Apixaban for Intrahepatic Non Cirrhotic Portal Hypertension

NCT04007289 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: P170916J
• Study Type: interventional
• Target: 166
• Locations: 1 country
• Sites: 1

Brief Summary

Intrahepatic non-cirrhotic portal hypertension (INCPH) is a rare disease mostly affecting adults in their forties, characterized by portal hypertension related to alterations of intrahepatic microcirculation in the absence of cirrhosis.The only therapeutic options currently available for patients with INCPH include prophylaxis for variceal bleeding using betablockers and/or endoscopic band ligation and TIPSS (transjugular intrahepatic portosystemic shunt) or liver transplantation for severe cases. The investigators hypothesize that anticoagulation using Apixaban in patients with INCPH might prevent occurrence or extension of portal, splenic or mesenteric veins thromboses and thus the development of chronic portal vein thrombosis and associated complications, but also avoid intrahepatic thromboses and consequently liver disease progression and variceal bleeding. The Primary Objective is to evaluate the effect of 24 months low dosing of apixaban (2.5 mg x 2/day) versus placebo on the occurrence or the extension of portal venous system thrombosis (including splenic, mesenteric veins, portal trunk or left or right portal branches) at 24 months in patients with INCPH. 166 patients will be included in 21 centers in a prospective, national multicentric, phase III, superiority comparative randomized (1:1) double-blinded clinical trial with two parallel arms: apixaban versus placebo.

Conditions

Intrahepatic Non Cirrhotic Portal Hypertension

Outcome Measures

Primary Outcomes (1)

• Portal venous system thrombosis

  Occurrence or extension of portal venous system thrombosis (including splenic, mesenteric veins, portal trunk or left or right portal branches) at 24 months in patients with INCPH.

  24 months

Secondary Outcomes (19)

• Occurrence of side effects

  24 months

• Composite endpoint including thrombosis and major bleeding

  24 months

• Occurence of vein or arterial thrombosis

  24 months

• Mortality or liver transplantation

  24 months

• Complications of liver disease

  24 months

Study Arms (2)

APIXABAN

ACTIVE COMPARATOR

Apixaban, 1 pill of 2.5 mg per os twice a day (one in the morning and one in the evening) for 24 months.

Drug: Apixaban

PLACEBO

PLACEBO COMPARATOR

Placebo, 1 pill per os twice a day (one in the morning and one in the evening) for 24 months.

Drug: Placebo

Interventions

Apixaban DRUG

Administration of Apixaban ; 2 clinical examinations; blood tests, 3 liver and spleen stiffness measurements, 2 contrast enhanced echocardiographies, 1 hepatic ultrasonography, Biological samples collections to identify predictors of thrombosis and liver related events

APIXABAN

Placebo DRUG

Administration of placebo ; 2 clinical examinations; blood tests, 3 liver and spleen stiffness measurements, 2 contrast enhanced echocardiographies, 1 hepatic ultrasonography,

PLACEBO

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• absence of cirrhosis on an adequate liver biopsy, and one or more signs specific for portal hypertension
• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Beaujon hospital

Clichy, France, 92110, France

Location

MeSH Terms

Interventions

apixaban

Study Officials

• Pierre Emmanuel RAUTOU

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: double blind
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study will be a prospective, national multicentric, phase III, superiority comparative randomized (1:1) double-blinded clinical trial with two parallel arms: apixaban versus placebo.

Study Record Dates

• First Submitted: May 24, 2019
• First Posted: July 5, 2019
• Study Start: June 24, 2019
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 25, 2025

Record last verified: 2025-05

Locations

FR (1)