Clinical trial NCT02643212: Multicenter Prospective Randomized Trial of the Effect of Rivaroxaban on Survival and Development of Complications of Portal Hypertension in Patients With Cirrhosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Cirrhosis
Lead sponsor: Hospital Clinic of Barcelona
Sponsor class: OTHER
Collaborators: name: IDIBAPS - Dr. Juan Carlos García Pagán
First posted: 2015-12-31
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main objective of the study will determine if patients with liver cirrhosis, anticoagulation free survival improves hypertension decompensation portal and / or transplantation without serious side effects. For it is conduct a double-blind multicenter clinical trial in which patients will be randomized to receive Rivaroxaban or placebo. It included 160 patients with liver cirrhosis and insufficiency mild to moderate hepatic. It will also analyze and develop secondary endpoint portal vein thrombosis. The confirmation of our hypothesis would lead to a radical change in treatment of patients with cirrhosis include treatment with Rivaroxaban in its drove.


Eligibility criteria: Inclusion Criteria:

* Aged between 18 and 75 years of both sexes.
* Clinical and / or laboratory criteria, ultrasound and / or liver biopsy compatible with the diagnosis of viral cirrhosis (If hepatitis B virus: hepatitis B virus-DNA must be negative; if hepatitis C virus: sustained virologic response should be at least for 6 months prior to enrollment); alcohol (in the last 6 months: in men less than 60 g daily intake in women less than 40 g); nonalcoholic steatohepatitis and cryptogenic.
* Presence of clinically significant portal hypertension defined by clinical criteria (presence of esophageal varices or ascites), elastography (liver Fibroscan® ? 21 kPa) or hemodynamic (Hepatic venous pressure gradient \> 10 mmHg)
* Mild to moderate hepatic impairment defined by Child-Pugh of 7-10 points.
* Written informed consent to participate in the study

Exclusion Criteria:

* Any previous or current thrombosis in splenoportal axis (must be ruled out by US-Doppler earlier than one month after randomization; if doubts: computed tomography angiography or magnetic resonance angiography if required).
* Background of hepatic encephalopathy grade II or higher
* Ascites that required prior practice of paracentesis in the last year d. Indication for use of anticoagulant and / or antiplatelet therapy for any reason.
* Hypersensitivity to the active ingredient or to excipients
* Active bleeding, clinically significant, or risk of major bleeding.
* Pregnancy and lactation.
* Hepatocellular carcinoma or malignant neoplasia at the time of inclusion.
* Any comorbidity involving a therapeutic limitation and/or a life expectancy \<12 months.
* Existence of risk bleeding esophageal varices or prior variceal bleeding. They may not be included until full treatment (stable beta blockers dosage or eradication trough varices ligation).
* Pregnancy or lactation.
* Severe thrombocytopenia \<40,000 platelets / dl.
* Kidney failure (creatinine clearance \<15ml / min).
* Transjugular intrahepatic portosystemic shunt or portosystemic shunt carrier.
* Child-Pugh score greater than 10.
* In hepatitis C virus liver cirrhosis patients: not carrying at least six months in sustained virologic response. In hepatitis B virus liver cirrhosis patients: hepatitis B virus DNA is not negative .
* Active alcoholism (60 g / day in men and 40 in women)
* Use of potent inhibitors of cytochrome cytochrome P450 3A4 (ketoconazole, protease inhibitor antiretroviral treatment in human immunodeficiency virus patients) or cytochrome inductors (rifampicin. Phenytoin ...).
* Participation in another clinical trial

Primary outcomes:
measure: Survival free of transplant and decompensation / complications of portal hypertension.
timeFrame: At month 24
Secondary outcomes:
measure: Cirrhosis progression disease (bleeding episode, encephalopathy, ascitis)
timeFrame: At month 24
measure: Development of portal vein thrombosis detected by ultrasound and confirmed by CT angiography or MRI angiography
timeFrame: At month 24
measure: To evaluate the efficacy in preventing complications of portal hypertension
timeFrame: At month 24
measure: Security of rivaroxaban in patients with liver cirrhosis, number of adverse events and adverse reactions in each arm of study. History and clinical evaluation of bleeding and monitoring of hematocrit. Evaluation of liver function
timeFrame: At month 24
measure: To evaluate the incidence of hepatocellular carcinoma
timeFrame: At month 24
measure: Effect on splenic and liver elasticity measured by fibroscan and / or acoustic radiation force impulse.
timeFrame: At month 24
measure: Effect of Rivaroxaban on hepatocellular function estimated by the Child-Pugh and the model for end-stage liver disease scores.
timeFrame: At month 24
measure: To correlate levels of anti-factor Xa and Rivaroxaban on survival free of transplant, cirrhosis progression disease (bleeding episode, encephalopathy, ascitis) and number of adverse events and reactions.
timeFrame: At month 24
measure: To evaluate the effect of Rivaroxaban on hepatic venous pressure gradient
timeFrame: At month 24
measure: To assess if Rivaroxaban reduces concentration of intestinal fatty acid binding protein, 16S ribosomal DNA, CD14, interleukin 6, lipopolysaccharide binding protein and lipopolysaccharide
timeFrame: At month 24
Other outcomes:
Locations:
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Asturias
city: Badalona
country: Spain
facility: Hospital German Trias i Pujol
state: Barcelona
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge
state: Barcelona
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
state: Cantabria
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro de Majadahonda
state: Madrid
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau.
city: Barcelona
country: Spain
facility: Hospital Vall d´Hebron
city: Barcelona
country: Spain
facility: Hospital Clínic i Provincial de Barcelona
city: Lérida
country: Spain
facility: Hospital Arnau de Vilanova
city: Madrid
country: Spain
facility: Hospital Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Pontevedra
country: Spain
facility: Complejo Hospitalario de Pontevedra_Hospital Montecelo
city: Tenerife
country: Spain
facility: Hospital Universitario Tenerife
city: Valencia
country: Spain
facility: Hospital universitari i politècnic La Fe de Valencia
Study officials:
References: