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).

Details

Title
ASCOT ADAPT study of COVID-19 therapeutics in hospitalised patients: an international multicentre adaptive platform trial
Author
Denholm, Justin T. 1   VIAFID ORCID Logo  ; Venkatesh, Balasubramanian 2 ; Davis, Joshua 3 ; Bowen, Asha C. 4 ; Hammond, Naomi E. 5 ; Jha, Vivekanand 6 ; McPhee, Grace 7 ; McQuilten, Zoe 8 ; O’Sullivan, Matthew V. N. 9 ; Paterson, David 10 ; Price, David 7 ; Rees, Megan 11 ; Roberts, Jason 12 ; Jones, Mark 13 ; Totterdell, James 13 ; Snelling, Thomas 14 ; Trask, Nanette 15 ; Morpeth, Susan 16 ; Tong, Steven YC 1 

1  Victorian Infectious Diseases Service, The Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia (GRID:grid.416153.4) (ISNI:0000 0004 0624 1200); The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Department of Infectious Diseases, Melbourne, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X) 
2  The George Institute for Global Health, Sydney, Australia (GRID:grid.415508.d) (ISNI:0000 0001 1964 6010); The George Institute for Global Health, New Delhi, India (GRID:grid.464831.c) (ISNI:0000 0004 8496 8261); University of New South Wales, Faculty of Medicine, Sydney, Australia (GRID:grid.1005.4) (ISNI:0000 0004 4902 0432) 
3  Charles Darwin University, Menzies School of Health Research, Darwin, Australia (GRID:grid.1043.6) (ISNI:0000 0001 2157 559X); John Hunter Hospital, Department of Infectious Diseases, Newcastle, Australia (GRID:grid.414724.0) (ISNI:0000 0004 0577 6676) 
4  Charles Darwin University, Menzies School of Health Research, Darwin, Australia (GRID:grid.1043.6) (ISNI:0000 0001 2157 559X); Perth Children’s Hospital, Department of Infectious Diseases, Perth, Australia (GRID:grid.410667.2) (ISNI:0000 0004 0625 8600); University of Western Australia, Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Australia (GRID:grid.1012.2) (ISNI:0000 0004 1936 7910) 
5  The George Institute for Global Health, Sydney, Australia (GRID:grid.415508.d) (ISNI:0000 0001 1964 6010); University of New South Wales, Faculty of Medicine, Sydney, Australia (GRID:grid.1005.4) (ISNI:0000 0004 4902 0432) 
6  The George Institute for Global Health, New Delhi, India (GRID:grid.464831.c) (ISNI:0000 0004 8496 8261); University of New South Wales, Faculty of Medicine, Sydney, Australia (GRID:grid.1005.4) (ISNI:0000 0004 4902 0432) 
7  The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Department of Infectious Diseases, Melbourne, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X) 
8  Australian and New Zealand Intensive Care Research Centre (ANZIC-RC), Monash University, Melbourne, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857); Monash University, Transfusion Research Unit, Melbourne, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857) 
9  Department of Infectious Diseases Westmead Hospital, Westmead, Australia (GRID:grid.413252.3) (ISNI:0000 0001 0180 6477); Institute for Clinical Pathology and Medical Research, NSW Health Pathology, Westmead, Australia (GRID:grid.416088.3) (ISNI:0000 0001 0753 1056); University of Sydney, Sydney Institute for Infectious Diseases, Sydney, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X) 
10  University of Queensland Centre for Clinical Research, Faculty of Medicine & Centre for Translational Anti-infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537); Department of Infectious Diseases, Royal Brisbane and Women’s Hospital, Brisbane, Australia (GRID:grid.416100.2) (ISNI:0000 0001 0688 4634) 
11  University of Melbourne, Department of Respiratory Medicine, The Royal Melbourne Hospital and Department of Medicine, Melbourne, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X) 
12  University of Queensland Centre for Clinical Research, Faculty of Medicine & Centre for Translational Anti-infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537); Department of Infectious Diseases, Royal Brisbane and Women’s Hospital, Brisbane, Australia (GRID:grid.416100.2) (ISNI:0000 0001 0688 4634); Royal Brisbane and Women’s Hospital, Departments of Pharmacy and Intensive Care Medicine, Brisbane, Australia (GRID:grid.416100.2) (ISNI:0000 0001 0688 4634); Nîmes University Hospital, University of Montpellier, Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes, France (GRID:grid.411165.6) (ISNI:0000 0004 0593 8241) 
13  School of Public Health, University of Sydney, Camperdown, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X) 
14  John Hunter Hospital, Department of Infectious Diseases, Newcastle, Australia (GRID:grid.414724.0) (ISNI:0000 0004 0577 6676); Perth Children’s Hospital, Department of Infectious Diseases, Perth, Australia (GRID:grid.410667.2) (ISNI:0000 0004 0625 8600); School of Public Health, University of Sydney, Camperdown, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X) 
15  Perth, Australia (GRID:grid.1013.3) 
16  Middlemore Hospital, Counties Manukau District Health Board, Auckland, New Zealand (GRID:grid.415534.2) (ISNI:0000 0004 0372 0644) 
Pages
1014
Publication year
2022
Publication date
Dec 2022
Publisher
Springer Nature B.V.
e-ISSN
17456215
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1186/s13063-022-06929-y
ProQuest document ID
2753891169
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.