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Favipiravir in patients hospitalised with COVID-19 (PIONEER trial): a multicentre, open-label, phase 3, randomised controlled trial of early intervention versus standard care
BACKGROUND: COVID-19 has overwhelmed health services globally. Oral antiviral therapies are licensed worldwide, but indications and efficacy rates vary. We aimed to evaluate the safety and efficacy of oral favipiravir in patients hospitalised with COVID-19. METHODS: We conducted a multicentre, open-...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Author(s). Published by Elsevier Ltd.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9891737/ https://www.ncbi.nlm.nih.gov/pubmed/36528039 http://dx.doi.org/10.1016/S2213-2600(22)00412-X |
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author | Shah, Pallav L Orton, Christopher M Grinsztejn, Beatriz Donaldson, Gavin C Crabtree Ramírez, Brenda Tonkin, James Santos, Breno R Cardoso, Sandra W Ritchie, Andrew I Conway, Francesca Riberio, Maria P D Wiseman, Dexter J Tana, Anand Vijayakumar, Bavithra Caneja, Cielito Leaper, Craig Mann, Bobby Samson, Anda Bhavsar, Pankaj K Boffito, Marta Johnson, Mark R Pozniak, Anton Pelly, Michael |
author_facet | Shah, Pallav L Orton, Christopher M Grinsztejn, Beatriz Donaldson, Gavin C Crabtree Ramírez, Brenda Tonkin, James Santos, Breno R Cardoso, Sandra W Ritchie, Andrew I Conway, Francesca Riberio, Maria P D Wiseman, Dexter J Tana, Anand Vijayakumar, Bavithra Caneja, Cielito Leaper, Craig Mann, Bobby Samson, Anda Bhavsar, Pankaj K Boffito, Marta Johnson, Mark R Pozniak, Anton Pelly, Michael |
author_sort | Shah, Pallav L |
collection | PubMed |
description | BACKGROUND: COVID-19 has overwhelmed health services globally. Oral antiviral therapies are licensed worldwide, but indications and efficacy rates vary. We aimed to evaluate the safety and efficacy of oral favipiravir in patients hospitalised with COVID-19. METHODS: We conducted a multicentre, open-label, randomised controlled trial of oral favipiravir in adult patients who were newly admitted to hospital with proven or suspected COVID-19 across five sites in the UK (n=2), Brazil (n=2) and Mexico (n=1). Using a permuted block design, eligible and consenting participants were randomly assigned (1:1) to receive oral favipiravir (1800 mg twice daily for 1 day; 800 mg twice daily for 9 days) plus standard care, or standard care alone. All caregivers and patients were aware of allocation and those analysing data were aware of the treatment groups. The prespecified primary outcome was the time from randomisation to recovery, censored at 28 days, which was assessed using an intention-to-treat approach. Post-hoc analyses were used to assess the efficacy of favipiravir in patients aged younger than 60 years, and in patients aged 60 years and older. The trial was registered with clinicaltrials.gov, NCT04373733. FINDINGS: Between May 5, 2020 and May 26, 2021, we assessed 503 patients for eligibility, of whom 499 were randomly assigned to favipiravir and standard care (n=251) or standard care alone (n=248). There was no significant difference between those who received favipiravir and standard care, relative to those who received standard care alone in time to recovery in the overall study population (hazard ratio [HR] 1·06 [95% CI 0·89–1·27]; n=499; p=0·52). Post-hoc analyses showed a faster rate of recovery in patients younger than 60 years who received favipiravir and standard care versus those who had standard care alone (HR 1·35 [1·06–1·72]; n=247; p=0·01). 36 serious adverse events were observed in 27 (11%) of 251 patients administered favipiravir and standard care, and 33 events were observed in 27 (11%) of 248 patients receiving standard care alone, with infectious, respiratory, and cardiovascular events being the most numerous. There was no significant between-group difference in serious adverse events per patient (p=0·87). INTERPRETATION: Favipiravir does not improve clinical outcomes in all patients admitted to hospital with COVID-19, however, patients younger than 60 years might have a beneficial clinical response. The indiscriminate use of favipiravir globally should be cautioned, and further high-quality studies of antiviral agents, and their potential treatment combinations, are warranted in COVID-19. FUNDING: LifeArc and CW+. |
format | Online Article Text |
id | pubmed-9891737 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The Author(s). Published by Elsevier Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-98917372023-02-02 Favipiravir in patients hospitalised with COVID-19 (PIONEER trial): a multicentre, open-label, phase 3, randomised controlled trial of early intervention versus standard care Shah, Pallav L Orton, Christopher M Grinsztejn, Beatriz Donaldson, Gavin C Crabtree Ramírez, Brenda Tonkin, James Santos, Breno R Cardoso, Sandra W Ritchie, Andrew I Conway, Francesca Riberio, Maria P D Wiseman, Dexter J Tana, Anand Vijayakumar, Bavithra Caneja, Cielito Leaper, Craig Mann, Bobby Samson, Anda Bhavsar, Pankaj K Boffito, Marta Johnson, Mark R Pozniak, Anton Pelly, Michael Lancet Respir Med Articles BACKGROUND: COVID-19 has overwhelmed health services globally. Oral antiviral therapies are licensed worldwide, but indications and efficacy rates vary. We aimed to evaluate the safety and efficacy of oral favipiravir in patients hospitalised with COVID-19. METHODS: We conducted a multicentre, open-label, randomised controlled trial of oral favipiravir in adult patients who were newly admitted to hospital with proven or suspected COVID-19 across five sites in the UK (n=2), Brazil (n=2) and Mexico (n=1). Using a permuted block design, eligible and consenting participants were randomly assigned (1:1) to receive oral favipiravir (1800 mg twice daily for 1 day; 800 mg twice daily for 9 days) plus standard care, or standard care alone. All caregivers and patients were aware of allocation and those analysing data were aware of the treatment groups. The prespecified primary outcome was the time from randomisation to recovery, censored at 28 days, which was assessed using an intention-to-treat approach. Post-hoc analyses were used to assess the efficacy of favipiravir in patients aged younger than 60 years, and in patients aged 60 years and older. The trial was registered with clinicaltrials.gov, NCT04373733. FINDINGS: Between May 5, 2020 and May 26, 2021, we assessed 503 patients for eligibility, of whom 499 were randomly assigned to favipiravir and standard care (n=251) or standard care alone (n=248). There was no significant difference between those who received favipiravir and standard care, relative to those who received standard care alone in time to recovery in the overall study population (hazard ratio [HR] 1·06 [95% CI 0·89–1·27]; n=499; p=0·52). Post-hoc analyses showed a faster rate of recovery in patients younger than 60 years who received favipiravir and standard care versus those who had standard care alone (HR 1·35 [1·06–1·72]; n=247; p=0·01). 36 serious adverse events were observed in 27 (11%) of 251 patients administered favipiravir and standard care, and 33 events were observed in 27 (11%) of 248 patients receiving standard care alone, with infectious, respiratory, and cardiovascular events being the most numerous. There was no significant between-group difference in serious adverse events per patient (p=0·87). INTERPRETATION: Favipiravir does not improve clinical outcomes in all patients admitted to hospital with COVID-19, however, patients younger than 60 years might have a beneficial clinical response. The indiscriminate use of favipiravir globally should be cautioned, and further high-quality studies of antiviral agents, and their potential treatment combinations, are warranted in COVID-19. FUNDING: LifeArc and CW+. The Author(s). Published by Elsevier Ltd. 2023-05 2022-12-14 /pmc/articles/PMC9891737/ /pubmed/36528039 http://dx.doi.org/10.1016/S2213-2600(22)00412-X Text en © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Articles Shah, Pallav L Orton, Christopher M Grinsztejn, Beatriz Donaldson, Gavin C Crabtree Ramírez, Brenda Tonkin, James Santos, Breno R Cardoso, Sandra W Ritchie, Andrew I Conway, Francesca Riberio, Maria P D Wiseman, Dexter J Tana, Anand Vijayakumar, Bavithra Caneja, Cielito Leaper, Craig Mann, Bobby Samson, Anda Bhavsar, Pankaj K Boffito, Marta Johnson, Mark R Pozniak, Anton Pelly, Michael Favipiravir in patients hospitalised with COVID-19 (PIONEER trial): a multicentre, open-label, phase 3, randomised controlled trial of early intervention versus standard care |
title | Favipiravir in patients hospitalised with COVID-19 (PIONEER trial): a multicentre, open-label, phase 3, randomised controlled trial of early intervention versus standard care |
title_full | Favipiravir in patients hospitalised with COVID-19 (PIONEER trial): a multicentre, open-label, phase 3, randomised controlled trial of early intervention versus standard care |
title_fullStr | Favipiravir in patients hospitalised with COVID-19 (PIONEER trial): a multicentre, open-label, phase 3, randomised controlled trial of early intervention versus standard care |
title_full_unstemmed | Favipiravir in patients hospitalised with COVID-19 (PIONEER trial): a multicentre, open-label, phase 3, randomised controlled trial of early intervention versus standard care |
title_short | Favipiravir in patients hospitalised with COVID-19 (PIONEER trial): a multicentre, open-label, phase 3, randomised controlled trial of early intervention versus standard care |
title_sort | favipiravir in patients hospitalised with covid-19 (pioneer trial): a multicentre, open-label, phase 3, randomised controlled trial of early intervention versus standard care |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9891737/ https://www.ncbi.nlm.nih.gov/pubmed/36528039 http://dx.doi.org/10.1016/S2213-2600(22)00412-X |
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