Multicenter Prospective Randomized Trial of the Effect of Rivaroxaban on Survival and Development of Complications of Portal Hypertension in Patients With Cirrhosis

NCT02643212 | Unknown Phase 3 DMC

• 1 other identifier: 2014-005523-27
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 14

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.

Conditions

Cirrhosis

Outcome Measures

Primary Outcomes (1)

• Survival free of transplant and decompensation / complications of portal hypertension.

  Is defined as decompensation / complications of portal hypertension: * significant bleeding episode (defined as Baveno V) by portal hypertension (esophageal varices, gastric varices; gastropathy Portal Hypertension) * Hepatic encephalopathy grade II or higher. * decompensation of ascites: In patients without ascites decompensation be considered the onset of clinically detectable ascites and confirmed by utrasounds de novo; whereas in those with previous ascites will be considered end-point for worsening ascites if required: a) perform two or more paracentesis evacuator in the next 6 months, or b) the completion of a Transjugular intrahepatic portosystemic shunt.

  At month 24

Secondary Outcomes (10)

• Cirrhosis progression disease (bleeding episode, encephalopathy, ascitis)

  At month 24

• Development of portal vein thrombosis detected by ultrasound and confirmed by CT angiography or MRI angiography

  At month 24

• To evaluate the efficacy in preventing complications of portal hypertension

  At month 24

• 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

  At month 24

• To evaluate the incidence of hepatocellular carcinoma

  At month 24

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Rivaroxaban

EXPERIMENTAL

Rivaroxaban 10mg, 1 once a day

Drug: Rivaroxaban

Interventions

Rivaroxaban DRUG

Rivaroxaban

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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)

Sponsors & Collaborators

• David Garcia Cinca: lead
• IDIBAPS - Dr. Juan Carlos García Pagán: collaborator

Study Sites (14)

Hospital German Trias i Pujol

Badalona, Barcelona, 08916, Spain

NOT YET RECRUITING

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

RECRUITING

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, 39008, Spain

RECRUITING

Hospital Universitario Puerta de Hierro de Majadahonda

Majadahonda, Madrid, 28222, Spain

NOT YET RECRUITING

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, 33011, Spain

RECRUITING

Hospital de la Santa Creu i Sant Pau.

Barcelona, 08025, Spain

NOT YET RECRUITING

Hospital Vall d´Hebron

Barcelona, 08035, Spain

NOT YET RECRUITING

Hospital Clínic i Provincial de Barcelona

Barcelona, 08036, Spain

RECRUITING

Hospital Arnau de Vilanova

Lleida, 25198, Spain

RECRUITING

Hospital Gregorio Marañón

Madrid, 28007, Spain

NOT YET RECRUITING

Hospital Ramón y Cajal

Madrid, 28034, Spain

RECRUITING

Complejo Hospitalario de Pontevedra_Hospital Montecelo

Pontevedra, 36471, Spain

RECRUITING

Hospital Universitario Tenerife

Santa Cruz de Tenerife, 38320, Spain

NOT YET RECRUITING

Hospital universitari i politècnic La Fe de Valencia

Valencia, 46026, Spain

NOT YET RECRUITING

Related Publications (1)

• Puente A, Turon F, Martinez J, Fortea JI, Guerra MH, Alvarado E, Pons M, Magaz M, Llop E, Alvarez-Navascues C, Navarrete AA, Berenguer M, Masnou H, Banares R, Casado M, Ampuero J, Rios J, Saavedra C, Blasi A, Lisman T, Figuero CR, Huelin P, Tellez L, Arraez DM, Rodriguez M, Aguilera V, Arias Loste MT, Baiges A, Hernandez-Gea V, Perello C, Calleja JL, Genesca J, Villanueva C, Gonzalez-Alayon C, Albillos A, Crespo J, Garcia-Pagan JC. Rivaroxaban to prevent complications of portal hypertension in cirrhosis: The CIRROXABAN study. J Hepatol. 2025 Nov;83(5):1069-1076. doi: 10.1016/j.jhep.2025.06.035. Epub 2025 Jul 19.

  PMID: 40691992 DERIVED

MeSH Terms

Conditions

Fibrosis

Interventions

Rivaroxaban

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Juan Carlos García Pagan, MD

CONTACT

+34 93 227 54 00

David Garcia Cinca

CONTACT

+34 93 227 54 00; dgarcia@clinic.ub.es

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Project Manager

Study Record Dates

• First Submitted: October 26, 2015
• First Posted: December 31, 2015
• Study Start: May 1, 2016
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: April 25, 2018

Record last verified: 2018-04

Locations

ES (14)