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Molnupiravir Treatment for COVID-19 in People at Higher Risk in the Community: Outcomes from the PANORAMIC Randomised Controlled Trial at Three and Six Months

38 Pages Posted: 7 May 2024

See all articles by Victoria Harris

Victoria Harris

University of Oxford - Nuffield Department of Primary Care Health Sciences

Jane Holmes

University of Oxford - Nuffield Department of Primary Care Health Sciences

Oghenekome Gbinigie

University of Oxford - Nuffield Department of Primary Care Health Sciences

Najib M. Rahman

University of Oxford - Oxford Respiratory Trials Unit; University of Oxford - NIHR Biomedical Research Unit Oxford; University of Oxford - Chinese Academy of Medical Science Oxford Institute (COI)

Duncan Richards

University of Oxford - Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS)

Gail Hayward

University of Oxford - Nuffield Department of Primary Care Health Sciences

Jienchi Dorward

University of Oxford - Nuffield Department of Primary Care Health Sciences; University of KwaZulu-Natal - Centre for the AIDS Programme of Research in South Africa (CAPRISA)

David Lowe

University College London - UCL Institute of Immunity and Transplantation

Joseph Standing

University College London

Judith Breuer

University College London - Department of Infection, Inflammation and Immunity

Saye Khoo

University of Liverpool

Stavros Petrou

University of Oxford - Nuffield Department of Primary Care Health Sciences

Kerenza Hood

Cardiff University

Haroon Ahmed

Cardiff University

Andrew Carson-Stevens

Cardiff University - Centre for Trials Research

Jonathan Nguyen-Van-Tam

University of Nottingham

Mahendra Patel

University of Oxford - Nuffield Department of Primary Care Health Sciences

Benjamin Saville

Berry Consultants, LLC

Nick Francis

University of Southampton - Primary Care Research Centre

Nicholas BP Thomas

Windrush Medical Practice

Philip Evans

University of Exeter - Faculty of Health and Life Sciences; National Institute for Health and Care Research

Melissa Dobson

University of Oxford - Oxford Respiratory Trials Unit

May Ee Png

University of Oxford - Nuffield Department of Primary Care Health Sciences

Mark Lown

University of Southampton - Primary Care Research Centre

Oliver van Hecke

University of Oxford - Nuffield Department of Primary Care Health Sciences

Bhautesh Jani

University of Glasgow - Institute of Health and Wellbeing

Nigel Hart

Queen's University Belfast - School of Medicine, Dentistry & Biomedical Science

Daniel Butler

Queen's University Belfast - School of Medicine, Dentistry & Biomedical Science

Lucy Cureton

University of Oxford - Nuffield Department of Primary Care Health Sciences

Meena Patil

University of Oxford - Nuffield Department of Primary Care Health Sciences

Monique Andersson

Government of the United Kingdom - Oxford University Hospitals NHS Foundation Trust

Maria Coates

University of Oxford - Nuffield Department of Primary Care Health Sciences

Sarah Williams

University of Oxford - Nuffield Department of Primary Care Health Sciences

Clare Bateman

University of Oxford - Nuffield Department of Primary Care Health Sciences

Jennifer Davies

University of Oxford - Nuffield Department of Primary Care Health Sciences

Ivy Raymundo-Wood

University of Oxford - Nuffield Department of Primary Care Health Sciences

Andrew Ustianowski

North Manchester General Hospital - Regional Infectious Diseases Unit

Ly-Mee Yu

University of Oxford - Nuffield Department of Primary Care Health Sciences

Richard Hobbs

University of Oxford - Nuffield Department of Primary Care Health Sciences

Paul Little

University of Southampton

Christopher Butler

University of Oxford - Nuffield Department of Primary Care Health Sciences

PANORAMIC Trial Collaborative Group

Independent

More...

Abstract

Objectives: Treating COVID-19 infection with antiviral drugs may reduce the longer-term impact of the illness, but no randomised controlled trials have yet reported on the effectiveness of molnupiravir on longer term outcomes. The main objective of the current research is to investigate the effects of molnupiravir for COVID-19 at 3- and 6-months post-randomisation.

Design: Participants in this open-label controlled trial were followed up at 3- and 6-months. Bayesian analyses were used to estimate the probability of superiority (odds ratio <1 for dichotomous outcomes).

Setting: Primary healthcare.

Participants: Participants were aged ≥50, or ≥18 years with comorbidities, and unwell ≤5 days with confirmed COVID-19 in the community.

Interventions: Participants were randomised to usual care or usual care plus molnupiravir (800mg twice daily for 5 days).

Main Outcome Measures: Participant ratings of wellness, experiencing any severe or persistent symptom, health and social care use, health-related quality of life (measured by the EQ-5D-5L), time off work, and hospitalisation.

Results: Between December 8, 2021, and April 27, 2022, 25,784 participants were randomised to molnupiravir plus usual care (n=12,821) or usual care alone (n=12,963). Long-term follow-up data were available for 23,008 (89.2%), and 99.1% had at least one prior dose of a SARS-CoV-2 vaccine. A range of symptoms were reduced in severity and health-related quality of life (measured by the EQ-5D-5L) improved in the molnupiravir group at 3- and 6- months. Ratings of wellness, experiencing any severe symptom, and health care use had high probabilities of superiority with molnupiravir treatment, but low probability of being clinically meaningful. There were statistically significant differences in persistence of any symptom (8.5% vs 11%, Number Needed to Treat (NNT) = 67)) at 6 months, and reported time off work at 3 months (17‧9% vs 22 ‧4%)  and 6 months (4‧4% vs 5‧4%; NNT= 100). There remained no difference in hospitalisations at long term follow-up.  
Conclusions: Molnupiravir for acute COVID-19 helped patients feel better, experience fewer and less severe COVID-19 associated symptoms, access health care less often, and take less time off work at 6-months. However, the absolute differences are small with potentially high estimated numbers needed to treat.

Trial Registration: ISRCTN30448031.

Funding: National Institute of Health and Care ResearchNIHR135366.

Declaration of Interest: JSN-V-T was seconded to the Department of Health and Social Care, England (DHSC) from October 2017 to March 2022. The views expressed in this paper are those of its authors and not necessarily those of DHSC or its agencies. In Spring 2023, he completed one, 3-hour, paid consultancy assignment for MSD on a subject unrelated to COVID-19. He has given two paid lectures for Gilead who also manufacture COVID-19 treatments in 2022-23, and one paid lecture for AstraZeneca in 2022, who manufacture COVID-19 vaccines. He consults occasionally for Moderna (2023 onwards) who manufacture COVID-19 vaccines. D.M.L has received personal fees from Gilead for an educational video and from Merck for a roundtable discussion, speaker fees from Biotest, Takeda and Astra-Zeneca and support to attend a conference from Octapharma. D.M.L. also holds research grants from GSK and Bristol Myers Squibb and has received consultancy fees from GSK paid to his institution, all outside the current work.

Ethical Approval: The UK Medicines and Healthcare products Regulatory Agency and the South Central- Berkshire Research Ethics Committee approved the trial protocol. Online informed consent was obtained from all participants. Patients were not involved in the design, or conduct, or reporting, or dissemination plans of our research. The authors vouch for the accuracy and completeness of the data and for fidelity to the protocol. An independent Trial Steering Committee (TSC) and Data Monitoring and Safety Committee (DMSC) provide trial oversight.

Keywords: SARS-CoV-2, Primary Care, COVID-19, Randomized controlled trial, Long term follow-up

Suggested Citation

Harris, Victoria and Holmes, Jane and Gbinigie, Oghenekome and Rahman, Najib M. and Richards, Duncan and Hayward, Gail and Dorward, Jienchi and Lowe, David and Standing, Joseph and Breuer, Judith and Khoo, Saye and Petrou, Stavros and Hood, Kerenza and Ahmed, Haroon and Carson-Stevens, Andrew and Nguyen-Van-Tam, Jonathan and Patel, Mahendra and Saville, Benjamin and Francis, Nick and Thomas, Nicholas BP and Evans, Philip and Dobson, Melissa and Png, May Ee and Lown, Mark and van Hecke, Oliver and Jani, Bhautesh and Hart, Nigel and Butler, Daniel and Cureton, Lucy and Patil, Meena and Andersson, Monique and Coates, Maria and Williams, Sarah and Bateman, Clare and Davies, Jennifer and Raymundo-Wood, Ivy and Ustianowski, Andrew and Yu, Ly-Mee and Hobbs, F.D. Richard and Little, Paul and Butler, Christopher and Group, PANORAMIC Trial Collaborative, Molnupiravir Treatment for COVID-19 in People at Higher Risk in the Community: Outcomes from the PANORAMIC Randomised Controlled Trial at Three and Six Months. Available at SSRN: https://ssrn.com/abstract=4816081 or http://dx.doi.org/10.2139/ssrn.4816081

Victoria Harris

University of Oxford - Nuffield Department of Primary Care Health Sciences ( email )

Oxford
United Kingdom

Jane Holmes

University of Oxford - Nuffield Department of Primary Care Health Sciences ( email )

Oxford
United Kingdom

Oghenekome Gbinigie

University of Oxford - Nuffield Department of Primary Care Health Sciences ( email )

Oxford
United Kingdom

Najib M. Rahman

University of Oxford - Oxford Respiratory Trials Unit ( email )

Mansfield Road
Oxford, Oxfordshire OX1 4AU
United Kingdom

University of Oxford - NIHR Biomedical Research Unit Oxford ( email )

Oxford
United Kingdom

University of Oxford - Chinese Academy of Medical Science Oxford Institute (COI) ( email )

United Kingdom

Duncan Richards

University of Oxford - Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS) ( email )

Oxford
United Kingdom

Gail Hayward

University of Oxford - Nuffield Department of Primary Care Health Sciences ( email )

Oxford
United Kingdom

Jienchi Dorward

University of Oxford - Nuffield Department of Primary Care Health Sciences ( email )

Oxford
United Kingdom

University of KwaZulu-Natal - Centre for the AIDS Programme of Research in South Africa (CAPRISA) ( email )

2nd Floor, Doris Duke Medical Research Institute
719 Umbilo Road
Durban, 4041
South Africa

David Lowe

University College London - UCL Institute of Immunity and Transplantation ( email )

Gower Street
London, WC1E 6BT
United Kingdom

Joseph Standing

University College London ( email )

Gower Street
London, WC1E 6BT
United Kingdom

Judith Breuer

University College London - Department of Infection, Inflammation and Immunity ( email )

30 Guilford Street
London
United Kingdom

Saye Khoo

University of Liverpool ( email )

Chatham Street
Brownlow Hill
Liverpool, L69 7ZA
United Kingdom

Stavros Petrou

University of Oxford - Nuffield Department of Primary Care Health Sciences ( email )

Oxford
United Kingdom

Kerenza Hood

Cardiff University ( email )

Haroon Ahmed

Cardiff University ( email )

Aberconway Building
Colum Drive
Cardiff, CF10 3EU
United Kingdom

Andrew Carson-Stevens

Cardiff University - Centre for Trials Research ( email )

Cardiff
United Kingdom

Jonathan Nguyen-Van-Tam

University of Nottingham ( email )

University Park
Nottingham, NG8 1BB
United Kingdom

Mahendra Patel

University of Oxford - Nuffield Department of Primary Care Health Sciences ( email )

Oxford
United Kingdom

Benjamin Saville

Berry Consultants, LLC ( email )

Nick Francis

University of Southampton - Primary Care Research Centre ( email )

United Kingdom

Nicholas BP Thomas

Windrush Medical Practice ( email )

Philip Evans

University of Exeter - Faculty of Health and Life Sciences ( email )

United Kingdom

National Institute for Health and Care Research ( email )

United Kingdom

Melissa Dobson

University of Oxford - Oxford Respiratory Trials Unit ( email )

Mansfield Road
Oxford, Oxfordshire OX1 4AU
United Kingdom

May Ee Png

University of Oxford - Nuffield Department of Primary Care Health Sciences ( email )

Oxford
United Kingdom

Mark Lown

University of Southampton - Primary Care Research Centre ( email )

United Kingdom

Oliver Van Hecke

University of Oxford - Nuffield Department of Primary Care Health Sciences ( email )

Oxford
United Kingdom

Bhautesh Jani

University of Glasgow - Institute of Health and Wellbeing ( email )

Glasgow
United Kingdom

Nigel Hart

Queen's University Belfast - School of Medicine, Dentistry & Biomedical Science ( email )

Belfast
Ireland

Daniel Butler

Queen's University Belfast - School of Medicine, Dentistry & Biomedical Science ( email )

Belfast
Ireland

Lucy Cureton

University of Oxford - Nuffield Department of Primary Care Health Sciences ( email )

Oxford
United Kingdom

Meena Patil

University of Oxford - Nuffield Department of Primary Care Health Sciences ( email )

Oxford
United Kingdom

Monique Andersson

Government of the United Kingdom - Oxford University Hospitals NHS Foundation Trust ( email )

Headley Way
Headington
Oxford, OX3 9DU
United Kingdom

Maria Coates

University of Oxford - Nuffield Department of Primary Care Health Sciences ( email )

Oxford
United Kingdom

Sarah Williams

University of Oxford - Nuffield Department of Primary Care Health Sciences ( email )

Oxford
United Kingdom

Clare Bateman

University of Oxford - Nuffield Department of Primary Care Health Sciences ( email )

Oxford
United Kingdom

Jennifer Davies

University of Oxford - Nuffield Department of Primary Care Health Sciences ( email )

Oxford
United Kingdom

Ivy Raymundo-Wood

University of Oxford - Nuffield Department of Primary Care Health Sciences ( email )

Oxford
United Kingdom

Andrew Ustianowski

North Manchester General Hospital - Regional Infectious Diseases Unit ( email )

Manchester
United Kingdom

Ly-Mee Yu

University of Oxford - Nuffield Department of Primary Care Health Sciences ( email )

Oxford
United Kingdom

F.D. Richard Hobbs

University of Oxford - Nuffield Department of Primary Care Health Sciences ( email )

Oxford
United Kingdom

Paul Little

University of Southampton ( email )

Southampton Business School
Southampton
United Kingdom

Christopher Butler (Contact Author)

University of Oxford - Nuffield Department of Primary Care Health Sciences ( email )

Oxford
United Kingdom

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