Apixaban for Intrahepatic Non Cirrhotic Portal Hypertension (APIS)

This is an interventional prevention trial for Intrahepatic Non Cirrhotic Portal Hypertension Read More

Inclusion Criteria:

• 18 and ≤ 90 year old male and female patients,
• For child-bearing aged women, contraception using progestatives, or intrauterine device or mechanical contraception
• Adequate prophylaxis against variceal bleeding according to EASL (European association for the study of the liver) guidelines

• Intrahepatic non cirrhotic portal hypertension (INCPH), defined according to the recent VALDIG workshop (Feb. 2017, Ascona, Italy) as having one of the following simultaneous associations:

  1. absence of cirrhosis on an adequate liver biopsy, and one or more signs specific for portal hypertension
  2. absence of cirrhosis on an adequate liver biopsy, and one or more signs not specific for portal hypertension and one or more histological signs for INCPH
  3. in the absence of adequate liver biopsy, 2 reliable liver stiffness values determined using transient elastography (Fibroscan) < 10 kPa and one or more signs specific for portal hypertension

Exclusion Criteria:

• Myeloproliferative disease treated with aspirin to prevent vascular events, paroxysmal nocturnal hemoglobinuria.
• Ongoing oestroprogestative contraception
• Pregnant or breastfeeding women
• Complete thrombosis of superior mesenteric vein and/or inferior mesenteric vein
• Complete portal vein thrombosis or portal cavernoma
• Recent (<6 months) partial portal venous system thrombosis
• Mandatory indication or contraindication for anticoagulation according to guidelines of the American college of chest physicians
• Concomitant treatment with any other anticoagulant agent unless when bridging from one to the other is performed
• Disease at high risk of bleeding (except for portal hypertension)
• Active clinically significant bleeding:. This may include current or recent gastrointestinal ulceration, presence of malignant neoplasms at high risk of bleeding, recent brain or spinal injury, recent brain, spinal or ophthalmic surgery, recent intracranial haemorrhage, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities.
• Platelet < 40000/mm3, or prothrombin index <40% in the absence of anti-vitamin K or Factor V < 40% or Fibrinogen < 1.0g/L
• Transjugular intrahepatic portosystemic shunt (TIPSS) or surgical portosystemic shunt
• Participation in another interventional trial
• Creatinine clearance < 30 mL/min
• Hepatitis C with detectable HCV RNA at inclusion
• Positive HBs Ag, except patients with HBeAg-negative chronic HBV infection, previously termed 'inactive carriers' [characterised by the presence of serum antibodies to HBeAg (anti-HBe), undetectable or low (<2,000 IU/mL) HBV DNA levels and normal serum ALT levels] that can be included
• Alcohol intake >210 g/week for men and 140 g/week for women
• Mandatory indication to aspirin or other antiplatelet agents including P2Y12 receptor antagonists according to guidelines of the American Heart Association
• Patient who underwent liver transplantation less than 3 years before screening
• Severe hepatic impairment or significant active liver injury (serum ALT level > 5 times the upper limit of normal values)
• Life expectancy <12 months
• Specific causes of portal hypertension or specific vascular liver diseases: history of bone marrow transplantation, Budd-Chiari syndrome / hepatic venous outflow obstruction, hepatic schistosomiasis diagnosed on liver biopsy (an isolated positive serology is not an exclusion criterion), cardiac failure, Fontan surgery, Abernethy syndrome, Hereditary hemorrhagic telangiectasia, chronic cholestatic diseases, liver infiltration by tumor cells
• Concomitant use of potent inhibitors of CYP3A4 or P-gp. In case of moderate interactions with apixaban (for example, immunosuppressive treatment), the dose of CYP3A4 inhibitor will be adapted according to its plasmatic level in the study patient.
• Hypersensitivity to the active substance or to any of the excipients including lactose.
• Patients unable to give consent (under guardianship or curatorship)
• No written informed consent for participation in the study
• No coverage for medical insurance