Active, not recruitingNCT04007289APISUpdated May 25, 2025

Apixaban for Intrahepatic Non Cirrhotic Portal Hypertension

A Phase 3 interventional study of Apixaban and Placebo in Intrahepatic Non Cirrhotic Portal Hypertension, sponsored by Assistance Publique - Hôpitaux de Paris. Active, not recruiting at 1 site in France. Open to participants aged 18 Years to 90 Years. Per ClinicalTrials.gov, last updated 2025-05-25.

Sponsored by Assistance Publique - Hôpitaux de Paris · Phase 3, Interventional, and Prevention

Phase: Phase 3
Study type: Interventional
Enrollment: 166
Allocation: Randomized
Ages: 18 Years to 90 Years
Sex: All

Study 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.

Read the detailed description

The Secondary Objectives are :

To assess the safety of apixaban on: (a) any major bleeding as defined by the ISTH (International Society on Thrombosis and Haemostasis) guidelines; (b) liver toxicity; (c) adverse events and reactions.
To compare the effect of 24 months low dosing of apixaban (2.5 mg x 2/day) versus placebo on the following outcomes, assessed during the 24 months of treatment:
1. - at least one event among: deep vein thrombosis in any location, arterial thrombosis, major bleeding, death
2. - the occurrence of deep vein thrombosis in any location or arterial thrombosis
3. - mortality (global, liver related, non-liver related), and mortality or liver transplantation
4. - each and any event among: liver decompensation, complications of portal hypertension including portal hypertensive related gastrointestinal bleeding, liver transplantation or death;
5. - portal hypertension related features (spleen size, platelet count, size of esophageal varices, portal blood flow velocity) and markers of bacterial translocation and inflammation
6. - liver function
7. - quality of life
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 after randomisation in patients with INCPH according to HIV status
To identify predictors of portal venous system thrombosis and liver related events:
- in the control group: liver and spleen stiffness; portal blood flow velocity; specific coagulation tests; markers of bacterial translocation and inflammation
- in the group receiving apixaban: plasma apixaban levels
To assess treatment compliance
To study the occurrence or extension of portal venous system thrombosis or occurrence of deep vein thrombosis in any location or arterial thrombosis in the 6 months after the 24-month treatment with apixaban versus placebo.

Conditions studied

Intrahepatic Non Cirrhotic Portal Hypertension

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In context

Hypertension, Portal

332 studies on the registry are indexed under Hypertension, Portal; 106 are open to participants now.

This study's enrollment of 166 is above the median of 60 across 206 interventional studies indexed under Hypertension, Portal.

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Lead sponsor

Assistance Publique - Hôpitaux de Paris is the lead sponsor of 3,505 studies on the registry; 1,006 are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 90 Years
Sexes eligible: All
Accepts healthy volunteers: No

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

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

Study design

Phase: Phase 3
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Single (Participant)
Enrollment: 166 participants (actual)

Study arms

Active comparator
APIXABAN
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 comparator
PLACEBO
Placebo, 1 pill per os twice a day (one in the morning and one in the evening) for 24 months.
Drug: Placebo

Interventions

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

What researchers measure

Primary outcomes

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.
Time frame: 24 months

Secondary outcomes

Occurrence of side effects
Any major bleeding as defined by the International Society on Thrombosis and Haemostasis guidelines; liver toxicity; adverse events and reactions.
Time frame: 24 months
Composite endpoint including thrombosis and major bleeding
Cumulative incidence of one event among: deep vein thrombosis in any location, arterial thrombosis, major bleeding, death
Time frame: 24 months
Occurence of vein or arterial thrombosis
Compare the effect of 24 months low dosing of apixaban (2.5 mg x 2/day) versus placebo on one event among: deep vein thrombosis in any location, arterial thrombosis,
Time frame: 24 months
Mortality or liver transplantation
cumulative incidence of death (global, liver related, non liver related) or liver transplantation
Time frame: 24 months
Complications of liver disease
cumulative incidence of liver decompensation, complications of portal hypertension including portal hypertensive related gastrointestinal bleeding, liver transplantation or death;
Time frame: 24 months
Portal hypertension related features
change in size of oesophageal varices
Time frame: 24 months
Portal hypertension related features
platelet count
Time frame: 24 months
Markers of bacterial translocation and inflammation
circulating concentrations of CRP
Time frame: 24 months
Liver function
change in child pugh score
Time frame: 24 months
Liver function
change in MELD score
Time frame: 24 months
Measure of Quality of life
change in quality of life assessed using SF36 questionnaire
Time frame: 24 months
Measure of quality life
change in quality of life assessed using CLDQ questionnaire
Time frame: 24 months
occurrence or the extension of portal venous system thrombosis at 24 months after randomisation in patients with INCPH according to HIV status
Compare 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 after randomisation in patients with INCPH according to HIV status
Time frame: 24 months
predictors of portal venous system thrombosis and liver related events
In group receiving Apixaban : plasma Apixaban levels
Time frame: 24 months
predictors of portal venous system thrombosis and liver related events
in the control group : portal blood flow Velocity
Time frame: 24 months
predictors of portal venous system thrombosis and liver related events
in the control group : stiffness measured using Fibroscan
Time frame: 24 months
predictors of portal venous system thrombosis and liver related events
in the control group : levels of specific coagulation tets (D-dimeres)
Time frame: 24 months
treatment compliance
number of compliant patient
Time frame: 24 months
occurrence or extension of portal venous system thrombosis or occurrence of deep vein thrombosis in any location or arterial thrombosis in the 6 months after the 24-month treatment with apixaban versus placebo
cumulative incidence of extension of portal venous system thrombosis or deep vein thrombosis in any location or arterial thrombosis in the 6 months after the 24-month treatment with apixaban versus placebo
Time frame: 30 months

Study locations

1 site

Beaujon hospital
Clichy, 92110, France

References and documents

Individual participant data

Plan to share: Undecided

No publications or documents are linked to this record.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on May 25, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT04007289
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Responsible party: Sponsor
First posted: Jul 5, 2019
Start date: Jun 24, 2019
Primary completion: Jul 31, 2026 (estimated)
Completion: Dec 31, 2026 (estimated)
Last update: May 25, 2025

Study contacts

Pierre Emmanuel RAUTOU

principal investigator · Assistance Publique - Hôpitaux de Paris

Oversight

Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in May 2025. You cannot join it, but the record below documents what was studied.

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