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Favipiravir in Early Symptomatic COVID-19, A Randomised Placebo-Controlled Trial

23 Pages Posted: 14 Jun 2022

See all articles by James H. McMahon

James H. McMahon

Monash University - Department of Infectious Diseases

Jillian S.Y. Lau

Monash University - Department of Infectious Diseases

Anna Coldham

Monash University - Department of Infectious Diseases

Janine Roney

Monash University - Department of Infectious Diseases

Michelle Hagenauer

Monash University - Department of Infectious Diseases

Sally Price

Monash University - Department of Infectious Diseases

Mellissa Bryant

Monash University - Department of Infectious Diseases

Jill Garlick

Monash University - Department of Infectious Diseases

Anne Paterson

Monash University - Department of Infectious Diseases

Sue J. Lee

Monash University - Department of Infectious Diseases

Jess O’Bryan

Monash University - Department of Infectious Diseases

Anna Hearps

Burnet Institute - Life Sciences Discipline

Gilda Tachedjian

Burnet Institute - Life Sciences Discipline

Henry Pinskier

Onsite Doctor and OSD.Care

Cameron Phillips

Onsite Doctor and OSD.Care

Stuart Garrow

Onsite Doctor and OSD.Care

Nathan Pinskier

Onsite Doctor and OSD.Care

Robert Melvin

Onsite Doctor and OSD.Care

Luke Blakeway

Monash University - Department of Infectious Diseases

Jessica A. Wisniewski

Monash University - Department of Infectious Diseases

Sally Byers

Monash University - Department of Infectious Diseases

Gnei Z. Badoordeen

Monash University - Department of Infectious Diseases

Stephanie Pereira

Monash University - Department of Infectious Diseases

Katherine Pragastis

Monash University - Department of Infectious Diseases

Jason A. Trubiano

Monash University - Department of Infectious Diseases

Kyra Y. L. Chua

Austin Health - Department of Infectious Diseases

Marion Kainer

Western Health - Department of Infectious Diseases

James S. Molton

Western Health - Department of Infectious Diseases

Bradley J. Gardiner

Monash University - Department of Infectious Diseases

Anna Pierce

Monash University - Department of Infectious Diseases

Cheng AC

Monash University - Department of Infectious Diseases

Benjamin A. Rogers

Monash University - Department of Infectious Diseases

Anton Y. Peleg

Monash University - Department of Infectious Diseases

More...

Abstract

Background: 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 in vitro with evidence of clinical benefit in open label trials. Placebo controlled studies of people with early symptomatic COVID-19 with regular assessments of SARS-CoV-2 viral load can determine if it has an antiviral effect and improves clinical outcomes.

Methods: 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: 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 p=0.6 comparing Kaplan Meier curves), progression to hospitalisation (14 favipiravir, 9 placebo; p=0.38), time to symptom resolution (cough, fever, sore throat) and there were no deaths. 51 people related an adverse event that was possibly drug related, but these were evenly distributed (n=24 favipiravir, n=27 placebo). Sensitivity analyses where the definition of virological cure was changed to: a single negative PCR, exclude datapoints based on the presence or absence of human DNA in the swab, a SARS-CoV-2 viral load < 300 copies/mL being considered negative all demonstrated no difference between arms.

Interpretation: 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.

Trial Registration Details: This trial was registered under (NCT04445467).

Funding Information: The study was supported in part by grants from the Commonwealth Bank and the Lord Mayor’s Charitable Foundation. JHM is supported by the Medical Research Future Fund, AYP, JT are supported by the Australian National Health and Medical Research Council.

Declaration of Interests: None to declare.

Ethics Approval Statement: The study was approved by the Alfred Ethics Committee (No 406/20) and all participants provided informed consent.

Keywords: Favipiravir, COVID-19, randomised clinical trial

Suggested Citation

McMahon, James H. and Lau, Jillian S.Y. and Coldham, Anna and Roney, Janine and Hagenauer, Michelle and Price, Sally and Bryant, Mellissa and Garlick, Jill and Paterson, Anne and Lee, Sue J. and O’Bryan, Jess and Hearps, Anna and Tachedjian, Gilda and Pinskier, Henry and Phillips, Cameron and Garrow, Stuart and Pinskier, Nathan and Melvin, Robert and Blakeway, Luke and Wisniewski, Jessica A. and Byers, Sally and Badoordeen, Gnei Z. and Pereira, Stephanie and Pragastis, Katherine and Trubiano, Jason A. and Chua, Kyra Y. L. and Kainer, Marion and Molton, James S. and Gardiner, Bradley J. and Pierce, Anna and AC, Cheng and Rogers, Benjamin A. and Peleg, Anton Y., Favipiravir in Early Symptomatic COVID-19, A Randomised Placebo-Controlled Trial. Available at SSRN: https://ssrn.com/abstract=4135325 or http://dx.doi.org/10.2139/ssrn.4135325

James H. McMahon (Contact Author)

Monash University - Department of Infectious Diseases ( email )

Jillian S.Y. Lau

Monash University - Department of Infectious Diseases ( email )

Anna Coldham

Monash University - Department of Infectious Diseases ( email )

Janine Roney

Monash University - Department of Infectious Diseases ( email )

Michelle Hagenauer

Monash University - Department of Infectious Diseases ( email )

Sally Price

Monash University - Department of Infectious Diseases ( email )

Mellissa Bryant

Monash University - Department of Infectious Diseases ( email )

Jill Garlick

Monash University - Department of Infectious Diseases ( email )

Anne Paterson

Monash University - Department of Infectious Diseases ( email )

Sue J. Lee

Monash University - Department of Infectious Diseases ( email )

Jess O’Bryan

Monash University - Department of Infectious Diseases ( email )

Anna Hearps

Burnet Institute - Life Sciences Discipline ( email )

Australia

Gilda Tachedjian

Burnet Institute - Life Sciences Discipline ( email )

Australia

Henry Pinskier

Onsite Doctor and OSD.Care ( email )

Australia

Cameron Phillips

Onsite Doctor and OSD.Care ( email )

Stuart Garrow

Onsite Doctor and OSD.Care ( email )

Nathan Pinskier

Onsite Doctor and OSD.Care ( email )

Robert Melvin

Onsite Doctor and OSD.Care ( email )

Luke Blakeway

Monash University - Department of Infectious Diseases ( email )

Jessica A. Wisniewski

Monash University - Department of Infectious Diseases ( email )

Sally Byers

Monash University - Department of Infectious Diseases ( email )

Gnei Z. Badoordeen

Monash University - Department of Infectious Diseases ( email )

Stephanie Pereira

Monash University - Department of Infectious Diseases ( email )

Katherine Pragastis

Monash University - Department of Infectious Diseases ( email )

Jason A. Trubiano

Monash University - Department of Infectious Diseases

Kyra Y. L. Chua

Austin Health - Department of Infectious Diseases ( email )

Marion Kainer

Western Health - Department of Infectious Diseases ( email )

Australia

James S. Molton

Western Health - Department of Infectious Diseases ( email )

Australia

Bradley J. Gardiner

Monash University - Department of Infectious Diseases ( email )

Anna Pierce

Monash University - Department of Infectious Diseases ( email )

Cheng AC

Monash University - Department of Infectious Diseases ( email )

Benjamin A. Rogers

Monash University - Department of Infectious Diseases ( email )

Anton Y. Peleg

Monash University - Department of Infectious Diseases ( email )

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