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

Abstract 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...

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Autores principales:	N. Vergis, V. Patel, K. Bogdanowicz, J. Czyzewska-Khan, F. Fiorentino, E. Day, M. Cross, N. Foster, E. Lord, R. Goldin, E. Forrest, M. Thursz
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Alcoholic hepatitis Interleukin 1β Canakinumab Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/f45e5e1c18fb4154a6fd28e5c0c832cd
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spelling	oai:doaj.org-article:f45e5e1c18fb4154a6fd28e5c0c832cd2021-11-14T12:31:07ZIL-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 hepatitis10.1186/s13063-021-05719-21745-6215https://doaj.org/article/f45e5e1c18fb4154a6fd28e5c0c832cd2021-11-01T00:00:00Zhttps://doi.org/10.1186/s13063-021-05719-2https://doaj.org/toc/1745-6215Abstract 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.N. VergisV. PatelK. BogdanowiczJ. Czyzewska-KhanF. FiorentinoE. DayM. CrossN. FosterE. LordR. GoldinE. ForrestM. ThurszBMCarticleAlcoholic hepatitisInterleukin 1βCanakinumabMedicine (General)R5-920ENTrials, Vol 22, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Alcoholic hepatitis Interleukin 1β Canakinumab Medicine (General) R5-920
spellingShingle	Alcoholic hepatitis Interleukin 1β Canakinumab Medicine (General) R5-920 N. Vergis V. Patel K. Bogdanowicz J. Czyzewska-Khan F. Fiorentino E. Day M. Cross N. Foster E. Lord R. Goldin E. Forrest M. Thursz 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
description	Abstract 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.
format	article
author	N. Vergis V. Patel K. Bogdanowicz J. Czyzewska-Khan F. Fiorentino E. Day M. Cross N. Foster E. Lord R. Goldin E. Forrest M. Thursz
author_facet	N. Vergis V. Patel K. Bogdanowicz J. Czyzewska-Khan F. Fiorentino E. Day M. Cross N. Foster E. Lord R. Goldin E. Forrest M. Thursz
author_sort	N. Vergis
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_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_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_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
publisher	BMC
publishDate	2021
url	https://doaj.org/article/f45e5e1c18fb4154a6fd28e5c0c832cd
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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

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