Apixaban to Prevent dEcompensation of eArly Liver CirrHosis Trial
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 1,142
- 主要终点
- Time from randomisation to first decompensation event, assessed up to 49 months
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
- •INR >1.7 (After vitamin K correction) at screening
- •Previous hypersensitivity reaction to Apixaban
结局指标
主要结局
Time from randomisation to first decompensation event, assessed up to 49 months
时间窗: 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
次要结局
- 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)
- Health-related quality of life assessed using EQ-5D-5L questionnaire(Time from randomisation assessed up to 49 months)
- Alcohol use(Time from baseline assessed up to 49 months)
- Time from randomisation to first decompensation event, 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(Time from randomisation assessed up to 49 months)
- Assessment of safety of anticoagulation in Childs A cirrhosis patients(Time from randomisation assessed up to 49 months)
- Time to all-cause mortality(Time from randomisation assessed up to 49 months)