Liver cirrhosis secondary to alcohol, with or without associated metabolic risk factors, i.e. Alcohol Related Liver Disease (ARLD) or metabolic dysfunction-associated steatotic liver disease, where there has been a significant history of alcohol consumption (MetALD) Digestive System
Conditions
Interventions
1. Apixaban 2.5mg film-coated tablets (licenced in the UK and/or approved country)
2. Placebo to match film-coated tablets (same visual appearance, no active ingredients).
Participants will be instruc
Sponsors
University College London
Eligibility
Sex/Gender
All
Age
18 Years to 110 Years
Inclusion criteria
Inclusion criteria: 1. Liver cirrhosis secondary to alcohol, with or without associated metabolic risk factors, i.e. Alcohol related liver disease (ARLD) or metabolic dysfunction-associated steatotic liver disease, where there has been a significant history of alcohol consumption (MetALD) 2. Cirrhosis will be based on histology, or clear radiological evidence, e.g. nodular or heterogeneous liver or non-invasive testing (e.g. Fibroscan®, or Enhanced Liver Fibrosis (ELF) test 3. Childs A Cirrhosis (Participants with a previous episode of decompensated cirrhosis who have now recompensated can be included) 4. Participants with no hepatic encephalopathy or low-grade hepatic encephalopathy (Grade 0 or 1) taking lactulose and/or rifaximin 5. Aged =18 years 6. Clinical evidence of portal hypertension, defined as any 1 of: 6.1. Evidence of abdominal collateral circulation, recanalised umbilical vein or varices on imaging 6.2. Asymptomatic ascites (trace only) seen around the liver on imaging in patients who are not taking diuretics 6.3. Liver stiffness measurement >20kPa on FibroScan®/ Vibration-Controlled Transient Elastography (VCTE) (where BMI 13 cm in length 6.7. Liver stiffness measurement >20kPa on FibroScan®/VCTE (where BMI >35) 6.8. Presence of portal hypertensive gastropathy at endoscopy
Exclusion criteria
Exclusion criteria: 1. Evidence of decompensation (e.g. ascites requiring treatment other than a thin rim around the liver on imaging). (Evidence of decompensation as follows: Grade 2 or 3 Ascites, Grade 2 – 4 Hepatic Encephalopathy, Variceal Haemorrhage). 2. Causes for cirrhosis other than alcohol, including those with MASLD who have never drunk alcohol above government recommended levels (14 units/week) 3. Pre-existing splanchnic vein thrombosis (portal, splenic, mesenteric, and hepatic veins) 4. Use of (and need for) anticoagulation or dual antiplatelet therapy or clopidogrel 5. Platelets 1.7 (after vitamin K correction) at screening 13. Previous hypersensitivity reaction to apixaban
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time from randomisation to first decompensation event, defined as at least one of the following: Grade 2 or 3 ascites according to the International Club of Ascites (ICA), or spontaneous bacterial peritonitis; Grade 2-4 hepatic encephalopathy; variceal haemorrhage (gastrointestinal bleeding secondary to rupture of varices); and liver-related death measured using data collected from Case Report Forms (CRFs) at 6-monthly trial follow-up visits and throughout the trial, when location study teams become aware of these events, as decompensation normally involves hospitalisation | — |
Secondary
| Measure | Time frame |
|---|---|
| Time to event for individual decompensation events, comprising: time to first grade 2 or 3 ascites or spontaneous bacterial peritonitis; time to grade 2-4 hepatic encephalopathy; time to variceal haemorrhage; and time to liver-related death measured using data collected from CRFs at 6-monthly trial follow-up visits;Time to development of grade 1 (small volume) ascites measured using data collected from CRFs at 6-monthly trial follow-up visits;Assessment of the safety of anticoagulation in Child's A cirrhosis patients, including the incidence of clinically relevant combined major bleeding and non-major bleeding during the trial treatment period measured using data collected from CRFs at 6-monthly trial follow-up visits;Time to all-cause mortality measured using data collected from CRFs at 6-monthly trial follow-up visits;Time to portal vein thrombosis or /other thromboembolic events measured using data collected from CRFs at 6-monthly trial follow-up visits;Proportion of participants experiencing cardiac events during the trial measured using data collected from CRFs at 6-monthly trial follow-up visits;Alcohol abstinence measured using the AUDIT-C questionnaire at 6-monthly trial follow-up visits;Health-related quality of life measured using EQ-5D-5L questionnaire at the follow-up visits occurring 12, 24, 36, & 48 months after randomisation | — |
Countries
England, United Kingdom
Contacts
Public ContactLee Webber
Outcome results
None listed