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Favipiravir and Hydroxychloroquine Combination Therapy in Patients with Moderate to Severe COVID19 (FACCT Trial): An Open-Label, Multicenter, Randomized, Controlled Trial

Bosaeed et al., Infect. Dis. Ther., doi:10.1007/s40121-021-00496-6, FACCT, NCT04392973
Apr 2021  
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Mortality 4% Improvement Relative Risk Mortality (b) 29% Mortality (c) -65% Ventilation -8% ICU admission -31% Recovery time -29% Hospitalization time -12% Viral clearance 3% HCQ for COVID-19  FACCT  LATE TREATMENT  RCT Is late treatment with HCQ beneficial for COVID-19? RCT 254 patients in Saudi Arabia (May 2020 - January 2021) Higher ICU admission (p=0.24) and slower recovery (p=0.29), not sig. c19hcq.org Bosaeed et al., Infect. Dis. Ther., Apr 2021 FavorsHCQ Favorscontrol 0 0.5 1 1.5 2+
HCQ for COVID-19
1st treatment shown to reduce risk in March 2020, now with p < 0.00000000001 from 419 studies, recognized in 46 countries.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 109 treatments. c19hcq.org
RCT 254 very late stage (93% on oxygen, 17% in ICU at baseline) hospitalized patients in Saudi Arabia not showing significant differences with HCQ+favipiravir treatment. Only SaO2 < 94% patients were eligible, however the actual SaO2 of enrolled patients is not provided.
Viral load measured by PCR may not accurately reflect infectious virus measured by viral culture. Porter et al. show that viral load early in infection was correlated with infectious virus, but viral load late in infection could be high even with low or undetectable infectious virus. Assessing viral load later in infection may underestimate reductions in infectious virus with treatment.
This study is excluded in the after exclusion results of meta analysis: very late stage, >50% on oxygen/ventilation at baseline.
risk of death, 3.7% lower, RR 0.96, p = 0.91, treatment 14 of 125 (11.2%), control 15 of 129 (11.6%), NNT 234, 90 days.
risk of death, 28.6% lower, RR 0.71, p = 0.45, treatment 9 of 125 (7.2%), control 13 of 129 (10.1%), NNT 35, 28 days.
risk of death, 65.1% higher, RR 1.65, p = 0.68, treatment 8 of 125 (6.4%), control 5 of 129 (3.9%), 14 days.
risk of mechanical ventilation, 8.4% higher, RR 1.08, p = 0.78, treatment 21 of 125 (16.8%), control 20 of 129 (15.5%).
risk of ICU admission, 31.0% higher, RR 1.31, p = 0.24, treatment 33 of 125 (26.4%), control 26 of 129 (20.2%).
recovery time, 28.6% higher, relative time 1.29, p = 0.29, treatment 125, control 129.
hospitalization time, 12.5% higher, relative time 1.12, p = 0.42, treatment 125, control 129.
risk of no viral clearance, 2.6% lower, RR 0.97, p = 0.75, treatment 100 of 125 (80.0%), control 106 of 129 (82.2%), NNT 46.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Bosaeed et al., 30 Apr 2021, Randomized Controlled Trial, Saudi Arabia, peer-reviewed, 30 authors, study period 21 May, 2020 - 26 January, 2021, average treatment delay 5.85 days, trial NCT04392973 (history) (FACCT).
This PaperHCQAll
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.
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' 'Cell Res. 2020;30 (3):269–71.', 'journal-title': 'Cell Res'}, { 'key': '496_CR22', 'first-page': 'CD013587', 'volume': '2', 'author': 'B Singh', 'year': '2021', 'unstructured': 'Singh B, Ryan H, Kredo T, Chaplin M, Fletcher T. Chloroquine or ' 'hydroxychloroquine for prevention and treatment of COVID-19. Cochrane ' 'Database Syst Rev. 2021;2:CD013587.', 'journal-title': 'Cochrane Database Syst Rev.'}, { 'issue': '3', 'key': '496_CR23', 'doi-asserted-by': 'publisher', 'first-page': '949', 'DOI': '10.1007/s00705-021-04956-9', 'volume': '166', 'author': 'HM Dabbous', 'year': '2021', 'unstructured': 'Dabbous HM, Abd-Elsalam S, El-Sayed MH, et al. Efficacy of favipiravir ' 'in COVID-19 treatment: a multi-center randomized study. Arch Virol. ' '2021;166 (3):949–54.', 'journal-title': 'Arch Virol'}, { 'key': '496_CR24', 'first-page': '1176', 'volume': '2', 'author': 'AA Ivashchenko', 'year': '2020', 'unstructured': 'Ivashchenko AA, Dmitriev KA, Vostokova NV, et al. 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. 2020;2:1176.', 'journal-title': 'Clin Infect Dis Off Publ Infect Dis Soc Am'}, { 'key': '496_CR25', 'doi-asserted-by': 'publisher', 'first-page': '107522', 'DOI': '10.1016/j.intimp.2021.107522', 'volume': '95', 'author': 'M Solaymani-Dodaran', 'year': '2021', 'unstructured': 'Solaymani-Dodaran M, Ghanei M, Bagheri M, et al. Safety and efficacy of ' 'Favipiravir in moderate to severe SARS-CoV-2 pneumonia. Int ' 'Immunopharmacol. 2021;95:107522.', 'journal-title': 'Int Immunopharmacol.'}, { 'issue': '21', 'key': '496_CR26', 'doi-asserted-by': 'publisher', 'first-page': '2041', 'DOI': '10.1056/NEJMoa2019014', 'volume': '383', 'author': 'AB Cavalcanti', 'year': '2020', 'unstructured': 'Cavalcanti AB, Zampieri FG, Rosa RG, et al. Hydroxychloroquine with or ' 'without azithromycin in mild-to-moderate Covid-19. N Engl J Med. ' '2020;383 (21):2041–52.', 'journal-title': 'N Engl J Med'}, { 'issue': '12', 'key': '496_CR27', 'doi-asserted-by': 'crossref', 'first-page': 'e01897-20', 'DOI': '10.1128/AAC.01897-20', 'volume': '64', 'author': 'Y Doni', 'year': '2020', 'unstructured': 'Doni Y, Hibino M, Hase R, et al. A prospective, randomized, open-label ' 'trial of early versus late favipiravir therapy in hospitalized patients ' 'with COVID-19. Antimicrob Agents Chemother. 2020;64 (12):e01897-20.', 'journal-title': 'Antimicrob Agents Chemother.'}], 'container-title': 'Infectious Diseases and Therapy', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://link.springer.com/content/pdf/10.1007/s40121-021-00496-6.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/article/10.1007/s40121-021-00496-6/fulltext.html', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/content/pdf/10.1007/s40121-021-00496-6.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 1, 7]], 'date-time': '2023-01-07T02:05:55Z', 'timestamp': 1673057155000}, 'score': 1, 'resource': {'primary': {'URL': 'https://link.springer.com/10.1007/s40121-021-00496-6'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2021, 7, 28]]}, 'references-count': 27, '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'}}]}
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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