CirrhosisPhase 3CIRROXABANNCT02643212
Multicenter Prospective Randomized Trial of the Effect of Rivaroxaban on Survival and Development of Complications of Portal Hypertension in Patients With Cirrhosis
A Phase 3 study testing Rivaroxaban in people with Cirrhosis, run by David Garcia Cinca at 14 sites in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Cirrhosis
- What is being tested?
- Rivaroxaban
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- 14 sitesSpain
- Study dates
- May 2016to Dec 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 18Show fewer
- 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
Trial locations and contacts
14 sites in 1 country.
Juan Carlos García Pagan, MD contact
14 sites in 1 country
Spain14 sites, 14 recruiting
- Not yet recruiting
Hospital German Trias i Pujol
Badalona, Barcelona, 08916
Betty Paola Morales
- Not yet recruiting
Hospital de la Santa Creu i Sant Pau.
Barcelona, 08025
Càndid Villanueva
- Not yet recruiting
Hospital Vall d´Hebron
Barcelona, 08035
Joan Genescà
- Recruiting
Hospital Clínic i Provincial de Barcelona
Barcelona, 08036
Juan Carlos Garcia-Pagan, MD
- Recruiting
Hospital Universitari de Bellvitge
L'Hospitalet de Llobregat, Barcelona, 08907
José Castellote
- Recruiting
Hospital Arnau de Vilanova
Lleida, 25198
Carles Aracil
- Not yet recruiting
Hospital Gregorio Marañón
Madrid, 28007
Rafael Bañares
- Recruiting
Hospital Ramón y Cajal
Madrid, 28034
Agustin Albillos
- Not yet recruiting
Hospital Universitario Puerta de Hierro de Majadahonda
Majadahonda, Madrid, 28222
José Luis Calleja
- Recruiting
Hospital Universitario Central de Asturias
Oviedo, Principality of Asturias, 33011
Carmen Alvarez-Navascués
- Recruiting
Complejo Hospitalario de Pontevedra_Hospital Montecelo
Pontevedra, 36471
Juan Turnes
- Not yet recruiting
Hospital Universitario Tenerife
Santa Cruz de Tenerife, 38320
Manuel Hernández-Guerra de Aguilar
- Recruiting
Hospital Universitario Marqués de Valdecilla
Santander, Cantabria, 39008
Angela Puente
- Not yet recruiting
Hospital universitari i politècnic La Fe de Valencia
Valencia, 46026
María Berenguer
About this study
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
- Being tested
- Rivaroxaban, Placebo
- Medical subject headings
- Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RivaroxabanDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
| Rivaroxaban | Experimental | Rivaroxaban 10mg, 1 once a day Receives: Drug: Rivaroxaban |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At month 24
Secondary outcomes (10)
Cirrhosis progression disease (bleeding episode, encephalopathy, ascitis)
- Bleeding episode due to portal hypertension.
- Hepatic encephalopathy grade II or higher.
- 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
Measured: At month 24
Development of portal vein thrombosis detected by ultrasound and confirmed by CT angiography or MRI angiography
Measured: At month 24
To evaluate the efficacy in preventing complications of portal hypertension
Development of complications of portal hypertension (anamnesis, physical examination, ultrasound and fibrogastroscopy)
Measured: 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
Evaluate number of bleeding episodes, hematocrit values and number of adverse events and reactions.
Measured: At month 24
To evaluate the incidence of hepatocellular carcinoma
Incidence of hepatocellular carcinoma by semiannual ultrasound.
Measured: At month 24
Effect on splenic and liver elasticity measured by fibroscan and / or acoustic radiation force impulse.
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.
Measured: At month 24
Effect of Rivaroxaban on hepatocellular function estimated by the Child-Pugh and the model for end-stage liver disease scores.
Measured: At month 24
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.
To correlate levels of Rivaroxaban and anti-factor Xa to the efficacy and safety of the drug. Rivaroxaban
Measured: At month 24
To evaluate the effect of Rivaroxaban on hepatic venous pressure gradient
Effect on hepatic venous pressure gradient. Determination of hepatic venous pressure gradient at baseline and 12 months rivaroxaban or placebo
Measured: At month 24
To assess if Rivaroxaban reduces concentration of intestinal fatty acid binding protein, 16S ribosomal DNA, CD14, interleukin 6, lipopolysaccharide binding protein and lipopolysaccharide
Assess Rivaroxaban reduces bacterial translocation and proinflammatory cytokines. Correlation with clinical events.
Measured: At month 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Dec 2015 (estimated)
- Study startMay 2016
- Primary completionDec 2019 (estimated)
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CirrhosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- David Garcia Cinca
- Sponsor type
- University, hospital or other
- Collaborators
- IDIBAPS - Dr. Juan Carlos García Pagán
- Responsible party
- Sponsor-investigator, David Garcia Cinca, Hospital Clinic of Barcelona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02643212
- Sponsor's protocol ID
- 2014-005523-27
- Other IDs
- 2014
- Acronym
- CIRROXABAN
- Status last verified
- Apr 2018
- First submitted
- 26 Oct 2015
- Last updated
- 25 Apr 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 40691992
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Prospective Randomized Trial of the Effect of Rivaroxaban on Survival and Development of Complications of Portal Hypertension in Patients With Cirrhosis
- ClinicalTrials.gov ID
- NCT02643212
- Acronym / sponsor ID
- CIRROXABAN / 2014-005523-27
- Conditions
- Cirrhosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- David Garcia CincaUniversity, hospital or other
- Collaborators
- IDIBAPS - Dr. Juan Carlos García Pagán
- Study start
- May 2016 (actual)
- Primary completion
- Dec 2019 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 31 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo |
| Rivaroxaban | Experimental | Drug: RivaroxabanRivaroxaban 10mg, 1 once a day |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rivaroxaban | Drug | Rivaroxaban |
| Placebo | Drug | Placebo |
Primary outcome
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.
10 secondary outcomes
Cirrhosis progression disease (bleeding episode, encephalopathy, ascitis)
Time frame: At month 24
Development of portal vein thrombosis detected by ultrasound and confirmed by CT angiography or MRI angiography
Time frame: At month 24
To evaluate the efficacy in preventing complications of portal hypertension
Time frame: 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
Time frame: At month 24
To evaluate the incidence of hepatocellular carcinoma
Time frame: At month 24
Effect on splenic and liver elasticity measured by fibroscan and / or acoustic radiation force impulse.
Time frame: At month 24
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
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 evaluate the effect of Rivaroxaban on hepatic venous pressure gradient
Time frame: At month 24
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2018.
- Derived from this study: PubMed 40691992Puente 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Juan Carlos García Pagan, MD contact
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rivaroxaban in people with Cirrhosis, run by David Garcia Cinca at 14 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Juan Carlos García Pagan, MD (+34 93 227 54 00), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival free of transplant and decompensation / complications of portal hypertension. (time frame: At month 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02643212, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2018.