Favipiravir and Hydroxychloroquine Combination Therapy in Patients with Moderate to Severe COVID-19 (FACCT Trial): An Open-Label, Multicenter, Randomized, Controlled Trial
Mohammad Bosaeed, Ebrahim Mahmoud, Ahmad Alharbi, Hadeel Altayib, Hawra Albayat, Faisal Alharbi, Khalid Ghalilah, Abdulmajid Al Arfaj, Jumana Aljishi, Abdullatif Alarfaj, Hajar Alqahtani, Badriah M Almutairi, Manar Almaghaslah, Nawaf M Alyahya, Abdullah Bawazir, Saud Aleisa, Abdulrahman Alsaedy, Abderrezak Bouchama, Malak Alharbi, Majid Alshamrani, Sameera Al Johani, Majed Aljeraisy, Mohammed Alzahrani, Abdulhakeem O Althaqafi, Hassan Almarhabi, Athari Alotaibi, Nasser Alqahtani, Yaseen M Arabi, Omar S Aldibasi, Ahmad Alaskar
Infectious Diseases and Therapy, doi:10.1007/s40121-021-00496-6
Introduction: Antiviral drugs have shown limited effectiveness in treating patients with coronavirus disease 2019 (COVID-19). We aimed to assess the effects of a favipiravir and hydroxychloroquine combination on treating moderate-to-severe COVID-19 patients. Methods: An investigator-initiated, multicenter, open-label, randomized trial at nine hospitals. Eligible patients were adults with moderate-to-severe COVID-19 defined as
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.
Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
Beigel, Tomashek, Dodd, Remdesivir for the treatment of Covid-19-final report, N Engl J Med
Bosaeed, Hussein, 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
Boulware, Pullen, Bangdiwala, A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19, N Engl J Med
Cavalcanti, Zampieri, Rosa, Hydroxychloroquine with or without azithromycin in mild-to-moderate Covid-19, N Engl J Med
Chen, Zhang, Huang, Favipiravir versus Arbidol for COVID-19: a randomized clinical trial
Contributions, Alharbi, Alqahtani, Alsaedy, Alshamrani et al., Study design: Mahmoud
Dabbous, Abd-Elsalam, El-Sayed, Efficacy of favipiravir in COVID-19 treatment: a multi-center randomized study, Arch Virol
Delang, Abdelnabi, Neyts, Favipiravir as a potential countermeasure against neglected and emerging RNA viruses, Antivir Res
Doni, Hibino, Hase, A prospective, randomized, open-label trial of early versus late favipiravir therapy in hospitalized patients with COVID-19, Antimicrob Agents Chemother
Furuta, Komeno, Nakamura, Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase, Proc Jpn Acad Ser B Phys Biol Sci
Gordon, Mouncey, Investigators, Interleukin-6 receptor antagonists in critically ill patients with Covid-19, N Engl J Med
Gupta, Hayek, Wang, Factors associated with death in critically ill patients with coronavirus disease 2019 in the US, JAMA Intern Med
Horby, Lim, Recovery Collaborative Group, Dexamethasone in hospitalized patients with Covid-19, N Engl J Med
Ivashchenko, Dmitriev, Vostokova, AVIFAVIR for treatment of patients with moderate COVID-19: interim results of a Phase II/III multicenter randomized clinical trial, Clin Infect Dis Off Publ Infect Dis Soc Am
Lemaitre, Solas, Gre ´goire, Potential drug-drug interactions associated with drugs currently proposed for COVID-19 treatment in patients receiving other treatments, Fundam Clin Pharmacol
Pan, Peto, Solidarity, Repurposed antiviral drugs for Covid-19-interim WHO solidarity trial results, N Engl J Med
Rosenberg, Dufort, Udo, Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York State, JAMA
Rosenthal, Cao, Gundrum, Sianis, Safo, Risk factors associated with in-hospital mortality in a US national sample of patients with COVID-19, JAMA Netw Open
Salama, Han, Yau, Tocilizumab in patients hospitalized with Covid-19 pneumonia, N Engl J Med
Singh, Ryan, Kredo, Chaplin, Fletcher, Chloroquine or hydroxychloroquine for prevention and treatment of COVID-19, Cochrane Database Syst Rev
Solaymani-Dodaran, Ghanei, Bagheri, Safety and efficacy of Favipiravir in moderate to severe SARS-CoV-2 pneumonia, Int Immunopharmacol
Spinner, Gottlieb, Criner, Effect of remdesivir vs standard care on clinical status at 11 days in patients with moderate COVID-19: a randomized clinical trial, JAMA
Udwadia, Singh, Barkate, Efficacy and safety of favipiravir, an oral RNA-dependent RNA polymerase inhibitor, in mild-to-moderate COVID-19: A randomized, comparative, open-label, multicenter, phase 3 clinical trial, Int J Infect Dis IJID Off Publ Int Soc Infect Dis
Wang, Cao, Zhang, Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res
Wang, Zhang, Du, Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial, Lancet Lond Engl
Wu, Mcgoogan, Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention, JAMA
Yao, Ye, Zhang, In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Clin Infect Dis
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'journal-issue': {'issue': '4', 'published-print': {'date-parts': [[2021, 12]]}},
'alternative-id': ['496'],
'URL': 'http://dx.doi.org/10.1007/s40121-021-00496-6',
'relation': {},
'ISSN': ['2193-8229', '2193-6382'],
'subject': ['Infectious Diseases', 'Microbiology (medical)'],
'container-title-short': 'Infect Dis Ther',
'published': {'date-parts': [[2021, 7, 28]]},
'assertion': [ { 'value': '3 June 2021',
'order': 1,
'name': 'received',
'label': 'Received',
'group': {'name': 'ArticleHistory', 'label': 'Article History'}},
{ 'value': '1 July 2021',
'order': 2,
'name': 'accepted',
'label': 'Accepted',
'group': {'name': 'ArticleHistory', 'label': 'Article History'}},
{ 'value': '28 July 2021',
'order': 3,
'name': 'first_online',
'label': 'First Online',
'group': {'name': 'ArticleHistory', 'label': 'Article History'}}]}