IL-1 Signal Inhibition in Alcoholic Hepatitis (Isaiah)
Research type
Research Study
Full title
IL-1 Signal Inhibition in Alcoholic Hepatitis (Isaiah)
IRAS ID
231612
Contact name
Mark Thursz
Contact email
Sponsor organisation
Imperial College London
Eudract number
2017-003724-79
Duration of Study in the UK
2 years, 1 months, 30 days
Research summary
Research Summary
Alcohol consumption causes a spectrum of liver abnormalities and leads to over 2 million deaths per year. Alcoholic hepatitis (AH) is a form of alcoholic liver disease characterised by liver failure in the context of recent and heavy alcohol consumption. The condition carries a high fatality risk: patients with severe AH have a 30% mortality rate 90 days after presenting with the condition and moderate AH carries a mortality rate of 6-10% at 90 days. Currently there are no effective treatments for AH although clinical guidelines recommend the use of a drug called prednisolone. Prednisolone improves survival in patients with severe AH up to 28 days but has no survival advantage at 90 days.
Levels of a certain type of protein (IL-1) that plays a role in regulating the immune response to infections are known to be high in patients with AH and it is thought IL-1 is responsible for many of the clinical symptoms of AH. This trial therefore plans to look at the use of a drug which inhibits IL-1 in a multicentre, double blind, randomised placebo controlled trial in 52 patients at 10 sites in the UK in which half of the patients receive canakinumab and half received a placebo. The trial will look at whether or not the drug reduces inflammation in the liver at 28 days by looking at improvement of inflammation on liver biopsy samples and therefore whether it could potentially be a more effective treatment for AH patients.
Summary of Results
Short-term death rate in patients with alcohol-related hepatitis (AH) is high, and no current therapy results in a lasting benefit. This study explored the safety and efficacy of a drug called canakinumab in the treatment of patients with AH. Participants were identified from NHS hospitals across the UK. Fifty-seven participants with AH were randomised (ie had a equal chance of being assigned) to either receive canakinumab or a placebo (‘dummy’ drug’). Very small samples of liver tissue were taken (liver biopsies) before and 28 days after treatment with the drug or placebo. The main objective of the study was to look at improvement in the liver tissue (a reduction in inflammation) between these two timepoints to determine whether or not more improvement was seen in those participants taking canakinumab.
The study found that the drug canakinumab did not affect the clinical outcomes of the participants compared with participants who had placebo. There was some improvement seen in the liver tissue of participants taking canakinumab but this was not a significant improvement and did not result in any overall clinical improvement seen in the participants.REC name
London - Harrow Research Ethics Committee
REC reference
18/LO/0745
Date of REC Opinion
10 Jul 2018
REC opinion
Further Information Favourable Opinion