Platform adaptive trial of novel antivirals for early treatment of COVID-19 In the community (PANORAMIC): protocol for a randomised, controlled, open-label, adaptive platform trial of community novel antiviral treatment of COVID-19 in people at increased risk of more severe disease
Najib Rahman,
Andrew Carson-Stevens,
Stavros Petrou,
Judith Breuer,
Paul Little,
Melissa Dobson,
Kerenza Hood,
Jienchi Dorward,
May Ee Png,
Richard Hobbs,
Gail Hayward,
Mark Lown,
Nigel Hart,
Ly-Mee Yu,
Nick Francis,
Oliver van Hecke,
Julie Allen,
Joseph F Standing,
Emma Ogburn,
Jennifer Davies,
Christopher C Butler,
Saye Khoo,
Andrew Ustianowski,
Victoria Harris,
Bhautesh Jani,
Jane Holmes,
Heather Rutter,
Oghenekome Gbinigie,
Lucy Cureton,
Sarah Barrett,
Benjamin R Saville,
Monique I Andersson,
Mahendra Patel,
Jonathan Nguyen-Van-Tam,
Duncan Richards,
Layla Lavallee,
David M Lowe,
Tracie-Ann Madden,
Joe Marion,
Jem Chalk,
Elizabeth Hadley,
Magdalena Benysek,
Mona Koshkouei,
Maria Coates,
Clare Bateman,
Ivy Raymundo-Wood
Affiliations
Najib Rahman
Oxford Respiratory Trials Unit, University of Oxford, Oxford, UK
Andrew Carson-Stevens
1 Division of Population Medicine, School of Medicine, Cardiff University, Cardiff, UK
Stavros Petrou
Nuffield Department of Primary Care and Health Science, Oxford University, Oxford, UK
Judith Breuer
Institute of Child Health, University College London, London, UK
Paul Little
Primary Care Research Centre, University of Southampton Faculty of Medicine, Southampton, UK
Melissa Dobson
Oxford Respiratory Trials Unit, University of Oxford, Oxford, UK
Kerenza Hood
10 Centre for Trials Research, Cardiff University, Cardiff, UK
Jienchi Dorward
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
May Ee Png
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
Richard Hobbs
University of Oxford, Oxford, UK
Gail Hayward
4 Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
Mark Lown
15 School of Primary Care, Population Sciences and Medical Education, University of Southampton, Southampton, UK
Nigel Hart
School of Medicine, Dentistry and Biomedical Sciences - Centre for Public Health, Queen`s University Belfast, Belfast, UK
Ly-Mee Yu
senior medical statistician
Nick Francis
2 Primary Care Research Centre, School of Primary Care, Population Sciences and Medical Education, University of Southampton, Southampton, UK
Oliver van Hecke
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
Julie Allen
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
Joseph F Standing
Infection Inflammation and Immunology, UCL Great Ormond Street Institute of Child Health Population Policy and Practice, London, UK
Emma Ogburn
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
Jennifer Davies
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
Christopher C Butler
Nuffield Department of Primary Care Health Sciences, Clinical Trials Unit, University of Oxford, Oxford, UK
Saye Khoo
Department of Pharmacology, University of Liverpool, Liverpool, UK
Andrew Ustianowski
NIHR Clinical Research Network: Greater Manchester, Manchester University NHS Foundation Trust, Manchester, UK
Victoria Harris
University of Leicester, Leicester, UK
Bhautesh Jani
General Practice and Primary Care, University of Glasgow, Glasgow, UK
Jane Holmes
senior medical statistician
Heather Rutter
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
Oghenekome Gbinigie
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
Lucy Cureton
5 NDORMS, University of Oxford, Oxford, UK
Sarah Barrett
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
Benjamin R Saville
Berry Consultants, Austin, Texas, USA
Monique I Andersson
Department of Microbiology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
Mahendra Patel
head
Jonathan Nguyen-Van-Tam
2University of Nottingham, Epidemiology and Public Health, Nottingham, United Kingdom
Duncan Richards
Oxford Clinical Trials Research Unit, Botnar Research Centre, University of Oxford, Oxford, UK
Layla Lavallee
Nuffield Department of Primary Care Health Sciences, University of Oxford Medical Sciences Division, Oxford, UK
David M Lowe
Institute for Immunity and Transplantation, Divison of Infection and Immunity, University College London, London, UK
Tracie-Ann Madden
Centre for Trials Research, Cardiff University, Cardiff, UK
Joe Marion
Berry Consultants, Austin, Texas, USA
Jem Chalk
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
Elizabeth Hadley
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
Magdalena Benysek
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
Mona Koshkouei
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
Maria Coates
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
Clare Bateman
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
Ivy Raymundo-Wood
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
Introduction There is an urgent need to determine the safety, effectiveness and cost-effectiveness of novel antiviral treatments for COVID-19 in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19.Methods and analysis PANORAMIC is a UK-wide, open-label, prospective, adaptive, multiarm platform, randomised clinical trial that evaluates antiviral treatments for COVID-19 in the community. A master protocol governs the addition of new antiviral treatments as they become available, and the introduction and cessation of existing interventions via interim analyses. The first two interventions to be evaluated are molnupiravir (Lagevrio) and nirmatrelvir/ritonavir (Paxlovid). Eligibility criteria: community-dwelling within 5 days of onset of symptomatic COVID-19 (confirmed by PCR or lateral flow test), and either (1) aged 50 years and over, or (2) aged 18–49 years with qualifying comorbidities. Registration occurs via the trial website and by telephone. Recruitment occurs remotely through the central trial team, or in person through clinical sites. Participants are randomised to receive either usual care or a trial drug plus usual care. Outcomes are collected via a participant-completed daily electronic symptom diary for 28 days post randomisation. Participants and/or their Trial Partner are contacted by the research team after days 7, 14 and 28 if the diary is not completed, or if the participant is unable to access the diary. The primary efficacy endpoint is all-cause, non-elective hospitalisation and/or death within 28 days of randomisation. Multiple prespecified interim analyses allow interventions to be stopped for futility or superiority based on prespecified decision criteria. A prospective economic evaluation is embedded within the trial.Ethics and dissemination Ethical approval granted by South Central–Berkshire REC number: 21/SC/0393; IRAS project ID: 1004274. Results will be presented to policymakers and at conferences, and published in peer-reviewed journals.Trial registration number ISRCTN30448031; EudraCT number: 2021-005748-31.
