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.
Přehled studie
Postavení
Podmínky
Intervence / Léčba
Typ studie
Zápis (Odhadovaný)
Fáze
- Fáze 3
Kontakty a umístění
Studijní kontakt
- Jméno: APEACH Trial Team
- Telefonní číslo: 0207 670 4813
- E-mail: cctu.apeach@ucl.ac.uk
Studijní záloha kontaktů
- Jméno: Lee Webber
- E-mail: l.webber@ucl.ac.uk
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dospělý
- Starší dospělý
Přijímá zdravé dobrovolníky
Popis
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
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Prevence
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Čtyřnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Komparátor placeba: Participants randomised to receive Apixaban 2.5mg oral tablet twice daily
Participants randomised to receive a matching placebo
|
Placebo will be given as oral tablet and taken twice daily
|
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Experimentální: Participants randomised to receive Apixaban 2.5mg twice daily
|
Participants randomised to this arm will receive Apixaban 2.5mg twice daily
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Time from randomisation to first decompensation event, assessed up to 49 months
Časové okno: 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
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Time from randomisation to first decompensation event, assessed up to 49 months
Časové okno: 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
Časové okno: Time from randomisation assessed up to 49 months
|
Small volume ascites
|
Time from randomisation assessed up to 49 months
|
|
Assessment of safety of anticoagulation in Childs A cirrhosis patients
Časové okno: Time from randomisation assessed up to 49 months
|
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
Časové okno: Time from randomisation assessed up to 49 months
|
Time from randomisation assessed up to 49 months
|
|
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Time to portal vein thrombosis or other thromboembolic events
Časové okno: Time from randomisation assessed up to 49 months
|
Time from randomisation assessed up to 49 months
|
|
|
Incidence of cardiac events
Časové okno: Time from randomisation assessed up to 49 months
|
Time from randomisation assessed up to 49 months
|
|
|
Alcohol use
Časové okno: Time from baseline assessed up to 49 months
|
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
Časové okno: Time from randomisation assessed up to 49 months
|
Time from randomisation assessed up to 49 months
|
Další výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Changes in FibroScan® liver stiffness measurement values, splenic elastography, and ELF values as an exploratory outcome
Časové okno: Time from baseline assessed up to 49 months
|
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
Časové okno: Time from randomisation assessed up to 49 months
|
Time from randomisation assessed up to 49 months
|
|
|
Time to diagnosis of hepatocellular carcinoma
Časové okno: Time from randomisation assessed up to 49 months
|
Time from randomisation assessed up to 49 months
|
|
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Disease progression, comparing changes in MELD and scores between beginning and end of trial
Časové okno: Time from randomisation assessed up to 49 months
|
Time from randomisation assessed up to 49 months
|
Spolupracovníci a vyšetřovatelé
Sponzor
Spolupracovníci
Vyšetřovatelé
- Vrchní vyšetřovatel: Alastair O'Brien, Queen Mary University of London
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Odhadovaný)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- CCTU 2023-474
- 1013519 (Identifikátor registru: IRAS)
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