Multicenter Study

. 2022 Dec 14;23(1):1014.

doi: 10.1186/s13063-022-06929-y.

ASCOT ADAPT study of COVID-19 therapeutics in hospitalised patients: an international multicentre adaptive platform trial

Justin T Denholm^{1

2}, Balasubramanian Venkatesh^{3

4

5}, Joshua Davis^{6

7}, Asha C Bowen^{6

8

9}, Naomi E Hammond^{3

5}, Vivekanand Jha^{4

5}, Grace McPhee², Zoe McQuilten^{10

11}, Matthew V N O'Sullivan^{12

13

14}, David Paterson^{15

16}, David Price², Megan Rees¹⁷, Jason Roberts^{15

16

18

19}, Mark Jones²⁰, James Totterdell²⁰, Thomas Snelling^{7

8

20}, Nanette Trask²¹, Susan Morpeth²², Steven Yc Tong^{23

24}; ASCOT ADAPT investigators

Affiliations

¹ Victorian Infectious Diseases Service, The Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
² Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia.
³ The George Institute for Global Health, Sydney, Australia.
⁴ The George Institute for Global Health, New Delhi, India.
⁵ Faculty of Medicine, University of New South Wales, Sydney, Australia.
⁶ Menzies School of Health Research, Charles Darwin University, Darwin, Australia.
⁷ Department of Infectious Diseases, John Hunter Hospital, Newcastle, NSW, Australia.
⁸ Department of Infectious Diseases, Perth Children's Hospital, Perth, Australia.
⁹ Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, Perth, Australia.
¹⁰ Australian and New Zealand Intensive Care Research Centre (ANZIC-RC), Monash University, Melbourne, Australia.
¹¹ Transfusion Research Unit, Monash University, Melbourne, Australia.
¹² Department of Infectious Diseases Westmead Hospital, Westmead, Australia.
¹³ NSW Health Pathology, Institute for Clinical Pathology and Medical Research, Westmead, Australia.
¹⁴ Sydney Institute for Infectious Diseases, University of Sydney, Sydney, Australia.
¹⁵ 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.
¹⁶ Department of Infectious Diseases, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
¹⁷ Department of Respiratory Medicine, The Royal Melbourne Hospital and Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
¹⁸ Departments of Pharmacy and Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia.
¹⁹ Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France.
²⁰ School of Public Health, University of Sydney, Camperdown, Australia.
²¹ , Perth, Australia.
²² Middlemore Hospital, Counties Manukau District Health Board, Auckland, New Zealand.
²³ Victorian Infectious Diseases Service, The Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia. Steven.tong@mh.org.au.
²⁴ Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia. Steven.tong@mh.org.au.

PMID: 36514143
PMCID: PMC9747535
DOI: 10.1186/s13063-022-06929-y

Multicenter Study

ASCOT ADAPT study of COVID-19 therapeutics in hospitalised patients: an international multicentre adaptive platform trial

Justin T Denholm et al. Trials. 2022.

. 2022 Dec 14;23(1):1014.

doi: 10.1186/s13063-022-06929-y.

Authors

Affiliations

¹ Victorian Infectious Diseases Service, The Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
² Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia.
³ The George Institute for Global Health, Sydney, Australia.
⁴ The George Institute for Global Health, New Delhi, India.
⁵ Faculty of Medicine, University of New South Wales, Sydney, Australia.
⁶ Menzies School of Health Research, Charles Darwin University, Darwin, Australia.
⁷ Department of Infectious Diseases, John Hunter Hospital, Newcastle, NSW, Australia.
⁸ Department of Infectious Diseases, Perth Children's Hospital, Perth, Australia.
⁹ Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, Perth, Australia.
¹⁰ Australian and New Zealand Intensive Care Research Centre (ANZIC-RC), Monash University, Melbourne, Australia.
¹¹ Transfusion Research Unit, Monash University, Melbourne, Australia.
¹² Department of Infectious Diseases Westmead Hospital, Westmead, Australia.
¹³ NSW Health Pathology, Institute for Clinical Pathology and Medical Research, Westmead, Australia.
¹⁴ Sydney Institute for Infectious Diseases, University of Sydney, Sydney, Australia.
¹⁵ 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.
¹⁶ Department of Infectious Diseases, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
¹⁷ Department of Respiratory Medicine, The Royal Melbourne Hospital and Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
¹⁸ Departments of Pharmacy and Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia.
¹⁹ Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France.
²⁰ School of Public Health, University of Sydney, Camperdown, Australia.
²¹ , Perth, Australia.
²² Middlemore Hospital, Counties Manukau District Health Board, Auckland, New Zealand.
²³ Victorian Infectious Diseases Service, The Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia. Steven.tong@mh.org.au.
²⁴ Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia. Steven.tong@mh.org.au.

PMID: 36514143
PMCID: PMC9747535
DOI: 10.1186/s13063-022-06929-y

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).

Keywords: Antibody; Anticoagulation; Antiviral medication; COVID-19; Randomised controlled trial; SARS-CoV-2.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

**Fig. 1**
Patient flow if eligible for platform entry

**Fig. 3**
Key governance structures overseeing the trial implementation and conduct

See this image and copyright information in PMC

References

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1. Denholm JT, David J, Paterson D, et al. The Australasian COVID-19 Trial (ASCOT) to assess clinical outcomes in hospitalised patients with SARS-CoV-2 infection (COVID-19) treated with lopinavir/ritonavir and/or hydroxychloroquine compared to standard of care: a structured summary of a study protocol for a randomised controlled trial. Trials. 2020;21(1):1–3. doi: 10.1186/s13063-020-04576-9. - DOI - PMC - PubMed
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ASCOT ADAPT study of COVID-19 therapeutics in hospitalised patients: an international multicentre adaptive platform trial

Affiliations

ASCOT ADAPT study of COVID-19 therapeutics in hospitalised patients: an international multicentre adaptive platform trial

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Associated data

LinkOut - more resources

Full Text Sources

Medical

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