Xarelto Versus no Treatment for the Prevention of Recurrent Thrombosis in Patients With Chronic Portal Vein Thrombosis. (RIPORT)

Assistance Publique - Hôpitaux de Paris

Status and phase

Completed

Phase 3

Conditions

Chronic Portal Vein Thrombosis

Deep Vein Thrombosis

Treatments

Drug: Xarelto

Study type

Interventional

Funder types

Other

Identifiers

NCT02555111

AOM 11077 - P 110150

2015-001190-40 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment

112 patients

Sex

All

Ages

18 to 90 years old

Volunteers

No Healthy Volunteers

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