Apixaban to Prevent Decompensation of Early Liver Cirrhosis Trial

Official title

Apixaban to Prevent dEcompensation of eArly Liver CirrHosis Trial

Overview

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.

Interventions

• Drug Apixaban 2.5 mg twice daily
  Participants randomised to this arm will receive Apixaban 2.5mg twice daily
• Drug Placebo
  Placebo will be given as oral tablet and taken twice daily

Primary outcome measures

• Time from randomisation to first decompensation event, assessed up to 49 months [Time frame: Time from randomisation to first decompensation event, assessed up to 49 months]

Secondary outcome measures (8)

• Time from randomisation to first decompensation event, assessed up to 49 months [Time frame: Time from randomisation to first decompensation event, assessed up to 49 months]
• Time to development of grade 1 (small volume) ascites [Time frame: Time from randomisation assessed up to 49 months]
• Assessment of safety of anticoagulation in Childs A cirrhosis patients [Time frame: Time from randomisation assessed up to 49 months]
• Time to all-cause mortality [Time frame: Time from randomisation assessed up to 49 months]
• Time to portal vein thrombosis or other thromboembolic events [Time frame: Time from randomisation assessed up to 49 months]
• Incidence of cardiac events [Time frame: Time from randomisation assessed up to 49 months]
• Alcohol use [Time frame: Time from baseline assessed up to 49 months]
• Health-related quality of life assessed using EQ-5D-5L questionnaire [Time frame: Time from randomisation assessed up to 49 months]

Eligibility criteria

Inclusion criteria

• 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
• Aged ≥18 years
• 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

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Prevention

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07726693 · CCTU 2023-474 · 1013519

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗