Multicenter prospective randomized trial of the effect of rivaroxaban on survival and development of complications of portal hypertension in patients with cirrhosis
- Conditions
- iver cirrhosisTherapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- EUCTR2014-005523-27-ES
- Lead Sponsor
- INSTITUTO DE INVESTIGACIONES BIOMEDICAS AUGUST PI I SUNYER (IDIBAPS)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 160
a. Aged between 18 and 75 years of both sexes.
b. Clinical and / or laboratory criteria, ultrasound and / or liver biopsy compatible with the diagnosis of viral cirrhosis (If HBV: HBV-DNA must be negative; if HCV: SVR 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); NASH and cryptogenic.
c. Presence of clinically significant portal hypertension (CSPHT) defined by clinical criteria (presence of esophageal varices or ascites), elastography (liver Fibroscan® ? 21 kPa) or hemodynamic (HVPG ? 10 mmHg)
d. Mild to moderate hepatic impairment defined by Child-Pugh of 7-10 points.
e. Written informed consent to participate in the study
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 160
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 160
a. Any previous or current thrombosis in splenoportal axis (must be ruled out by US-Doppler earlier than one month after randomization; if doubts: AngioCT or AngioMRI if required).
b. Background of hepatic encephalopathy grade II or higher
c. Ascites that required prior practice of paracentesis in the last year
d. Indication for use of anticoagulant and / or antiplatelet therapy for any reason.
e. Hypersensitivity to the active ingredient or to excipients
f. Active bleeding, clinically significant, or risk of major bleeding.
g. Pregnancy and lactation.
h. HCC or malignant neoplasia at the time of inclusion.
i. Any comorbidity involving a therapeutic limitation and/or a life expectancy <12 months.
j. Existence of risk bleeding esophageal varices or prior variceal bleeding. They may not be included untill full treatment (stable beta blockers dosage or eradication trough varices ligation).
k. Pregnancy or lactation.
l. Severe thrombocytopenia <40,000 platelets / dl.
m. Kidney failure (creatinine clearance <15ml / min).
n. TIPS or portosystemic shunt carrier.
o. Child-Pugh score greater than 10.
p. In HCV liver cirrosis patients: not carrying at least six months in SVR. In HBV liver cirrosis patients: HBV DNA is not negative .
q. Active alcoholism (60 g / day in men and 40 in women)
r. Use of potent inhibitors of cytochrome CYP450 3A4 (ketoconazole, protease inhibitor antiretroviral treatment in HIV patients) or cytochrome inductors (rifampicin. Phenytoin ...).
s. Participation in another clinical trial
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Survival free of: transplant and decompensations / complications of PHT.;Secondary Objective: 1. To evaluate the efficacy in preventing portal thrombosis (PT).<br>2. To evaluate the efficacy in preventing complications of portal hypertension (PHT)<br>3. To evaluate the safety of rivaroxaban in patients with liver cirrhosis (LC)<br>4. To evaluate the incidence of HCC.<br>5. To assess the effect on liver fibrosis by non-invasive methods.<br>6. To evaluate the effect on hepatocellular function (Child-Pugh and MELD)<br>7. To correlate levels of anti-Xa and Rivaroxaban on efficacy and safety<br>8. To evaluate the effect of Rivaroxaban on HVPG (in a Substudy: CIRROXABAN-CATSHEP, in 65 patients).<br>9. To assess if Rivaroxaban reduces bacterial translocation and proinflammatory cytokines. Correlation with clinical findings.;Primary end point(s): 1. Survival free of transplant.;Timepoint(s) of evaluation of this end point: At month 24
- Secondary Outcome Measures
Name Time Method