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

Deep Vein Thrombosis Clinical Trial

— RIPORT  

Official title:

Multicentric Randomized Study of Xarelto Versus no Treatment for the Prevention of Recurrent Thrombosis in Patients With Chronic Portal Vein Thrombosis.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02555111
• Other study ID #: AOM 11077 - P 110150
• Secondary ID: 2015-001190-40
• Status: Completed
• Phase: Phase 3
• Start date: September 2015
• Est. completion date: February 2020

Study information

• Verified date: March 2020
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 112
• Est. completion date: February 2020
• Est. primary completion date: February 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Portal Vein Thrombosis
• Deep Vein Thrombosis
• Thrombosis
• Venous Thrombosis

Intervention

Drug:
• Xarelto
15mg/day oral administration during 2 to 4 years (based on the recruitment date).

Locations

Country	Name	City	State
France	Hôpital Beaujon	Clichy

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of thromboembolic event in any territory ( splanchnic or extra splanchnic, lower limbs, cerebral veinous thrombosis, pulmonary embolism) or death	In patients with chronic portal vein thrombosis without high risk thrombophilia, to assess the efficacy of Xarelto in the recurrence of thromboembolic event compared to absence of treatment.	2 years
Secondary	Efficacy of xarelto	Assess the efficacy regarding: - Incidence of Pulmonary embolism, Deep vein thrombosis, Major bleedings and Portal hypertension bleeding, new non bleeding complication of portal hypertension, minor bleeding,	2 years
Secondary	Safety of xarelto	Assess the safety regarding: Toxicity of Xarelto, especially hepatic.; Gastrointestinal clinically relevant non major bleedings related to portal hypertension; Other gastrointestinal clinically relevant non major bleedings; Other adverse events; Survival (12months, 24 months and at the end of the follow up).	2 years
Secondary	Number of hospitalization during follow up.		2 years
Secondary	Evaluation of clotting activator marker with and without Xarelto.		2 years
Secondary	Duration of hospitalization during follow up.		2 years