Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02643212
Recruitment Status : Recruiting
First Posted : December 31, 2015
Last Update Posted : April 25, 2018
Sponsor:
Collaborator:
IDIBAPS - Dr. Juan Carlos García Pagán
Information provided by (Responsible Party):
David Garcia Cinca, Hospital Clinic of Barcelona

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.

Condition or disease Intervention/treatment Phase
Cirrhosis Drug: Rivaroxaban Drug: Placebo Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Actual Study Start Date : May 2016
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cirrhosis
Drug Information available for: Rivaroxaban

Arm Intervention/treatment
Placebo Comparator: Placebo Drug: Placebo
Experimental: Rivaroxaban
Rivaroxaban 10mg, 1 once a day
Drug: Rivaroxaban



Primary Outcome Measures :
  1. Survival free of transplant and decompensation / complications of portal hypertension. [ Time Frame: At month 24 ]

    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.


Secondary Outcome Measures :
  1. Cirrhosis progression disease (bleeding episode, encephalopathy, ascitis) [ Time Frame: At month 24 ]
    1. Bleeding episode due to portal hypertension.
    2. Hepatic encephalopathy grade II or higher.
    3. Ascitic decompensation: In patients without ascites, decompensation defined as "de novo" clinically detectable ascites; whereas in those with previous ascites is considered end-point for worsening ascites if required: a) perform two or more evacuative paracentesis in the following six months, or b) the completion of a TIPS

  2. Development of portal vein thrombosis detected by ultrasound and confirmed by CT angiography or MRI angiography [ Time Frame: At month 24 ]
  3. To evaluate the efficacy in preventing complications of portal hypertension [ Time Frame: At month 24 ]
    Development of complications of portal hypertension (anamnesis, physical examination, ultrasound and fibrogastroscopy)

  4. 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 [ Time Frame: At month 24 ]
    Evaluate number of bleeding episodes, hematocrit values and number of adverse events and reactions.

  5. To evaluate the incidence of hepatocellular carcinoma [ Time Frame: At month 24 ]
    Incidence of hepatocellular carcinoma by semiannual ultrasound.

  6. Effect on splenic and liver elasticity measured by fibroscan and / or acoustic radiation force impulse. [ Time Frame: At month 24 ]
    Effect of rivaroxaban on liver fibrosis assessed by liver elastography measured by fibroscan and / or acoustic radiation force impulse at baseline and every six months conditions.

  7. Effect of Rivaroxaban on hepatocellular function estimated by the Child-Pugh and the model for end-stage liver disease scores. [ Time Frame: At month 24 ]
  8. 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. [ Time Frame: At month 24 ]
    To correlate levels of Rivaroxaban and anti-factor Xa to the efficacy and safety of the drug. Rivaroxaban

  9. To evaluate the effect of Rivaroxaban on hepatic venous pressure gradient [ Time Frame: At month 24 ]
    Effect on hepatic venous pressure gradient. Determination of hepatic venous pressure gradient at baseline and 12 months rivaroxaban or placebo

  10. To assess if Rivaroxaban reduces concentration of intestinal fatty acid binding protein, 16S ribosomal DNA, CD14, interleukin 6, lipopolysaccharide binding protein and lipopolysaccharide [ Time Frame: At month 24 ]
    Assess Rivaroxaban reduces bacterial translocation and proinflammatory cytokines. Correlation with clinical events.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02643212


Contacts
Layout table for location contacts
Contact: Juan Carlos García Pagan, MD +34 93 227 54 00
Contact: David Garcia Cinca +34 93 227 54 00 dgarcia@clinic.ub.es

Locations
Layout table for location information
Spain
Hospital Universitario Central de Asturias Recruiting
Oviedo, Asturias, Spain, 33011
Principal Investigator: Carmen Alvarez-Navascués         
Hospital German Trias i Pujol Not yet recruiting
Badalona, Barcelona, Spain, 08916
Principal Investigator: Betty Paola Morales         
Hospital Universitari de Bellvitge Recruiting
Hospitalet de Llobregat, Barcelona, Spain, 08907
Principal Investigator: José Castellote         
Hospital Universitario Marqués de Valdecilla Recruiting
Santander, Cantabria, Spain, 39008
Principal Investigator: Angela Puente         
Hospital Universitario Puerta de Hierro de Majadahonda Not yet recruiting
Majadahonda, Madrid, Spain, 28222
Principal Investigator: José Luis Calleja         
Hospital de la Santa Creu i Sant Pau. Not yet recruiting
Barcelona, Spain, 08025
Principal Investigator: Càndid Villanueva         
Hospital Vall d´Hebron Not yet recruiting
Barcelona, Spain, 08035
Principal Investigator: Joan Genescà         
Hospital Clínic i Provincial de Barcelona Recruiting
Barcelona, Spain, 08036
Principal Investigator: Juan Carlos Garcia-Pagan, MD         
Hospital Arnau de Vilanova Recruiting
Lérida, Spain, 25198
Principal Investigator: Carles Aracil         
Hospital Gregorio Marañón Not yet recruiting
Madrid, Spain, 28007
Principal Investigator: Rafael Bañares         
Hospital Ramón y Cajal Recruiting
Madrid, Spain, 28034
Principal Investigator: Agustin Albillos         
Complejo Hospitalario de Pontevedra_Hospital Montecelo Recruiting
Pontevedra, Spain, 36471
Principal Investigator: Juan Turnes         
Hospital Universitario Tenerife Not yet recruiting
Tenerife, Spain, 38320
Principal Investigator: Manuel Hernández-Guerra de Aguilar         
Hospital universitari i politècnic La Fe de Valencia Not yet recruiting
Valencia, Spain, 46026
Principal Investigator: María Berenguer         
Sponsors and Collaborators
David Garcia Cinca
IDIBAPS - Dr. Juan Carlos García Pagán

Layout table for additonal information
Responsible Party: David Garcia Cinca, Project Manager, Hospital Clinic of Barcelona
ClinicalTrials.gov Identifier: NCT02643212     History of Changes
Other Study ID Numbers: 2014-005523-27
First Posted: December 31, 2015    Key Record Dates
Last Update Posted: April 25, 2018
Last Verified: April 2018
Additional relevant MeSH terms:
Layout table for MeSH terms
Liver Cirrhosis
Fibrosis
Pathologic Processes
Liver Diseases
Digestive System Diseases
Rivaroxaban
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants