Apixaban to Prevent Decompensation of Early Liver Cirrhosis Trial (APEACH)

Apixaban to Prevent dEcompensation of eArly Liver CirrHosis 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.

Study Overview

• Status: Not yet recruiting
• Conditions: Liver Cirrhosis
• Intervention / Treatment: Drug: Placebo; Drug: Apixaban 2.5 mg twice daily

• Study Type: Interventional
• Enrollment (Estimated): 1142
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: APEACH Trial Team; Phone Number: 0207 670 4813; Email: cctu.apeach@ucl.ac.uk
• Study Contact Backup: Name: Lee Webber; Email: l.webber@ucl.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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:

   • Evidence of abdominal collateral circulation, recanalised umbilical vein or varices on imaging
   • Asymptomatic ascites (trace only) seen around the liver on imaging in patients who are not taking diuretics
   • Liver stiffness measurement >20kPa on FibroScan®/ Vibration- Controlled Transient Elastography (VCTE) (where BMI <35)
   • Presence of Gastro-oesophageal varices at endoscopy
   • Hepatic venous pressure gradient ≥ 10mmHg

Or Platelet count < 150,000 μL AND any 1 of:

• Spleen size >13 cm in length
• Liver stiffness measurement >20kPa on FibroScan®/VCTE (where BMI >35)
• Presence of portal hypertensive gastropathy at endoscopy

Exclusion Criteria:

1. 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)
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 <50x109/L at screening
6. Moderate-severe renal impairment defined as eGFR <30ml/min at screening
7. Recent variceal bleed or untreated large varices
8. Malignancy in last 2 years if unlikely to survive trial because of comorbidity in the location PI's opinion
9. Hepatocellular carcinoma
10. Severe cardiac failure1 or Chronic Obstructive Pulmonary Disease (COPD)
11. Pregnancy
12. INR >1.7 (After vitamin K correction) at screening
13. Previous hypersensitivity reaction to Apixaban

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Participants randomised to receive Apixaban 2.5mg oral tablet twice daily; Participants randomised to receive a matching placebo	Drug: Placebo; Placebo will be given as oral tablet and taken twice daily
Experimental: Participants randomised to receive Apixaban 2.5mg twice daily	Drug: Apixaban 2.5 mg twice daily; Participants randomised to this arm will receive Apixaban 2.5mg twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 from randomisation to first decompensation event, assessed up to 49 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 from randomisation to first decompensation event, assessed up to 49 months
Time to development of grade 1 (small volume) ascites	Small volume ascites	Time from randomisation assessed up to 49 months
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 from randomisation assessed up to 49 months
Time to all-cause mortality		Time from randomisation assessed up to 49 months
Time to portal vein thrombosis or other thromboembolic events		Time from randomisation assessed up to 49 months
Incidence of cardiac events		Time from randomisation assessed up to 49 months
Alcohol use	Alcohol use will be determined by patient reporting on AUDIT-C questionnaire	Time from baseline assessed up to 49 months
Health-related quality of life assessed using EQ-5D-5L questionnaire		Time from randomisation assessed up to 49 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 from baseline assessed up to 49 months
Progression or requirement for TIPSS or transplant as an exploratory outcome		Time from randomisation assessed up to 49 months
Time to diagnosis of hepatocellular carcinoma		Time from randomisation assessed up to 49 months
Disease progression, comparing changes in MELD and scores between beginning and end of trial		Time from randomisation assessed up to 49 months

Collaborators and Investigators

• Sponsor: University College, London
• Collaborators: King's College London; King's College Hospital NHS Trust; University of Nottingham; Imperial College London; The Leeds Teaching Hospitals NHS Trust; Royal Free Hospital NHS Foundation Trust; Liverpool University Hospitals NHS Foundation Trust; University Hospital Southampton NHS Foundation Trust; Hull University Teaching Hospitals NHS Trust; NHS Greater Glasgow and Clyde; University Hospital of Wales; BRITISH LIVER TRUST; The Royal London Hospital, UK
• Investigators: Principal Investigator: Alastair O'Brien, Queen Mary University of London

Study record dates

Study Major Dates

• Study Start (Estimated): July 15, 2026
• Primary Completion (Estimated): October 31, 2030
• Study Completion (Estimated): March 30, 2031

Study Registration Dates

• First Submitted: July 7, 2026
• First Submitted That Met QC Criteria: July 21, 2026
• First Posted (Actual): July 24, 2026

Study Record Updates

• Last Update Posted (Actual): July 24, 2026
• Last Update Submitted That Met QC Criteria: July 21, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Liver Cirrhosis; Apixaban; Metabolic dysfunction-associated steatotic liver disease; MetALD; Alcohol Related Liver Disease (ARLD)
• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Liver Diseases; Fibrosis; Pathological Conditions, Signs and Symptoms; Liver Cirrhosis; apixaban
• Other Study ID Numbers: CCTU 2023-474; 1013519 (Registry Identifier: IRAS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No