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

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 i...

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Autores principales: Denholm, Justin T., Venkatesh, Balasubramanian, Davis, Joshua, Bowen, Asha C., Hammond, Naomi E., Jha, Vivekanand, McPhee, Grace, McQuilten, Zoe, O’Sullivan, Matthew V. N., Paterson, David, Price, David, Rees, Megan, Roberts, Jason, Jones, Mark, Totterdell, James, Snelling, Thomas, Trask, Nanette, Morpeth, Susan, Tong, Steven YC
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9747535/
https://www.ncbi.nlm.nih.gov/pubmed/36514143
http://dx.doi.org/10.1186/s13063-022-06929-y
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author Denholm, Justin T.
Venkatesh, Balasubramanian
Davis, Joshua
Bowen, Asha C.
Hammond, Naomi E.
Jha, Vivekanand
McPhee, Grace
McQuilten, Zoe
O’Sullivan, Matthew V. N.
Paterson, David
Price, David
Rees, Megan
Roberts, Jason
Jones, Mark
Totterdell, James
Snelling, Thomas
Trask, Nanette
Morpeth, Susan
Tong, Steven YC
author_facet Denholm, Justin T.
Venkatesh, Balasubramanian
Davis, Joshua
Bowen, Asha C.
Hammond, Naomi E.
Jha, Vivekanand
McPhee, Grace
McQuilten, Zoe
O’Sullivan, Matthew V. N.
Paterson, David
Price, David
Rees, Megan
Roberts, Jason
Jones, Mark
Totterdell, James
Snelling, Thomas
Trask, Nanette
Morpeth, Susan
Tong, Steven YC
author_sort Denholm, Justin T.
collection PubMed
description 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). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-022-06929-y.
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spelling pubmed-97475352022-12-14 ASCOT ADAPT study of COVID-19 therapeutics in hospitalised patients: an international multicentre adaptive platform trial Denholm, Justin T. Venkatesh, Balasubramanian Davis, Joshua Bowen, Asha C. Hammond, Naomi E. Jha, Vivekanand McPhee, Grace McQuilten, Zoe O’Sullivan, Matthew V. N. Paterson, David Price, David Rees, Megan Roberts, Jason Jones, Mark Totterdell, James Snelling, Thomas Trask, Nanette Morpeth, Susan Tong, Steven YC Trials Study Protocol 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). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-022-06929-y. BioMed Central 2022-12-14 /pmc/articles/PMC9747535/ /pubmed/36514143 http://dx.doi.org/10.1186/s13063-022-06929-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Study Protocol
Denholm, Justin T.
Venkatesh, Balasubramanian
Davis, Joshua
Bowen, Asha C.
Hammond, Naomi E.
Jha, Vivekanand
McPhee, Grace
McQuilten, Zoe
O’Sullivan, Matthew V. N.
Paterson, David
Price, David
Rees, Megan
Roberts, Jason
Jones, Mark
Totterdell, James
Snelling, Thomas
Trask, Nanette
Morpeth, Susan
Tong, Steven YC
ASCOT ADAPT study of COVID-19 therapeutics in hospitalised patients: an international multicentre adaptive platform trial
title ASCOT ADAPT study of COVID-19 therapeutics in hospitalised patients: an international multicentre adaptive platform trial
title_full ASCOT ADAPT study of COVID-19 therapeutics in hospitalised patients: an international multicentre adaptive platform trial
title_fullStr ASCOT ADAPT study of COVID-19 therapeutics in hospitalised patients: an international multicentre adaptive platform trial
title_full_unstemmed ASCOT ADAPT study of COVID-19 therapeutics in hospitalised patients: an international multicentre adaptive platform trial
title_short ASCOT ADAPT study of COVID-19 therapeutics in hospitalised patients: an international multicentre adaptive platform trial
title_sort ascot adapt study of covid-19 therapeutics in hospitalised patients: an international multicentre adaptive platform trial
topic Study Protocol
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9747535/
https://www.ncbi.nlm.nih.gov/pubmed/36514143
http://dx.doi.org/10.1186/s13063-022-06929-y
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