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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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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
Authors: 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
Item Type: Journal Article
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 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 United Kingdom. Patients will receive an infusion of Canakinumab or matched placebo by random 1:1 allocation. The primary outcome is reduction in lobular inflammation, comparing histological appearances at baseline with appearances at 28 days. 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 signaling may improve histology and survival for patients with AH. Trial registration: Prospectively registered with EudraCT 2017-003724-79.
Issue Date: 11-Nov-2021
Date of Acceptance: 12-Oct-2021
URI: http://hdl.handle.net/10044/1/92658
DOI: 10.1186/s13063-021-05719-2
ISSN: 1745-6215
Publisher: BioMed Central
Start Page: 1
End Page: 16
Journal / Book Title: Trials
Volume: 22
Issue: 792
Copyright Statement: © The Author(s). 2021 Open Access This 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/. The Creative Commons Public Domain Dedication waiver (http://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.
Sponsor/Funder: Novartis
Funder's Grant Number: CACZ885P2201T
Keywords: Science & Technology
Life Sciences & Biomedicine
Medicine, Research & Experimental
Research & Experimental Medicine
Alcoholic hepatitis
Interleukin 1 beta
Canakinumab
SCORING SYSTEM
PREDNISOLONE
PENTOXIFYLLINE
Alcoholic hepatitis
Canakinumab
Interleukin 1β
Antibodies, Monoclonal, Humanized
Clinical Trials, Phase II as Topic
Double-Blind Method
Hepatitis, Alcoholic
Humans
Multicenter Studies as Topic
Randomized Controlled Trials as Topic
Treatment Outcome
1102 Cardiorespiratory Medicine and Haematology
1103 Clinical Sciences
General & Internal Medicine
Cardiovascular System & Hematology
Publication Status: Published
Online Publication Date: 2021-11-11
Appears in Collections:Department of Metabolism, Digestion and Reproduction



This item is licensed under a Creative Commons License Creative Commons