Favipiravir in early symptomatic COVID-19, a randomised placebo-controlled trial.

COVID-19 Favipiravir Randomised clinical trial

Journal

EClinicalMedicine
ISSN: 2589-5370
Titre abrégé: EClinicalMedicine
Pays: England
ID NLM: 101733727

Informations de publication

Date de publication:
Dec 2022
Historique:
received: 13 09 2022
revised: 28 09 2022
accepted: 28 09 2022
entrez: 26 10 2022
pubmed: 27 10 2022
medline: 27 10 2022
Statut: epublish

Résumé

Well tolerated antivirals administered early in the course of COVID-19 infection when the viremia is highest could prevent progression to severe disease. Favipiravir inhibits SARS-CoV-2 viral replication People with PCR-confirmed COVID-19 and 5 days or less of symptoms were randomised 1:1 to favipiravir 1800 mg on day 1, then 800 mg twice daily or matched placebo for 14 days. SARS-CoV-2 viral load was quantitated from second daily self-collected nose-throat swabs while receiving study drug. The primary endpoint was time to virological cure defined as 2 successive swabs negative for SARS-CoV-2 by PCR and secondary outcomes were progression of disease severity, symptom resolution and safety. Between 31 July 2020 and 19 September 2021, 200 people were enrolled (199 in the community, 1 in hospital) with 190 receiving one or more doses of drug (modified intention to treat [mITT] population). There was no difference in time to virological cure (Log-rank Favipiravir does not improve the time to virological cure or clinical outcomes and shows no evidence of an antiviral effect when treating early symptomatic COVID-19 infection. The study was supported in part by grants from the Commonwealth Bank Australia, the Lord Mayor's Charitable Foundation, Melbourne Australia and the Orloff Family Charitable Trust, Melbourne, Australia. JHM is supported by the Medical Research Future Fund, AYP, JT are supported by the Australian National Health and Medical Research Council.

Sections du résumé

Background UNASSIGNED
Well tolerated antivirals administered early in the course of COVID-19 infection when the viremia is highest could prevent progression to severe disease. Favipiravir inhibits SARS-CoV-2 viral replication
Methods UNASSIGNED
People with PCR-confirmed COVID-19 and 5 days or less of symptoms were randomised 1:1 to favipiravir 1800 mg on day 1, then 800 mg twice daily or matched placebo for 14 days. SARS-CoV-2 viral load was quantitated from second daily self-collected nose-throat swabs while receiving study drug. The primary endpoint was time to virological cure defined as 2 successive swabs negative for SARS-CoV-2 by PCR and secondary outcomes were progression of disease severity, symptom resolution and safety.
Findings UNASSIGNED
Between 31 July 2020 and 19 September 2021, 200 people were enrolled (199 in the community, 1 in hospital) with 190 receiving one or more doses of drug (modified intention to treat [mITT] population). There was no difference in time to virological cure (Log-rank
Interpretation UNASSIGNED
Favipiravir does not improve the time to virological cure or clinical outcomes and shows no evidence of an antiviral effect when treating early symptomatic COVID-19 infection.
Funding UNASSIGNED
The study was supported in part by grants from the Commonwealth Bank Australia, the Lord Mayor's Charitable Foundation, Melbourne Australia and the Orloff Family Charitable Trust, Melbourne, Australia. JHM is supported by the Medical Research Future Fund, AYP, JT are supported by the Australian National Health and Medical Research Council.

Identifiants

pubmed: 36284645
doi: 10.1016/j.eclinm.2022.101703
pii: S2589-5370(22)00433-3
pmc: PMC9583769
doi:

Types de publication

Journal Article

Langues

eng

Pagination

101703

Informations de copyright

© 2022 The Authors.

Déclaration de conflit d'intérêts

All authors declare no competing interests.

Références

N Engl J Med. 2022 Apr 14;386(15):1475-1477
pubmed: 35263535
Engineering (Beijing). 2020 Oct;6(10):1192-1198
pubmed: 32346491
N Engl J Med. 2022 Feb 10;386(6):509-520
pubmed: 34914868
Front Pharmacol. 2021 Sep 02;12:683296
pubmed: 34539392
Lancet. 2021 Mar 20;397(10279):1063-1074
pubmed: 33676597
Clin Infect Dis. 2022 Aug 24;75(1):e432-e439
pubmed: 34849615
N Engl J Med. 2022 Apr 14;386(15):1397-1408
pubmed: 35172054
Clin Microbiol Infect. 2022 Apr;28(4):602-608
pubmed: 35026375
N Engl J Med. 2021 Feb 25;384(8):693-704
pubmed: 32678530
Nat Commun. 2020 Sep 17;11(1):4682
pubmed: 32943628
Int J Infect Dis. 2021 Feb;103:62-71
pubmed: 33212256
N Engl J Med. 2022 May 5;386(18):1721-1731
pubmed: 35353979
Antimicrob Agents Chemother. 2005 Mar;49(3):981-6
pubmed: 15728892
JAMA. 2022 Apr 5;327(13):1236-1246
pubmed: 35285853
Cell Res. 2020 Mar;30(3):269-271
pubmed: 32020029
Lancet Respir Med. 2021 Dec;9(12):1407-1418
pubmed: 34480861
N Engl J Med. 2022 Jan 27;386(4):305-315
pubmed: 34937145
J Antimicrob Chemother. 2022 Apr 27;77(5):1404-1412
pubmed: 35233617
Trials. 2020 Oct 13;21(1):847
pubmed: 33050947
N Engl J Med. 2020 Nov 19;383(21):2030-2040
pubmed: 33031652
BMJ. 2020 Oct 23;371:m3862
pubmed: 33097561
PLoS Med. 2016 Mar 01;13(3):e1001967
pubmed: 26930627
Emerg Infect Dis. 2020 Aug;26(8):
pubmed: 32396505
J Med Virol. 2022 May;94(5):2284-2289
pubmed: 35043405
Antimicrob Agents Chemother. 2020 Nov 17;64(12):
pubmed: 32958718
Clin Infect Dis. 2022 Apr 21;:
pubmed: 35446944
Nat Commun. 2021 Mar 19;12(1):1735
pubmed: 33741945

Auteurs

James H McMahon (JH)

Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Australia.
Department of Infectious Diseases, Monash Medical Centre, Melbourne, Australia.

Jillian S Y Lau (JSY)

Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Australia.
Department of Infectious Diseases, Monash Medical Centre, Melbourne, Australia.
Department of Infectious Diseases, Eastern Health, Melbourne, Australia.

Anna Coldham (A)

Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Australia.

Janine Roney (J)

Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Australia.

Michelle Hagenauer (M)

Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Australia.

Sally Price (S)

Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Australia.

Mellissa Bryant (M)

Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Australia.

Jill Garlick (J)

Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Australia.

Anne Paterson (A)

Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Australia.

Sue J Lee (SJ)

Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Australia.

Jess O'Bryan (J)

Department of Infectious Diseases, Monash Medical Centre, Melbourne, Australia.

Anna Hearps (A)

Life Sciences Discipline, Burnet Institute, Melbourne, Australia.

Gilda Tachedjian (G)

Life Sciences Discipline, Burnet Institute, Melbourne, Australia.
Department of Microbiology, Monash University, Clayton, Australia.
Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Australia.

Henry Pinskier (H)

Onsite Doctor and OSD.Care, Melbourne, Australia.

Cameron Phillips (C)

Onsite Doctor and OSD.Care, Melbourne, Australia.

Stuart Garrow (S)

Onsite Doctor and OSD.Care, Melbourne, Australia.

Nathan Pinskier (N)

Onsite Doctor and OSD.Care, Melbourne, Australia.

Robert Melvin (R)

Department of Emergency Medicine, Alfred Hospital, Melbourne, Australia.

Luke Blakeway (L)

Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Australia.

Jessica A Wisniewski (JA)

Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Australia.

Sally Byers (S)

Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Australia.

Gnei Z Badoordeen (GZ)

Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Australia.

Stephanie Pereira (S)

Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Australia.

Katherine Pragastis (K)

Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Australia.

Jason A Trubiano (JA)

Department of Infectious Diseases, Austin Hospital, Melbourne, Australia & Department of Medicine, University of Melbourne.

Kyra Y L Chua (KYL)

Department of Infectious Diseases, Austin Hospital, Melbourne, Australia & Department of Medicine, University of Melbourne.

Marion Kainer (M)

Department of Infectious Diseases, Western Health, Melbourne, Australia.

James S Molton (JS)

Department of Infectious Diseases, Western Health, Melbourne, Australia.

Bradley J Gardiner (BJ)

Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Australia.
Epworth Healthcare, Melbourne, Australia.

Anna B Pierce (AB)

Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Australia.
Department of Infectious Diseases, Monash Medical Centre, Melbourne, Australia.
South East Public Health Unit, Monash Health, Melbourne, Australia.

Allen Cheng (A)

Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Australia.

Benjamin A Rogers (BA)

Department of Infectious Diseases, Monash Medical Centre, Melbourne, Australia.
Monash University School of Clinical Sciences at Monash Health, Clayton, Australia.

Anton Y Peleg (AY)

Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Australia.
Infection Theme, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Melbourne, Australia.

Classifications MeSH