Clinical trial NCT02555111: Xarelto Versus no Treatment for the Prevention of Recurrent Thrombosis in Patients With Chronic Portal Vein Thrombosis.
Official title: Multicentric Randomized Study of Xarelto Versus no Treatment for the Prevention of Recurrent Thrombosis in Patients With Chronic Portal Vein Thrombosis.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Deep Vein Thrombosis
Chronic Portal Vein Thrombosis
Keywords: thrombosis
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2015-09-21
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Open randomized therapeutic study to assess the efficacy of Xarelto 15mg/day in the recurrence of thromboembolic event compared to an untreated group in patients with chronic portal vein thrombosis without high risk thrombophilia.

Detailed description: Chronic portal vein thrombosis (PVT) is a rare disease, affecting young patients, characterized by permanent obstruction of the portal vein trunk causing portal hypertension. In 60-70% of cases it is related to high risk, moderate or mild prothrombotic risk factors.

Accordingly, there are 2 types of complications from PVT :(i) gastrointestinal haemorrhage related to portal hypertension; and (ii) recurrent thrombosis.

Recurrent thrombosis its most dreaded complication as it may lead to intestinal infarction with a related mortality of 20-60% and a high risk of intestinal insufficiency.

Gastrointestinal haemorrhage related to portal hypertension occurs in 20% patients/year. It is less frequent in patients treated with medical or endoscopic prophylaxis for variceal bleeding.

Retrospective data shows that anticoagulation does not worsen the prognosis, and may conversely improve it. Thus, in patients at risk for gastrointestinal bleeding due to portal hypertension and a mild or moderate risk of recurrent thrombosis, the benefit-risk ratio of anticoagulation therapy is unclear.

The aim of this open randomised trial is to assess the efficacy of Xarelto 15mg/day, a new oral factor Xa inhibitor, in the recurrence of thromboembolic event and the risk of major bleeding compared to an untreated group in patients with chronic portal vein thrombosis without high risk thrombophilia.

The hypothesis of the trial is that treatment with Xarelto® would reduce the risk of recurrence of acute deep vein thrombosis (DVT) regardless location, with limited increase in the risk of hemorrhage in patients with chronic portal thrombosis and no high-risk factors for thrombosis recurrence

This is a national, multicentric, interventional study. 17 french centers already agreed to participate.

296 patients will be included on a 3 years period with 2 to 4 years treatment period. All data will be collected after informed consent will be obtained.

Eligibility criteria: Inclusion Criteria:

* adult patients aged 18 to 90 years old
* Patients either with :

  * Portal cavernoma radiologically confirmed, treated or not by anticoagulant
  * previous history of acute portal thrombosis for more than 6 months confirmed by angio-TDM or angio-MRI, repermeabilized or not
* prophylaxis of gastro-intestinal bleeding due to portal hypertension, as recommended for cirrhosis patients. Upper gastro-intestinal endoscopy for less than 12 months
* clinical examination
* for women of childbearing age, contraception, either mecanichal or intra-uterin device, or oral progestative alone. No oral oestroprogestative contraception is allowed.
* written informed consent
* covered by a social security scheme or French "CMU"

Exclusion Criteria:

* At least one High risk factors of thrombosis recurrence after review by the committee composed of an hepatologist and an hematologist specialist of hemostasis
* Cirrhosis clinically or histologically confirmed or Budd-Chiari syndrome
* Any disease leading to significant coagulopathy and clinically significant bleeding risk (platelets \<50 000, or PT \<30% without VKA, or Factor V \<30% or Fibrinogen \<0,8).
* Personal or familial (1rst degree) history of spontanaeous deep vein thrombosis requiring anticoagulant treatment
* pregnant or breast-feeding women
* History of mesenteric veinous ischemia leading to intestinal resection
* patient infected by HIV and treated by anti-protease
* Formal indication to anticoagulant treatment for any reason
* No possible follow-up
* severe renal injury (creatinin clearance \<30 ml/min)
* Patients receiving a systemic treatment by azoled antifongic agent (such as ketoconazole, itraconazole, voriconazole or posaconazole), or a protease inhibitor. These are strong CYP3A4 and P-gp inhibitors.
* Patients receiving a systemic treatment by rifampicyn or any other strong CYP3A4 inducting/stimulator (phenytoïne, carbamazepine, phenobarbital or millepertuis/Hypericum perforatum)
* Hypersensitvity to rivaroxaban or excipients
* active bleeding, or any condition at risk for significant major bleeding
* Any other concomitant anticoagulant treatment, such as non-fractionnaed heparin, low-molecular weight heparin (enoxaparin, dalteparine, etc...), heparin derivatives (fondaparinux, etc), oral anticoagulant (warfarine, dabigatran etexilate, apixaban, etc) except in case of switch to Xarelto® or, in case of non-fractionnaed heparin administered to maintain central veinous or arterial catheterism permeability
* Concomitant treatment by clopidogrel / Plavix® for acute coronary syndrome
* hepatic transplantation
* Intra-hepatic shunt

Primary outcomes:
measure: Incidence of thromboembolic event in any territory ( splanchnic or extra splanchnic, lower limbs, cerebral veinous thrombosis, pulmonary embolism) or death
timeFrame: 2 years
Secondary outcomes:
measure: Efficacy of xarelto
timeFrame: 2 years
measure: Safety of xarelto
timeFrame: 2 years
measure: Number of hospitalization during follow up.
timeFrame: 2 years
measure: Evaluation of clotting activator marker with and without Xarelto.
timeFrame: 2 years
measure: Duration of hospitalization during follow up.
timeFrame: 2 years
Other outcomes:
Locations:
city: Clichy
country: France
facility: Hôpital Beaujon
Study officials:
affiliation: Hôpital Beaujon - APHP
name: Aurélie Dr Plessier
role: PRINCIPAL_INVESTIGATOR
References: