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Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial

Butler, Christopher C; Hobbs, F D Richard; Gbinigie, Oghenekome A; Rahman, Najib M; Hayward, Gail; Richards, Duncan B; Dorward, Jienchi; Lowe, David M; Standing, Joseph F; Breuer, Judith; Khoo, Saye; Petrou, Stavros; Hood, Kerenza; Nguyen-Van-Tam, Jonathan S; Patel, Mahendra G; Saville, Benjamin R; Marion, Joe; Ogburn, Emma; Allen, Julie; Rutter, Heather; Francis, Nick; Thomas, Nicholas P B; Evans, Philip; Dobson, Melissa; Madden, Tracie-Ann; Holmes, Jane; Harris, Victoria; Png, May Ee; Lown, Mark; van Hecke, Oliver; Detry, Michelle A; Saunders, Christina T; Fitzgerald, Mark; Berry, Nicholas S; Mwandigha, Lazaro; Galal, Ushma; Mort, Sam; Jani, Bhautesh D; Hart, Nigel D; Ahmed, Haroon; Butler, Daniel; McKenna, Micheal; Chalk, Jem; Lavallee, Layla; Hadley, Elizabeth; Cureton, Lucy; Benysek, Magdalena; Andersson, Monique; Coates, Maria; Barrett, Sarah; Bateman, Clare; Davies, Jennifer C; Raymundo-Wood, Ivy; Ustianowski, Andrew; Carson-Stevens, Andrew; Yu, Ly-Mee; Little, Paul; Agyeman, Ak...

Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial Thumbnail


Christopher C Butler

F D Richard Hobbs

Oghenekome A Gbinigie

Najib M Rahman

Gail Hayward

Duncan B Richards

Jienchi Dorward

David M Lowe

Joseph F Standing

Judith Breuer

Saye Khoo

Stavros Petrou

Kerenza Hood

Mahendra G Patel

Benjamin R Saville

Joe Marion

Emma Ogburn

Julie Allen

Heather Rutter

Nick Francis

Nicholas P B Thomas

Philip Evans

Melissa Dobson

Tracie-Ann Madden

Jane Holmes

Victoria Harris

May Ee Png

Mark Lown

Oliver van Hecke

Michelle A Detry

Christina T Saunders

Mark Fitzgerald

Nicholas S Berry

Lazaro Mwandigha

Ushma Galal

Sam Mort

Bhautesh D Jani

Nigel D Hart

Haroon Ahmed

Daniel Butler

Micheal McKenna

Jem Chalk

Layla Lavallee

Elizabeth Hadley

Lucy Cureton

Magdalena Benysek

Monique Andersson

Maria Coates

Sarah Barrett

Clare Bateman

Jennifer C Davies

Ivy Raymundo-Wood

Andrew Ustianowski

Andrew Carson-Stevens

Ly-Mee Yu

Paul Little

Akosua A Agyeman

Tanveer Ahmed

Damien Allcock

Adrian Beltran-Martinez

Oluseye E Benedict

Nigel Bird

Laura Brennan

Julianne Brown

Gerard Burns

Mike Butler

Zelda Cheng

Ruth Danson

Nigel de Kare-Silver

Devesh Dhasmana

Jon Dickson

Serge Engamba

Stacey Fisher

Robin Fox

Eve Frost

Richard Gaunt

Sarit Ghosh

Ishtiaq Gilkar

Anna Goodman

Steve Granier

Aleksandra Howell

Iqbal Hussain

Simon Hutchinson

Marie Imlach

Greg Irving

Nicholas Jacobsen

James Kennard

Umar Khan

Kyle Knox

Christopher Krasucki

Tom Law

Rem Lee

Nicola Lester

David Lewis

James Lunn

Claire I. Mackintosh

Mehul Mathukia

Patrick Moore

Seb Morton

Daniel Murphy

Rhiannon Nally

Chinonso Ndukauba

Olufunto Ogundapo

Henry Okeke

Amit Patel

Kavil Patel

Ruth Penfold

Satveer Poonian

Olajide Popoola

Alexander Pora

Vibhore Prasad

Rishabh Prasad

Omair Razzaq

Scot Richardson

Simon Royal

Afsana Safa

Satash Sehdev

Tamsin Sevenoaks

Divya Shah

Aadil Sheikh

Vanessa Short

Baljinder S Sidhu

Ivor Singh

Yusuf Soni

Chris Thalasselis

Pete Wilson

David Wingfield

Michael Wong

Maximillian N J Woodall

Nick Wooding

Sharon Woods

Joanna Yong

Francis Yongblah

Azhar Zafar


Background: The safety, effectiveness, and cost-effectiveness of molnupiravir, an oral antiviral medication for SARS-CoV-2, has not been established in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19. We aimed to establish whether the addition of molnupiravir to usual care reduced hospital admissions and deaths associated with COVID-19 in this population. Methods: PANORAMIC was a UK-based, national, multicentre, open-label, multigroup, prospective, platform adaptive randomised controlled trial. Eligible participants were aged 50 years or older—or aged 18 years or older with relevant comorbidities—and had been unwell with confirmed COVID-19 for 5 days or fewer in the community. Participants were randomly assigned (1:1) to receive 800 mg molnupiravir twice daily for 5 days plus usual care or usual care only. A secure, web-based system (Spinnaker) was used for randomisation, which was stratified by age (<50 years vs ≥50 years) and vaccination status (yes vs no). COVID-19 outcomes were tracked via a self-completed online daily diary for 28 days after randomisation. The primary outcome was all-cause hospitalisation or death within 28 days of randomisation, which was analysed using Bayesian models in all eligible participants who were randomly assigned. This trial is registered with ISRCTN, number 30448031. Findings: Between Dec 8, 2021, and April 27, 2022, 26 411 participants were randomly assigned, 12 821 to molnupiravir plus usual care, 12 962 to usual care alone, and 628 to other treatment groups (which will be reported separately). 12 529 participants from the molnupiravir plus usual care group, and 12 525 from the usual care group were included in the primary analysis population. The mean age of the population was 56·6 years (SD 12·6), and 24 290 (94%) of 25 708 participants had had at least three doses of a SARS-CoV-2 vaccine. Hospitalisations or deaths were recorded in 105 (1%) of 12 529 participants in the molnupiravir plus usual care group versus 98 (1%) of 12 525 in the usual care group (adjusted odds ratio 1·06 [95% Bayesian credible interval 0·81–1·41]; probability of superiority 0·33). There was no evidence of treatment interaction between subgroups. Serious adverse events were recorded for 50 (0·4%) of 12 774 participants in the molnupiravir plus usual care group and for 45 (0·3%) of 12 934 in the usual care group. None of these events were judged to be related to molnupiravir. Interpretation: Molnupiravir did not reduce the frequency of COVID-19-associated hospitalisations or death among high-risk vaccinated adults in the community. Funding: UK National Institute for Health and Care Research


Butler, C. C., Hobbs, F. D. R., Gbinigie, O. A., Rahman, N. M., Hayward, G., Richards, D. B., …Zafar, A. (2023). Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial. Lancet, 401(10373), 281-293.

Journal Article Type Article
Acceptance Date Nov 29, 2022
Online Publication Date Dec 22, 2022
Publication Date Jan 28, 2023
Deposit Date Jan 5, 2023
Publicly Available Date Jan 5, 2023
Journal The Lancet
Print ISSN 0140-6736
Electronic ISSN 1474-547X
Publisher Elsevier BV
Peer Reviewed Peer Reviewed
Volume 401
Issue 10373
Pages 281-293
Keywords General Medicine
Public URL
Publisher URL
Additional Information User license: Creative Commons Attribution (CC BY 4.0)