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IL-1 Signal Inhibition In Alcoholic Hepatitis (ISAIAH): a study protocol for a multicentre, randomised, placebo-controlled trial to explore the potential benefits of canakinumab in the treatment of alcoholic hepatitis

BACKGROUND: Alcohol consumption causes a spectrum of liver abnormalities and leads to over 3 million deaths per year. Alcoholic hepatitis (AH) is a florid presentation of alcoholic liver disease characterized by liver failure in the context of recent and heavy alcohol consumption. The aim of this st...

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Autores principales: Vergis, N., Patel, V., Bogdanowicz, K., Czyzewska-Khan, J., Fiorentino, F., Day, E., Cross, M., Foster, N., Lord, E., Goldin, R., Forrest, E., Thursz, M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581959/
https://www.ncbi.nlm.nih.gov/pubmed/34763711
http://dx.doi.org/10.1186/s13063-021-05719-2
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author Vergis, N.
Patel, V.
Bogdanowicz, K.
Czyzewska-Khan, J.
Fiorentino, F.
Day, E.
Cross, M.
Foster, N.
Lord, E.
Goldin, R.
Forrest, E.
Thursz, M.
author_facet Vergis, N.
Patel, V.
Bogdanowicz, K.
Czyzewska-Khan, J.
Fiorentino, F.
Day, E.
Cross, M.
Foster, N.
Lord, E.
Goldin, R.
Forrest, E.
Thursz, M.
author_sort Vergis, N.
collection PubMed
description BACKGROUND: Alcohol consumption causes a spectrum of liver abnormalities and leads to over 3 million deaths per year. Alcoholic hepatitis (AH) is a florid presentation of alcoholic liver disease characterized by liver failure in the context of recent and heavy alcohol consumption. The aim of this study is to explore the potential benefits of the IL-1β antibody, canakinumab, in the treatment of AH. METHODS: This is a multicentre, double-blind, randomised placebo-controlled trial. Participants will be diagnosed with AH using clinical criteria. Liver biopsy will then confirm that all histological features of AH are present. Up to 58 participants will be recruited into two groups from 15 centres in the UK. Patients will receive an infusion of Canakinumab or matched placebo by random 1:1 allocation. The primary outcome is the difference between groups in the proportion of patients demonstrating histological improvement and will compare histological appearances at baseline with appearances at 28 days to assign a category of “improved” or “not improved”. Patients with evidence of ongoing disease activity will receive a second infusion of canakinumab or placebo. Participants will be followed up for 90 days. Secondary outcomes include mortality and change in MELD score at 90 days. DISCUSSION: This phase II study will explore the benefits of the IL-1β antibody, canakinumab, in the treatment of AH to provide proof of concept that inhibition of IL-1β signalling may improve histology and survival for patients with AH. TRIAL REGISTRATION: EudraCT 2017-003724-79. Prospectively registered on 13 April 2018.
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spelling pubmed-85819592021-11-12 IL-1 Signal Inhibition In Alcoholic Hepatitis (ISAIAH): a study protocol for a multicentre, randomised, placebo-controlled trial to explore the potential benefits of canakinumab in the treatment of alcoholic hepatitis Vergis, N. Patel, V. Bogdanowicz, K. Czyzewska-Khan, J. Fiorentino, F. Day, E. Cross, M. Foster, N. Lord, E. Goldin, R. Forrest, E. Thursz, M. Trials Study Protocol BACKGROUND: Alcohol consumption causes a spectrum of liver abnormalities and leads to over 3 million deaths per year. Alcoholic hepatitis (AH) is a florid presentation of alcoholic liver disease characterized by liver failure in the context of recent and heavy alcohol consumption. The aim of this study is to explore the potential benefits of the IL-1β antibody, canakinumab, in the treatment of AH. METHODS: This is a multicentre, double-blind, randomised placebo-controlled trial. Participants will be diagnosed with AH using clinical criteria. Liver biopsy will then confirm that all histological features of AH are present. Up to 58 participants will be recruited into two groups from 15 centres in the UK. Patients will receive an infusion of Canakinumab or matched placebo by random 1:1 allocation. The primary outcome is the difference between groups in the proportion of patients demonstrating histological improvement and will compare histological appearances at baseline with appearances at 28 days to assign a category of “improved” or “not improved”. Patients with evidence of ongoing disease activity will receive a second infusion of canakinumab or placebo. Participants will be followed up for 90 days. Secondary outcomes include mortality and change in MELD score at 90 days. DISCUSSION: This phase II study will explore the benefits of the IL-1β antibody, canakinumab, in the treatment of AH to provide proof of concept that inhibition of IL-1β signalling may improve histology and survival for patients with AH. TRIAL REGISTRATION: EudraCT 2017-003724-79. Prospectively registered on 13 April 2018. BioMed Central 2021-11-11 /pmc/articles/PMC8581959/ /pubmed/34763711 http://dx.doi.org/10.1186/s13063-021-05719-2 Text en © The Author(s) 2021 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
Vergis, N.
Patel, V.
Bogdanowicz, K.
Czyzewska-Khan, J.
Fiorentino, F.
Day, E.
Cross, M.
Foster, N.
Lord, E.
Goldin, R.
Forrest, E.
Thursz, M.
IL-1 Signal Inhibition In Alcoholic Hepatitis (ISAIAH): a study protocol for a multicentre, randomised, placebo-controlled trial to explore the potential benefits of canakinumab in the treatment of alcoholic hepatitis
title IL-1 Signal Inhibition In Alcoholic Hepatitis (ISAIAH): a study protocol for a multicentre, randomised, placebo-controlled trial to explore the potential benefits of canakinumab in the treatment of alcoholic hepatitis
title_full IL-1 Signal Inhibition In Alcoholic Hepatitis (ISAIAH): a study protocol for a multicentre, randomised, placebo-controlled trial to explore the potential benefits of canakinumab in the treatment of alcoholic hepatitis
title_fullStr IL-1 Signal Inhibition In Alcoholic Hepatitis (ISAIAH): a study protocol for a multicentre, randomised, placebo-controlled trial to explore the potential benefits of canakinumab in the treatment of alcoholic hepatitis
title_full_unstemmed IL-1 Signal Inhibition In Alcoholic Hepatitis (ISAIAH): a study protocol for a multicentre, randomised, placebo-controlled trial to explore the potential benefits of canakinumab in the treatment of alcoholic hepatitis
title_short IL-1 Signal Inhibition In Alcoholic Hepatitis (ISAIAH): a study protocol for a multicentre, randomised, placebo-controlled trial to explore the potential benefits of canakinumab in the treatment of alcoholic hepatitis
title_sort il-1 signal inhibition in alcoholic hepatitis (isaiah): a study protocol for a multicentre, randomised, placebo-controlled trial to explore the potential benefits of canakinumab in the treatment of alcoholic hepatitis
topic Study Protocol
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581959/
https://www.ncbi.nlm.nih.gov/pubmed/34763711
http://dx.doi.org/10.1186/s13063-021-05719-2
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