부산대학교 도서관

Summary 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 ( 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 Author Affiliation: (a) Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK (b) Oxford Respiratory Trials Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK (c) Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford, UK (d) Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK (e) Oxford National Institute for Health and Care Research Biomedical Research Centre, Oxford, UK (f) Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu--Natal, Durban, South Africa (g) Institute of Immunity and Transplantation, University College London, London, UK (h) Infection, Inflammation and Immunology, UCL Great Ormond Street Institute of Child Health, London, UK (i) Department of Pharmacy, Great Ormond Street Hospital for Children, London, UK (j) Department of Pharmacology, University of Liverpool, Liverpool, UK (k) Centre for Trials Research, Cardiff University, Cardiff, UK (l) Division of Population Medicine, Cardiff University, Cardiff, UK (m) Lifespan and Population Health Unit, University of Nottingham School of Medicine, Nottingham, UK (n) Berry Consultants, Austin, TX, USA (o) Department of Biostatistics, Vanderbilt School of Medicine, Nashville, TN, USA (p) Primary Care Research Centre, University of Southampton, Southampton, UK (q) Windrush Medical Practice, Witney, UK (r) National Institute for Health and Care Research Clinical Research Network: Thames Valley and South Midlands, Oxford, UK (s) Royal College of General Practitioners, London, UK (t) Faculty of Health and Life Sciences, University of Exeter, Exeter, UK (u) National Institute for Health and Care Research Clinical Research Network, Leeds, UK (v) General Practice and Primary Care, School of Health and Wellbeing, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, UK (w) School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK (x) Department of Microbiology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK (y) and Regional Infectious Diseases Unit, North Manchester General Hospital, Manchester, UK * Correspondence to: Prof Christopher C Butler, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford OX2 6GG, UK (footnote)* These authors contributed equally (footnote)[Dagger] These authors contributed equally (footnote)[double dagger] Members listed at end of paper Byline: Prof Christopher C Butler, FMedSci [christopher.butler@phc.ox.ac.uk] (a), Prof F D Richard Hobbs, FMedSci (a), Oghenekome A Gbinigie, DPhil (a), Prof Najib M Rahman, DPhil (b,c,e), Gail Hayward, DPhil (a), Prof Duncan B Richards, DM (d), Jienchi Dorward, MBChB (a,f), David M Lowe, PhD (g), Prof Joseph F Standing, PhD (h,i), Prof Judith Breuer, MD (h), Prof Saye Khoo, FRCP (j), Prof Stavros Petrou, PhD (a), Prof Kerenza Hood, PhD (k), Prof Jonathan S Nguyen-Van-Tam, FMedSci (m), Prof Mahendra G Patel, PhD (a), Benjamin R Saville, PhD (n,o), Joe Marion, PhD (n), Emma Ogburn (a), Julie Allen, BA (a), Heather Rutter, BSc (a), Prof Nick Francis, PhD (p), Nicholas P B Thomas, FRCGP (q,r,s), Prof Philip Evans, FRCGP (t,u), Melissa Dobson, BSc (b), Tracie-Ann Madden, PhD (k), Jane Holmes, PhD (a), Victoria Harris, PhD (a), May Ee Png, PhD (a), Mark Lown, PhD (p), Oliver van Hecke, DPhil (a), Michelle A Detry, PhD (n), Christina T Saunders, PhD (n), Mark Fitzgerald, PhD (n), Nicholas S Berry, PhD (n), Lazaro Mwandigha, PhD (a), Ushma Galal, MSc (a), Sam Mort, PGCert (a), Bhautesh D Jani, PhD (v), Prof Nigel D Hart, MD (w), Haroon Ahmed, PhD (l), Daniel Butler, MBChB (w), Micheal McKenna, BSc (a), Jem Chalk, PhD (a), Layla Lavallee, MPH (a), Elizabeth Hadley, MSc (a), Lucy Cureton, BSc (a), Magdalena Benysek, MSc (a), Monique Andersson, MD (x), Maria Coates (a), Sarah Barrett (a), Clare Bateman, BA (a), Jennifer C Davies, PhD (a), Ivy Raymundo-Wood, BSc (a), Prof Andrew Ustianowski, PhD (y), Prof Andrew Carson-Stevens, PhD (l), Ly-Mee Yu, DPhil (a,[Dagger]), Prof Paul Little, FMedSci (p,[Dagger]), 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