Apixaban to Prevent Decompensation of Early Liver Cirrhosis Trial
ConditionLiver Cirrhosis
Trial statusNot yet recruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity College, London
About this trial
Liver disease is the only common cause of death that is increasing in numbers. Once people develop severe scarring (cirrhosis), there are no medications proven to help them live longer, healthier lives. Apixaban is already commonly used to prevent or treat blood clots and is known to be safe for those with cirrhosis.
In the early stages of cirrhosis, most people have no symptoms and lead normal lives; this is called "compensated" cirrhosis. However, when the liver stops working properly, they develop "decompensated" cirrhosis, which causes yellow skin, confusion, vomiting of blood and painful fluid build-up. This is serious, and people are extremely unwell with a poor quality of life, often need to go to the hospital and on average only live for 2 more years.
The APEACH trial will investigate whether giving compensated cirrhosis patients Apixaban will help stop them from developing decompensated cirrhosis and stay in good health for longer.
Previous research studies suggest that taking blood-thinning drugs is safe and helpful for cirrhosis. However, these did not have enough participants to be confident enough in the results to recommend use in everyday clinical care.
The APEACH trial will include enough participants to make it clear whether Apixaban is helpful or not.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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)
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
Childs A Cirrhosis (Participants with a previous episode of decompensated cirrhosis who have now recompensated can be included)
Participants with no hepatic encephalopathy or low-grade hepatic encephalopathy (Grade 0 or 1) taking lactulose and/or rifaximin
Disqualifiers
Evidence of decompensation (e.g. ascites requiring treatment other than a thin rim around liver on imaging, as above) (Evidence of decompensation as follows: Grade 2 or 3 Ascites, Grade 2 - 4 Hepatic Encephalopathy, Variceal Haemorrhage)
Causes for cirrhosis other than alcohol, including those with MASLD who have never drunk alcohol above government recommended levels (14 units/week)
Pre-existing splanchnic vein thrombosis (portal, splenic, mesenteric, and hepatic veins)
Use of (and need for) anticoagulation or dual antiplatelet therapy or clopidogrel
Trial design
Design model
Parallel
Treatments tested in this trial
Apixaban 2.5 mg twice daily
DrugParticipants randomised to this arm will receive Apixaban 2.5mg twice daily
Placebo
DrugPlacebo will be given as oral tablet and taken twice daily
Treatment groups
1,142 Participants
are divided into 2 treatment groupsGroup A: Participants randomised to receive Apixaban 2.5mg oral tablet twice dailyPlacebo comparator 1 intervention
Group B: Participants randomised to receive Apixaban 2.5mg twice dailyExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Time from randomisation to first decompensation event, assessed up to 49 months
First decompensation event is 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 METHOD 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
Time frame
Time from randomisation to first decompensation event, assessed up to 49 monthsSecondary outcomes
1
Time from randomisation to first decompensation event, assessed up to 49 months
Time to event for individual decompensation events measured at 6-monthly follow-up visits, assessed up to 49 months
Time frame
Time from randomisation to first decompensation event, assessed up to 49 months2
Time to development of grade 1 (small volume) ascites
Small volume ascites
Time frame
Time from randomisation assessed up to 49 months3
Assessment of safety of anticoagulation in Childs A cirrhosis patients
Assessment of safety of anticoagulation in Childs A cirrhosis patients, including incidence of clinically relevant combined major bleeding and non-major bleeding during trial treatment period
Time frame
Time from randomisation assessed up to 49 months4
Time to all-cause mortality
Time frame
Time from randomisation assessed up to 49 monthsOther outcomes
1
Changes in FibroScan® liver stiffness measurement values, splenic elastography, and ELF values as an exploratory outcome
This will be performed in scan performed and technology available
Time frame
Time from baseline assessed up to 49 months2
Progression or requirement for TIPSS or transplant as an exploratory outcome
Time frame
Time from randomisation assessed up to 49 months3
Time to diagnosis of hepatocellular carcinoma
Time frame
Time from randomisation assessed up to 49 months4
Disease progression, comparing changes in MELD and scores between beginning and end of trial
Time frame
Time from randomisation assessed up to 49 monthsLocations
Sponsors and contacts
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University College, London
Lead sponsor
Royal Free Hospital NHS Foundation Trust
Collaborator
NHS Greater Glasgow and Clyde
Collaborator
University Hospital of Wales
Collaborator
University of Nottingham
Collaborator
Liverpool University Hospitals NHS Foundation Trust
Collaborator
University Hospital Southampton NHS Foundation Trust
Collaborator
King's College Hospital NHS Trust
Collaborator
King's College London
Collaborator
Hull University Teaching Hospitals NHS Trust
Collaborator
Imperial College London
Collaborator
The Leeds Teaching Hospitals NHS Trust
Collaborator
The Royal London Hospital, UK
Collaborator
BRITISH LIVER TRUST
Collaborator
Source ClinicalTrials.gov
This trial is not recruiting at the moment. You can still explore other options: