 'volume': '123', 'author': 'V Madelain', 'year': '2015', 'unstructured': 'Madelain, V. et al. Ebola virus dynamics in mice treated with ' 'favipiravir. Antiviral Res. 123, 70–77 (2015).', 'journal-title': 'Antiviral Res.'}, { 'issue': '7', 'key': '85227_CR7', 'doi-asserted-by': 'publisher', 'first-page': '449', 'DOI': '10.2183/pjab.93.027', 'volume': '93', 'author': 'Y Furuta', 'year': '2017', 'unstructured': 'Furuta, Y., Komeno, T. & Nakamura, T. Favipiravir (T-705), a broad ' 'spectrum inhibitor of viral RNA polymerase. Proc. Jpn. Acad. Ser. B ' 'Phys. Biol. Sci. 93(7), 449–463 (2017).', 'journal-title': 'Proc. Jpn. Acad. Ser. B Phys. Biol. Sci.'}, { 'issue': '2', 'key': '85227_CR8', 'doi-asserted-by': 'publisher', 'first-page': '176', 'DOI': '10.1097/QCO.0000000000000532', 'volume': '32', 'author': 'FG Hayden', 'year': '2019', 'unstructured': 'Hayden, F. G. & Shindo, N. Influenza virus polymerase inhibitors in ' 'clinical development. Curr. Opin. Infect. Dis. 32(2), 176–186 (2019).', 'journal-title': 'Curr. Opin. Infect. Dis.'}, { 'key': '85227_CR9', 'unstructured': 'Zhonghua, J., He, H., Hu, X. & Za, Z. Expert consensus on chloroquine ' 'phosphate for the treatment of novel coronavirus pneumonia. 43, E019 ' '(2020).'}, { 'issue': '369', 'key': '85227_CR10', 'doi-asserted-by': 'publisher', 'first-page': 'm1849', 'DOI': '10.1136/bmj.m1849', 'volume': '14', 'author': 'W Tang', 'year': '2020', 'unstructured': 'Tang, W. et al. Hydroxychloroquine in patients with mainly mild to ' 'moderate coronavirus disease 2019: Open label, randomised controlled ' 'trial. BMJ 14(369), m1849 (2020).', 'journal-title': 'BMJ'}, { 'key': '85227_CR11', 'unstructured': 'Zhou, D., Dai, S. M. & Tong, Q. COVID-19: A recommendation to examine ' 'the effect of hydroxychloroquine in preventing infection and ' 'progression. J. Antimicrob. Chemother., dkaa114.'}, { 'key': '85227_CR12', 'doi-asserted-by': 'publisher', 'first-page': 'Article 16', 'DOI': '10.1038/s41421-020-0156-0', 'volume': '6', 'author': 'J Liu', 'year': '2020', 'unstructured': 'Liu, J. et al. Hydroxychloroquine, a less toxic derivative of ' 'chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. ' 'Cell Discov. 6, Article 16 (2020).', 'journal-title': 'Cell Discov.'}, { 'issue': '1', 'key': '85227_CR13', 'doi-asserted-by': 'publisher', 'first-page': '72', 'DOI': '10.5582/bst.2020.01047', 'volume': '14', 'author': 'J Gao', 'year': '2020', 'unstructured': 'Gao, J., Tian, Z. & Yang, X. Breakthrough: Chloroquine phosphate has ' 'shown apparent efficacy in treatment of COVID-19 associated pneumonia in ' 'clinical studies. Biosci. Trends 14(1), 72–73 (2020).', 'journal-title': 'Biosci. Trends'}, { 'key': '85227_CR14', 'unstructured': 'Information for Clinicians on Investigational Therapeutics for Patients ' 'with COVID-19. ' 'https://www.cdc.gov/coronavirus/2019-ncov/hcp/therapeutic-options.html.'}, { 'key': '85227_CR15', 'unstructured': 'Food and Drug Administration. www.fda.gov/media/138945/download.'}, { 'key': '85227_CR16', 'unstructured': 'American College of Cardiology. Ventricular arrhythmia risk due to ' 'hydroxychloroquine-azithromycin treatment for COVID-19. ' 'https://www.acc.org/latest-in-cardiology/articles/2020/03/27/14/00/.'}, { 'issue': '3', 'key': '85227_CR17', 'doi-asserted-by': 'publisher', 'first-page': '269', 'DOI': '10.1038/s41422-020-0282-0', 'volume': '30', 'author': 'M Wang', 'year': '2020', 'unstructured': 'Wang, M. et al. Remdesivir and chloroquine effectively inhibit the ' 'recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. ' '30(3), 269–271 (2020).', 'journal-title': 'Cell Res.'}, { 'key': '85227_CR18', 'doi-asserted-by': 'publisher', 'DOI': '10.1101/2020.03.17.20037432v4', 'author': 'C Chen', 'year': '2020', 'unstructured': 'Chen, C., Zhang, Y., Huang, J. & Yin, P. Favipiravir versus arbidol for ' 'COVID-19: A randomized clinical trial. medRxiv ' 'https://doi.org/10.1101/2020.03.17.20037432v4 (2020).', 'journal-title': 'medRxiv'}, { 'key': '85227_CR19', 'doi-asserted-by': 'publisher', 'first-page': '45', 'DOI': '10.1016/S2055-6640(20)30016-9', 'volume': '6', 'author': 'V Pilkington', 'year': '2020', '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. 6, 45–51 (2020).', 'journal-title': 'J. Virus Erad.'}, { 'issue': '4S', 'key': '85227_CR20', 'first-page': 'S351', 'volume': '23', 'author': 'CM de Barros', 'year': '2020', 'unstructured': 'de Barros, C. M. et al. COVID-19 pandemic—A narrative review of the ' 'potential roles of chloroquine and hydroxychloroquine. Pain Physician ' '23(4S), S351–S366 (2020).', 'journal-title': 'Pain Physician'}, { 'issue': '10229', 'key': '85227_CR21', 'doi-asserted-by': 'publisher', 'first-page': '1054', 'DOI': '10.1016/S0140-6736(20)30566-3', 'volume': '395', 'author': 'F Zhou', 'year': '2020', 'unstructured': 'Zhou, F. et al. Clinical course and risk factors for mortality of adult ' 'inpatients with COVID-19 in Wuhan, China: A retrospective cohort study ' '[published correction appears in Lancet. 2020 Mar 28;395(10229):1038]. ' 'Lancet 395(10229), 1054–1062 (2020).', 'journal-title': 'Lancet'}, { 'key': '85227_CR22', 'first-page': '215', 'volume': '49', 'author': 'C Jun', 'year': '2020', 'unstructured': 'Jun, C. et al. A pilot study of hydroxychloroquine in treatment of ' 'patients with common coronavirus disease-19 (COVID-19). J. Zhejiang ' 'Univ. 49, 215–219 (2020).', 'journal-title': 'J. Zhejiang Univ.'}, { 'key': '85227_CR23', 'doi-asserted-by': 'publisher', 'DOI': '10.1101/2020.03.22.20040758v3', 'author': 'Z Chen', 'year': '2020', 'unstructured': 'Chen, Z. et al. Efficacy of hydroxychloroquine in patients with ' 'COVID-19: Results of a randomized clinical trial. medRxiv ' 'https://doi.org/10.1101/2020.03.22.20040758v3 (2020).', 'journal-title': 'medRxiv'}, { 'key': '85227_CR24', 'doi-asserted-by': 'publisher', 'first-page': 'm1844', 'DOI': '10.1136/bmj.m1844', 'volume': '369', 'author': 'M Mahevas', 'year': '2020', 'unstructured': 'Mahevas, M. et al. No evidence of clinical efficacy of ' 'hydroxychloroquine in patients hospitalized for COVID-19 infection with ' 'oxygen requirement: Results of a study using routinely collected data to ' 'emulate a target trial. BMJ 369, m1844 (2020).', 'journal-title': 'BMJ'}, { 'key': '85227_CR25', 'doi-asserted-by': 'publisher', 'DOI': '10.1101/2020.04.10.20060558v2', 'author': 'W Tang', 'year': '2020', 'unstructured': 'Tang, W. et al. Hydroxychloroquine in patients mainly with mild to ' 'moderate COVID-19: An open-label, randomized, controlled trial. medRxiv ' 'https://doi.org/10.1101/2020.04.10.20060558v2 (2020).', 'journal-title': 'medRxiv'}, { 'key': '85227_CR26', 'doi-asserted-by': 'publisher', 'DOI': '10.1101/2020.04.16.20065920v1.full.pdf', 'author': 'J Magagnoli', 'year': '2020', 'unstructured': 'Magagnoli, J. et al. Outcomes of hydroxychloroquine usage in United ' 'States veterans hospitalized with COVID-19. medRxiv ' 'https://doi.org/10.1101/2020.04.16.20065920v1.full.pdf (2020).', 'journal-title': 'medRxiv'}, { 'issue': '4', 'key': '85227_CR27', 'doi-asserted-by': 'publisher', 'first-page': 'e208857', 'DOI': '10.1001/jamanetworkopen.2020.8857', 'volume': '3', 'author': 'M Borba', 'year': '2020', 'unstructured': 'Borba, M. et al. Chloroquine diphosphate in two different dosages as ' 'adjunctive therapy of hospitalized patients with severe respiratory ' 'syndrome in the context of coronavirus (SARS-CoV-2) infection: ' 'Preliminary safety results of a randomized, double-blinded, phase IIb ' 'clinical trial (CloroCovid-19 Study). JAMA Netw. Open 3(4), e208857. ' 'https://doi.org/10.1001/jamanetworkopen.2020.8857 (2020).', 'journal-title': 'JAMA Netw. Open'}, { 'key': '85227_CR28', 'doi-asserted-by': 'publisher', 'first-page': '2411', 'DOI': '10.1056/NEJMoa2012410', 'volume': '382', 'author': 'J Geleris', 'year': '2020', 'unstructured': 'Geleris, J., Sun, Y., Platt, J. & Zucker, J. Observational study of ' 'hydroxychloroquine in hospitalized patients with COVID-19. N. Engl. J. ' 'Med. 382, 2411–2418 (2020).', 'journal-title': 'N. Engl. J. Med.'}, { 'issue': '5', 'key': '85227_CR29', 'doi-asserted-by': 'publisher', 'first-page': '96', 'DOI': '10.3390/ph13050096', 'volume': '13', 'author': 'M Saber-Ayad', 'year': '2020', 'unstructured': 'Saber-Ayad, M., Saleh, M. A. & Abu-Gharbieh, E. The rationale for ' 'potential pharmacotherapy of COVID-19. Pharmaceuticals 13(5), 96 (2020).', 'journal-title': 'Pharmaceuticals'}, { 'issue': '1', 'key': '85227_CR30', 'doi-asserted-by': 'publisher', 'first-page': '904', 'DOI': '10.1186/s13063-020-04825-x.PMID:33129363;PMCID:PMC7602769', 'volume': '21', 'author': 'M Bosaeed', 'year': '2020', 'unstructured': 'Bosaeed, M. et al. A trial of favipiravir and hydroxychloroquine ' 'combination in adults hospitalized with moderate and severe Covid-19: A ' 'structured summary of a study protocol for a randomised controlled ' 'trial. Trials 21(1), 904. ' 'https://doi.org/10.1186/s13063-020-04825-x.PMID:33129363;PMCID:PMC7602769 ' '(2020).', 'journal-title': 'Trials'}], 'container-title': 'Scientific Reports', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://www.nature.com/articles/s41598-021-85227-0.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://www.nature.com/articles/s41598-021-85227-0', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://www.nature.com/articles/s41598-021-85227-0.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2022, 12, 3]], 'date-time': '2022-12-03T06:12:31Z', 'timestamp': 1670047951000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.nature.com/articles/s41598-021-85227-0'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2021, 3, 31]]}, 'references-count': 30, 'journal-issue': {'issue': '1', 'published-online': {'date-parts': [[2021, 12]]}}, 'alternative-id': ['85227'], 'URL': 'http://dx.doi.org/10.1038/s41598-021-85227-0', 'relation': { 'has-preprint': [ { 'id-type': 'doi', 'id': '10.21203/rs.3.rs-83677/v2', 'asserted-by': 'object'}, { 'id-type': 'doi', 'id': '10.21203/rs.3.rs-83677/v1', 'asserted-by': 'object'}]}, 'ISSN': ['2045-2322'], 'subject': [], 'container-title-short': 'Sci Rep', 'published': {'date-parts': [[2021, 3, 31]]}, 'assertion': [ { 'value': '22 September 2020', 'order': 1, 'name': 'received', 'label': 'Received', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '25 February 2021', 'order': 2, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '31 March 2021', 'order': 3, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '18 September 2021', 'order': 4, 'name': 'change_date', 'label': 'Change Date', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': 'Correction', 'order': 5, 'name': 'change_type', 'label': 'Change Type', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': 'This article has been retracted. Please see the Retraction Notice for more ' 'detail:', 'order': 6, 'name': 'change_details', 'label': 'Change Details', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': 'https://doi.org/10.1038/s41598-021-98683-5', 'URL': 'https://doi.org/10.1038/s41598-021-98683-5', 'order': 7, 'name': 'change_details', 'label': 'Change Details', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': 'The authors declare no competing interests.', 'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}], 'article-number': '7282'}