ASCOT ADAPT study of COVID-19 therapeutics in hospitalised patients: an international multicentre adaptive platform trial
Justin T. Denholm,
Balasubramanian Venkatesh,
Joshua Davis,
Asha C. Bowen,
Naomi E. Hammond,
Vivekanand Jha,
Grace McPhee,
Zoe McQuilten,
Matthew V. N. O’Sullivan,
David Paterson,
David Price,
Megan Rees,
Jason Roberts,
Mark Jones,
James Totterdell,
Thomas Snelling,
Nanette Trask,
Susan Morpeth,
Steven YC Tong,
on behalf of the ASCOT ADAPT investigators
Affiliations
Justin T. Denholm
Victorian Infectious Diseases Service, The Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity
Balasubramanian Venkatesh
The George Institute for Global Health
Joshua Davis
Menzies School of Health Research, Charles Darwin University
Asha C. Bowen
Menzies School of Health Research, Charles Darwin University
Naomi E. Hammond
The George Institute for Global Health
Vivekanand Jha
The George Institute for Global Health
Grace McPhee
Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity
Zoe McQuilten
Australian and New Zealand Intensive Care Research Centre (ANZIC-RC), Monash University
Matthew V. N. O’Sullivan
Department of Infectious Diseases Westmead Hospital
David Paterson
University of Queensland Centre for Clinical Research, Faculty of Medicine & Centre for Translational Anti-infective Pharmacodynamics, School of Pharmacy, The University of Queensland
David Price
Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity
Megan Rees
Department of Respiratory Medicine, The Royal Melbourne Hospital and Department of Medicine, University of Melbourne
Jason Roberts
University of Queensland Centre for Clinical Research, Faculty of Medicine & Centre for Translational Anti-infective Pharmacodynamics, School of Pharmacy, The University of Queensland
Mark Jones
School of Public Health, University of Sydney
James Totterdell
School of Public Health, University of Sydney
Thomas Snelling
Department of Infectious Diseases, John Hunter Hospital
Nanette Trask
Susan Morpeth
Middlemore Hospital, Counties Manukau District Health Board
Steven YC Tong
Victorian Infectious Diseases Service, The Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity
Abstract Background SARS-CoV-2 infection is associated with a significant risk of hospitalisation, death, and prolonged impact on quality of life. Evaluation of new treatment options and optimising therapeutic management of people hospitalised with SARS-CoV-2 infection remains essential, but rapid changes in pandemic conditions and potential therapies have limited the utility of traditional approaches to randomised controlled trials. Methods ASCOT ADAPT is an international, investigator-initiated, adaptive platform, randomised controlled trial of therapeutics for non-critically ill patients hospitalised with COVID-19. The study design is open label and pragmatic. Potential participants are hospitalised adults with PCR confirmed, symptomatic, SARS-CoV-2 infection, within 14 days of symptom onset. Domains include antiviral, antibody and anticoagulant interventions, with a composite primary outcome of 28-day mortality or progression to intensive-care level respiratory or haemodynamic support. Initial interventions include intravenous nafamostat and variable dose anticoagulation. A range of secondary endpoints, and substudies for specific domains and interventions are outlined. Discussion This paper presents the trial protocol and management structure, including international governance, remote site monitoring and biobanking activities and provides commentary on ethical and pragmatic considerations in establishing the ASCOT ADAPT trial under pandemic conditions. Trial registration Australian and New Zealand Clinical Trials Registry (ACTRN12620000445976) and ClinicalTrials.gov (NCT04483960).
