Clinical antiviral efficacy of favipiravir in early COVID-19 (PLATCOV): an open-label, randomised, controlled, adaptive platform trial
Abstract Brief summary In early symptomatic COVID-19 treatment, high dose oral favipiravir did not accelerate viral clearance. Background Favipiravir, an anti-influenza drug, has in vitro antiviral activity against SARS-CoV-2. Clinical trial evidence to date is inconclusive. Favipiravir has been rec...
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| Language: | English |
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BMC
2024-01-01
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| Series: | BMC Infectious Diseases |
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| Online Access: | https://doi.org/10.1186/s12879-023-08835-3 |
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| author | Viravarn Luvira William H. K. Schilling Podjanee Jittamala James A. Watson Simon Boyd Tanaya Siripoon Thundon Ngamprasertchai Pedro J. Almeida Maneerat Ekkapongpisit Cintia Cruz James J. Callery Shivani Singh Runch Tuntipaiboontana Varaporn Kruabkontho Thatsanun Ngernseng Jaruwan Tubprasert Mohammad Yazid Abdad Srisuda Keayarsa Wanassanan Madmanee Renato S. Aguiar Franciele M. Santos Pongtorn Hanboonkunupakarn Borimas Hanboonkunupakarn Kittiyod Poovorawan Mallika Imwong Walter R. J. Taylor Vasin Chotivanich Kesinee Chotivanich Sasithon Pukrittayakamee Arjen M. Dondorp Nicholas P. J. Day Mauro M. Teixeira Watcharapong Piyaphanee Weerapong Phumratanaprapin Nicholas J. White the PLATCOV Collaborative Group |
| author_facet | Viravarn Luvira William H. K. Schilling Podjanee Jittamala James A. Watson Simon Boyd Tanaya Siripoon Thundon Ngamprasertchai Pedro J. Almeida Maneerat Ekkapongpisit Cintia Cruz James J. Callery Shivani Singh Runch Tuntipaiboontana Varaporn Kruabkontho Thatsanun Ngernseng Jaruwan Tubprasert Mohammad Yazid Abdad Srisuda Keayarsa Wanassanan Madmanee Renato S. Aguiar Franciele M. Santos Pongtorn Hanboonkunupakarn Borimas Hanboonkunupakarn Kittiyod Poovorawan Mallika Imwong Walter R. J. Taylor Vasin Chotivanich Kesinee Chotivanich Sasithon Pukrittayakamee Arjen M. Dondorp Nicholas P. J. Day Mauro M. Teixeira Watcharapong Piyaphanee Weerapong Phumratanaprapin Nicholas J. White the PLATCOV Collaborative Group |
| author_sort | Viravarn Luvira |
| collection | DOAJ |
| description | Abstract Brief summary In early symptomatic COVID-19 treatment, high dose oral favipiravir did not accelerate viral clearance. Background Favipiravir, an anti-influenza drug, has in vitro antiviral activity against SARS-CoV-2. Clinical trial evidence to date is inconclusive. Favipiravir has been recommended for the treatment of COVID-19 in some countries. Methods In a multicentre open-label, randomised, controlled, adaptive platform trial, low-risk adult patients with early symptomatic COVID-19 were randomised to one of ten treatment arms including high dose oral favipiravir (3.6g on day 0 followed by 1.6g daily to complete 7 days treatment) or no study drug. The primary outcome was the rate of viral clearance (derived under a linear mixed-effects model from the daily log10 viral densities in standardised duplicate oropharyngeal swab eluates taken daily over 8 days [18 swabs per patient]), assessed in a modified intention-to-treat population (mITT). The safety population included all patients who received at least one dose of the allocated intervention. This ongoing adaptive platform trial was registered at ClinicalTrials.gov (NCT05041907) on 13/09/2021. Results In the final analysis, the mITT population contained data from 114 patients randomised to favipiravir and 126 patients randomised concurrently to no study drug. Under the linear mixed-effects model fitted to all oropharyngeal viral density estimates in the first 8 days from randomisation (4,318 swabs), there was no difference in the rate of viral clearance between patients given favipiravir and patients receiving no study drug; a -1% (95% credible interval: -14 to 14%) difference. High dose favipiravir was well-tolerated. Interpretation Favipiravir does not accelerate viral clearance in early symptomatic COVID-19. The viral clearance rate estimated from quantitative measurements of oropharyngeal eluate viral densities assesses the antiviral efficacy of drugs in vivo with comparatively few studied patients. |
| first_indexed | 2024-03-08T12:40:12Z |
| format | Article |
| id | doaj.art-38be8586c0b14f9a9e31989e8009d6df |
| institution | Directory Open Access Journal |
| issn | 1471-2334 |
| language | English |
| last_indexed | 2024-03-08T12:40:12Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Infectious Diseases |
| spelling | doaj.art-38be8586c0b14f9a9e31989e8009d6df2024-01-21T12:12:10ZengBMCBMC Infectious Diseases1471-23342024-01-0124111010.1186/s12879-023-08835-3Clinical antiviral efficacy of favipiravir in early COVID-19 (PLATCOV): an open-label, randomised, controlled, adaptive platform trialViravarn Luvira0William H. K. Schilling1Podjanee Jittamala2James A. Watson3Simon Boyd4Tanaya Siripoon5Thundon Ngamprasertchai6Pedro J. Almeida7Maneerat Ekkapongpisit8Cintia Cruz9James J. Callery10Shivani Singh11Runch Tuntipaiboontana12Varaporn Kruabkontho13Thatsanun Ngernseng14Jaruwan Tubprasert15Mohammad Yazid Abdad16Srisuda Keayarsa17Wanassanan Madmanee18Renato S. Aguiar19Franciele M. Santos20Pongtorn Hanboonkunupakarn21Borimas Hanboonkunupakarn22Kittiyod Poovorawan23Mallika Imwong24Walter R. J. Taylor25Vasin Chotivanich26Kesinee Chotivanich27Sasithon Pukrittayakamee28Arjen M. Dondorp29Nicholas P. J. Day30Mauro M. Teixeira31Watcharapong Piyaphanee32Weerapong Phumratanaprapin33Nicholas J. White34the PLATCOV Collaborative GroupDepartment of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol UniversityMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityDepartment of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol UniversityDepartment of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol UniversityClinical Research Unit, Center for Advanced and Innovative Therapies, Universidade Federal de Minas GeraisMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityDepartment of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol UniversityMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityDepartment of Genetics, Ecology and Evolution, Institute of Biological Sciences, Universidade Federal de Minas GeraisDepartment of Genetics, Ecology and Evolution, Institute of Biological Sciences, Universidade Federal de Minas GeraisBangplee Hospital, Ministry of Public HealthDepartment of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol UniversityDepartment of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol UniversityMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityDepartment of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol UniversityFaculty of Medicine, Navamindradhiraj UniversityDepartment of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol UniversityDepartment of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol UniversityMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityClinical Research Unit, Center for Advanced and Innovative Therapies, Universidade Federal de Minas GeraisDepartment of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol UniversityDepartment of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol UniversityMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityAbstract Brief summary In early symptomatic COVID-19 treatment, high dose oral favipiravir did not accelerate viral clearance. Background Favipiravir, an anti-influenza drug, has in vitro antiviral activity against SARS-CoV-2. Clinical trial evidence to date is inconclusive. Favipiravir has been recommended for the treatment of COVID-19 in some countries. Methods In a multicentre open-label, randomised, controlled, adaptive platform trial, low-risk adult patients with early symptomatic COVID-19 were randomised to one of ten treatment arms including high dose oral favipiravir (3.6g on day 0 followed by 1.6g daily to complete 7 days treatment) or no study drug. The primary outcome was the rate of viral clearance (derived under a linear mixed-effects model from the daily log10 viral densities in standardised duplicate oropharyngeal swab eluates taken daily over 8 days [18 swabs per patient]), assessed in a modified intention-to-treat population (mITT). The safety population included all patients who received at least one dose of the allocated intervention. This ongoing adaptive platform trial was registered at ClinicalTrials.gov (NCT05041907) on 13/09/2021. Results In the final analysis, the mITT population contained data from 114 patients randomised to favipiravir and 126 patients randomised concurrently to no study drug. Under the linear mixed-effects model fitted to all oropharyngeal viral density estimates in the first 8 days from randomisation (4,318 swabs), there was no difference in the rate of viral clearance between patients given favipiravir and patients receiving no study drug; a -1% (95% credible interval: -14 to 14%) difference. High dose favipiravir was well-tolerated. Interpretation Favipiravir does not accelerate viral clearance in early symptomatic COVID-19. The viral clearance rate estimated from quantitative measurements of oropharyngeal eluate viral densities assesses the antiviral efficacy of drugs in vivo with comparatively few studied patients.https://doi.org/10.1186/s12879-023-08835-3FavipiravirSARS-CoV-2COVID-19Early treatmentAntiviral efficacyPharmacometrics |
| spellingShingle | Viravarn Luvira William H. K. Schilling Podjanee Jittamala James A. Watson Simon Boyd Tanaya Siripoon Thundon Ngamprasertchai Pedro J. Almeida Maneerat Ekkapongpisit Cintia Cruz James J. Callery Shivani Singh Runch Tuntipaiboontana Varaporn Kruabkontho Thatsanun Ngernseng Jaruwan Tubprasert Mohammad Yazid Abdad Srisuda Keayarsa Wanassanan Madmanee Renato S. Aguiar Franciele M. Santos Pongtorn Hanboonkunupakarn Borimas Hanboonkunupakarn Kittiyod Poovorawan Mallika Imwong Walter R. J. Taylor Vasin Chotivanich Kesinee Chotivanich Sasithon Pukrittayakamee Arjen M. Dondorp Nicholas P. J. Day Mauro M. Teixeira Watcharapong Piyaphanee Weerapong Phumratanaprapin Nicholas J. White the PLATCOV Collaborative Group Clinical antiviral efficacy of favipiravir in early COVID-19 (PLATCOV): an open-label, randomised, controlled, adaptive platform trial BMC Infectious Diseases Favipiravir SARS-CoV-2 COVID-19 Early treatment Antiviral efficacy Pharmacometrics |
| title | Clinical antiviral efficacy of favipiravir in early COVID-19 (PLATCOV): an open-label, randomised, controlled, adaptive platform trial |
| title_full | Clinical antiviral efficacy of favipiravir in early COVID-19 (PLATCOV): an open-label, randomised, controlled, adaptive platform trial |
| title_fullStr | Clinical antiviral efficacy of favipiravir in early COVID-19 (PLATCOV): an open-label, randomised, controlled, adaptive platform trial |
| title_full_unstemmed | Clinical antiviral efficacy of favipiravir in early COVID-19 (PLATCOV): an open-label, randomised, controlled, adaptive platform trial |
| title_short | Clinical antiviral efficacy of favipiravir in early COVID-19 (PLATCOV): an open-label, randomised, controlled, adaptive platform trial |
| title_sort | clinical antiviral efficacy of favipiravir in early covid 19 platcov an open label randomised controlled adaptive platform trial |
| topic | Favipiravir SARS-CoV-2 COVID-19 Early treatment Antiviral efficacy Pharmacometrics |
| url | https://doi.org/10.1186/s12879-023-08835-3 |
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