Favipiravir for COVID-19 in adults in the community in PRINCIPLE, an open-label, randomised, controlled, adaptive platform trial of short- and longer-term outcomes - 17/09/24

Doi : 10.1016/j.jinf.2024.106248

FD Richard Hobbs ^a,^{^{1
Professor Hobbs, Dr Gbinigie-Thompson and Dr Shanyinde contributed equally.}}, Oghenekome A. Gbinigie-Thompson ^a,^{^{1
Professor Hobbs, Dr Gbinigie-Thompson and Dr Shanyinde contributed equally.}}, Milensu Shanyinde ^a,^{^{1
Professor Hobbs, Dr Gbinigie-Thompson and Dr Shanyinde contributed equally.}}, Ly-Mee Yu ^a, Victoria Harris ^a, Jienchi Dorward ^a,^c, Gail Hayward ^a, Benjamin R. Saville ^d,^e, Nicholas S. Berry ^d, Philip H. Evans ^f,^g, Nicholas PB Thomas ^h,ⁱ, Mahendra G. Patel ^a, Duncan Richards ^j, Oliver Van Hecke ^a, Michelle A. Detry ^d, Christina T. Saunders ^d, Mark Fitzgerald ^d, Jared Robinson ^a, Charlotte Latimer-Bell ^a, Julie Allen ^a, Emma Ogburn ^a, Jenna Grabey ^a, Simon de Lusignan ^a,^h, Monique Andersson ^k, Paul Little ^b,^{^{2
Professors Little and Butler contributed equally.}}, Christopher C. Butler ^a,^⁎,^{^{2
Professors Little and Butler contributed equally.}}
PRINCIPLE Trial Collaborative Group^³
The collaborators of the PRINCIPLE Trial Collaborative Group are listed in the Appendix A.
^a Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
^b Primary Care Research Centre, University of Southampton, UK
^c Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu–Natal, Durban, South Africa
^d Berry Consultants, TX, USA
^e Department of Biostatistics, Vanderbilt University School of Medicine, TN, USA
^f Department of Health and Community Sciences, University of Exeter, Exeter, UK
^g National Institute for Health Research (NIHR) Clinical Research Network, National Institute for Health and Care Research, Leeds, UK
^h Royal College of General Practitioners, London, UK
ⁱ National Institute for Health Research (NIHR) Clinical Research Network Thames Valley and South Midlands, National Institute for Health and Care Research, Oxford, UK
^j Oxford Clinical Trials Research Unit, Botnar Research Centre, University of Oxford, Oxford, UK
^k Department of Microbiology, Oxford University Hospitals NHS Trust, Oxford, UK

^⁎Correspondence to: Nuffield Department of Primary Care Health Sciences, University of Oxford, Gibson Building 1st Floor, Radcliffe Observatory Quarter, Woodstock Road, Oxford OX2 6GG, UK.Nuffield Department of Primary Care Health Sciences, University of OxfordGibson Building 1st Floor, Radcliffe Observatory Quarter, Woodstock RoadOxfordOX2 6GGUK

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Summary

Background

Evidence for the effect of favipiravir treatment of acute COVID-19 on recovery, hospital admissions and longer-term outcomes in community settings is limited.

Methods

In this multicentre. open-label, multi-arm, adaptive platform randomised controlled trial participants aged ≥18 years in the community with a positive test for SARS-CoV-2 and symptoms lasting ≤14 days were randomised to: usual care; usual care plus favipiravir tablets (loading dose of 3600 mg in divided doses on day one, then 800 mg twice a day for four days); or, usual care plus other interventions. Co-primary endpoints were time to first self-reported recovery and hospitalisation/death related to COVID-19, within 28 days, analysed using Bayesian models. Recovery at six months was the primary longer-term outcome. Trial registration: ISRCTN86534580.

Findings

The primary analysis model included 8811 SARS-CoV-2 positive mostly COVID vaccinated participants, randomised to favipiravir (n = 1829), usual care (n = 3256), and other treatments (n = 3726). Time to self-reported recovery was shorter in the favipiravir group than usual care (estimated hazard ratio 1·23 [95% credible interval 1·14 to 1·33]), a reduction of 2·98 days [1·99 to 3·94] from 16 days in median time to self-reported recovery for favipiravir versus usual care alone. COVID-19 related hospitalisations/deaths were similar (estimated odds ratio 0·99 [0·61 to 1·61]; estimated difference 0% [−0·9% to 0·6%]). 14 serious adverse events occurred in the favipiravir group and 4 in usual care. By six months, the proportion feeling fully recovered was 74·9% for favipiravir versus 71·3% for usual care (RR = 1·05, [1·02 to 1·08]).

Interpretation

In this open-label trial in a largely vaccinated population with COVID-19 in the community, favipiravir did not reduce hospital admissions, but shortened time to recovery and had a marginal positive impact on long term outcomes.

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Keywords : SARS-CoV2, COVID-19, Favipiravir, Clinical trial, Long-term follow-up

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Vol 89 - N° 4

Article 106248- octobre 2024 Retour au numéro

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Favipiravir for COVID-19 in adults in the community in PRINCIPLE, an open-label, randomised, controlled, adaptive platform trial of short- and longer-term outcomes - 17/09/24

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