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Trial summary and protocol for a phase II randomised placebo-controlled double-blinded trial of Interleukin 1 blockade in Acute Severe Colitis: the IASO trial

INTRODUCTION: Acute severe ulcerative colitis (ASUC) is a severe manifestation of ulcerative colitis (UC) that warrants hospitalisation. Despite significant advances in therapeutic options for UC and in the medical management of steroid-refractory ASUC, the initial treatment paradigm has not changed...

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Autores principales: Thomas, Martin Geoffrey, Bayliss, Carrie, Bond, Simon, Dowling, Francis, Galea, James, Jairath, Vipul, Lamb, Christopher, Probert, Christopher, Timperley-Preece, Elizabeth, Watson, Alastair, Whitehead, Lynne, Williams, John G, Parkes, Miles, Kaser, Arthur, Raine, Tim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398753/
https://www.ncbi.nlm.nih.gov/pubmed/30772849
http://dx.doi.org/10.1136/bmjopen-2018-023765
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author Thomas, Martin Geoffrey
Bayliss, Carrie
Bond, Simon
Dowling, Francis
Galea, James
Jairath, Vipul
Lamb, Christopher
Probert, Christopher
Timperley-Preece, Elizabeth
Watson, Alastair
Whitehead, Lynne
Williams, John G
Parkes, Miles
Kaser, Arthur
Raine, Tim
author_facet Thomas, Martin Geoffrey
Bayliss, Carrie
Bond, Simon
Dowling, Francis
Galea, James
Jairath, Vipul
Lamb, Christopher
Probert, Christopher
Timperley-Preece, Elizabeth
Watson, Alastair
Whitehead, Lynne
Williams, John G
Parkes, Miles
Kaser, Arthur
Raine, Tim
author_sort Thomas, Martin Geoffrey
collection PubMed
description INTRODUCTION: Acute severe ulcerative colitis (ASUC) is a severe manifestation of ulcerative colitis (UC) that warrants hospitalisation. Despite significant advances in therapeutic options for UC and in the medical management of steroid-refractory ASUC, the initial treatment paradigm has not changed since 1955 and is based on the use of intravenous corticosteroids. This treatment is successful in approximately 50% of patients but failure of this and subsequent medical therapy still occurs, with colectomy rates of up to 40% reported. The Interleukin 1 (IL-1) blockade in Acute Severe Colitis (IASO) trial aims to investigate whether antagonism of IL-1 signalling using anakinra in addition to intravenous corticosteroid treatment can improve outcomes in patients with ASUC. METHODS AND ANALYSIS: IASO is a phase II, multicentre, two-arm (parallel group), randomised (1:1), placebo-controlled, double-blinded trial of short-duration anakinra in ASUC. Its primary outcome will be the incidence of medical (eg, infliximab/ciclosporin) or surgical rescue therapy (colectomy) within 10 days following the commencement of intravenous corticosteroid therapy. Secondary outcomes will include disease activity, time to clinical response, time to rescue therapy, colectomy incidence by day 98 post intravenous corticosteroids and safety. The trial aims to recruit 214 patients across 20 sites in the UK. ETHICS AND DISSEMINATION: The trial has received approval from the Cambridge Central Research Ethics Committee (Ref: 17/EE/0347), the Health Research Authority (Ref: 201505) and Clinical Trials Authorisation from the Medicines and Healthcare products Regulatory Agency. We plan to present trial findings at scientific conferences and publish in high-impact peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN43717130; EudraCT 2017-001389-10.
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spelling pubmed-63987532019-03-20 Trial summary and protocol for a phase II randomised placebo-controlled double-blinded trial of Interleukin 1 blockade in Acute Severe Colitis: the IASO trial Thomas, Martin Geoffrey Bayliss, Carrie Bond, Simon Dowling, Francis Galea, James Jairath, Vipul Lamb, Christopher Probert, Christopher Timperley-Preece, Elizabeth Watson, Alastair Whitehead, Lynne Williams, John G Parkes, Miles Kaser, Arthur Raine, Tim BMJ Open Gastroenterology and Hepatology INTRODUCTION: Acute severe ulcerative colitis (ASUC) is a severe manifestation of ulcerative colitis (UC) that warrants hospitalisation. Despite significant advances in therapeutic options for UC and in the medical management of steroid-refractory ASUC, the initial treatment paradigm has not changed since 1955 and is based on the use of intravenous corticosteroids. This treatment is successful in approximately 50% of patients but failure of this and subsequent medical therapy still occurs, with colectomy rates of up to 40% reported. The Interleukin 1 (IL-1) blockade in Acute Severe Colitis (IASO) trial aims to investigate whether antagonism of IL-1 signalling using anakinra in addition to intravenous corticosteroid treatment can improve outcomes in patients with ASUC. METHODS AND ANALYSIS: IASO is a phase II, multicentre, two-arm (parallel group), randomised (1:1), placebo-controlled, double-blinded trial of short-duration anakinra in ASUC. Its primary outcome will be the incidence of medical (eg, infliximab/ciclosporin) or surgical rescue therapy (colectomy) within 10 days following the commencement of intravenous corticosteroid therapy. Secondary outcomes will include disease activity, time to clinical response, time to rescue therapy, colectomy incidence by day 98 post intravenous corticosteroids and safety. The trial aims to recruit 214 patients across 20 sites in the UK. ETHICS AND DISSEMINATION: The trial has received approval from the Cambridge Central Research Ethics Committee (Ref: 17/EE/0347), the Health Research Authority (Ref: 201505) and Clinical Trials Authorisation from the Medicines and Healthcare products Regulatory Agency. We plan to present trial findings at scientific conferences and publish in high-impact peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN43717130; EudraCT 2017-001389-10. BMJ Publishing Group 2019-02-15 /pmc/articles/PMC6398753/ /pubmed/30772849 http://dx.doi.org/10.1136/bmjopen-2018-023765 Text en © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.
spellingShingle Gastroenterology and Hepatology
Thomas, Martin Geoffrey
Bayliss, Carrie
Bond, Simon
Dowling, Francis
Galea, James
Jairath, Vipul
Lamb, Christopher
Probert, Christopher
Timperley-Preece, Elizabeth
Watson, Alastair
Whitehead, Lynne
Williams, John G
Parkes, Miles
Kaser, Arthur
Raine, Tim
Trial summary and protocol for a phase II randomised placebo-controlled double-blinded trial of Interleukin 1 blockade in Acute Severe Colitis: the IASO trial
title Trial summary and protocol for a phase II randomised placebo-controlled double-blinded trial of Interleukin 1 blockade in Acute Severe Colitis: the IASO trial
title_full Trial summary and protocol for a phase II randomised placebo-controlled double-blinded trial of Interleukin 1 blockade in Acute Severe Colitis: the IASO trial
title_fullStr Trial summary and protocol for a phase II randomised placebo-controlled double-blinded trial of Interleukin 1 blockade in Acute Severe Colitis: the IASO trial
title_full_unstemmed Trial summary and protocol for a phase II randomised placebo-controlled double-blinded trial of Interleukin 1 blockade in Acute Severe Colitis: the IASO trial
title_short Trial summary and protocol for a phase II randomised placebo-controlled double-blinded trial of Interleukin 1 blockade in Acute Severe Colitis: the IASO trial
title_sort trial summary and protocol for a phase ii randomised placebo-controlled double-blinded trial of interleukin 1 blockade in acute severe colitis: the iaso trial
topic Gastroenterology and Hepatology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398753/
https://www.ncbi.nlm.nih.gov/pubmed/30772849
http://dx.doi.org/10.1136/bmjopen-2018-023765
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