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

on behalf of the ASCOT ADAPT investigators

doi:10.1186/s13063-022-06929-y

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

on behalf of the ASCOT ADAPT investigators

Menzies School of Health Research

Research output: Contribution to journal › Article › peer-review

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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).

Original language	English
Article number	1014
Pages (from-to)	1-11
Number of pages	11
Journal	Trials
Volume	23
Issue number	1
DOIs	https://doi.org/10.1186/s13063-022-06929-y
Publication status	Published - Dec 2022

Bibliographical note

Funding Information:
Biological specimens collected for ASCOT ADAPT are stored in participating biobank facilities, with a central ‘virtual biobank’ catalogue of samples and consent. Samples are collected, processed and stored according to central laboratory procedures. Access to samples for ethics-approved protocols is considered through a central biobank committee, where guiding principles for access are equity and maximising scientific value. Storage of specimens is provided by the ASCOT ADAPT study, with retrieval and transport costs funded by external researchers accessing specimens.

Publisher Copyright:
© 2022, The Author(s).

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/s13063-022-06929-y

65718777-oaFinal published version, 1.44 MBLicence: CC BY

Cite this

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title = "ASCOT ADAPT study of COVID-19 therapeutics in hospitalised patients: An international multicentre adaptive platform trial",

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",

author = "{on behalf of the ASCOT ADAPT investigators} and Denholm, {Justin T.} and Balasubramanian Venkatesh and Joshua Davis and Bowen, {Asha C.} and Hammond, {Naomi E.} and Vivekanand Jha and Grace McPhee and Zoe McQuilten and O{\textquoteright}Sullivan, {Matthew V.N.} and David Paterson and David Price and Megan Rees and Jason Roberts and Mark Jones and James Totterdell and Thomas Snelling and Nanette Trask and Susan Morpeth and Tong, {Steven Yc}",

note = "Funding Information: Biological specimens collected for ASCOT ADAPT are stored in participating biobank facilities, with a central {\textquoteleft}virtual biobank{\textquoteright} catalogue of samples and consent. Samples are collected, processed and stored according to central laboratory procedures. Access to samples for ethics-approved protocols is considered through a central biobank committee, where guiding principles for access are equity and maximising scientific value. Storage of specimens is provided by the ASCOT ADAPT study, with retrieval and transport costs funded by external researchers accessing specimens. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1186/s13063-022-06929-y",

language = "English",

volume = "23",

pages = "1--11",

journal = "Trials",

issn = "1745-6215",

publisher = "BioMed Central",

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T1 - ASCOT ADAPT study of COVID-19 therapeutics in hospitalised patients

T2 - An international multicentre adaptive platform trial

AU - on behalf of the ASCOT ADAPT investigators

AU - Denholm, Justin T.

AU - Venkatesh, Balasubramanian

AU - Davis, Joshua

AU - Bowen, Asha C.

AU - Hammond, Naomi E.

AU - Jha, Vivekanand

AU - McPhee, Grace

AU - McQuilten, Zoe

AU - O’Sullivan, Matthew V.N.

AU - Paterson, David

AU - Price, David

AU - Rees, Megan

AU - Roberts, Jason

AU - Jones, Mark

AU - Totterdell, James

AU - Snelling, Thomas

AU - Trask, Nanette

AU - Morpeth, Susan

AU - Tong, Steven Yc

N1 - Funding Information: Biological specimens collected for ASCOT ADAPT are stored in participating biobank facilities, with a central ‘virtual biobank’ catalogue of samples and consent. Samples are collected, processed and stored according to central laboratory procedures. Access to samples for ethics-approved protocols is considered through a central biobank committee, where guiding principles for access are equity and maximising scientific value. Storage of specimens is provided by the ASCOT ADAPT study, with retrieval and transport costs funded by external researchers accessing specimens. Publisher Copyright: © 2022, The Author(s).

PY - 2022/12

Y1 - 2022/12

N2 - 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).

AB - 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).

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KW - Anticoagulation

KW - Antiviral medication

KW - COVID-19

KW - Randomised controlled trial

KW - SARS-CoV-2

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ER -

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

Abstract

Bibliographical note

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