Anticoagulation for Advanced Cirrhotic Patients After TIPS

Study Overview
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Brief Summary
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Recent studies demonstrated that liver cirrhosis was associated with a hypercoagulability state. Besides, bacterial translocation plays an important role in the pathogenesis and complications in patients with decompensated cirrhosis, including infections as well as hepatic encephalopathy and hepatorenal syndrome. A recent prospective study in a group of 70 patients with liver cirrhosis (Child B and C stages up to 10 points) who were randomized to receive enoxaparin for a year (n = 34) vs no intervention (n = 36) showed that anticoagulant treatment with enoxaparin is safe and effective, significantly reducing risk of PVT development and liver decompensation, markedly improving overall survival. This study provides exciting preliminary data regarding the potential use of prophylactic anticoagulation in improving clinical outcomes in cirrhosis, beyond the prevention of portal vein thrombosis. This study suggested that the effect was partly due to a direct effect of reducing BT and levels of proinflammatory cytokines. However, this study included few patients, was not double blind, and did not have a placebo group. Therefore, despite the spectacular results, the use of prophylactic anticoagulant therapy has not become routine practice in patients with cirrhosis and more studies are needed to assess the potential usefulness of anticoagulation in improving the prognosis of liver cirrhosis. Transjugular intrahepatic portosystemic shunts (TIPS) are now routinely used to treat the complications of portal hypertension, such as variceal bleeding and refractory ascites. TIPS is the most effective method to prevent rebleeding, however, it is burdened with increased risk of hepatic encephalopathy and deterioration of liver function in patients with advanced cirrhosis. Notably, TIPS can not only relieve portal pressure but also can redirect the portal blood flow through the shunt directly into the systemic circulation which can cause systemic hemodynamic changes. Given the preliminary data suggesting a beneficial effect of prophylactic anticoagulation with LMWH in cirrhotic patients, this multicenter randomized controlled study attempts to demonstrate the effect of long term LMWH therapy after TIPS on survival in cirrhotic patients with variceal bleeding.

Official Title
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Anticoagulation for Development of Further Decompensation and Survival in Advanced Cirrhosis After Transjugular Intrahepatic Portosystemic Shunt: a Multicenter Randomized Controlled Study

Conditions
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Liver Cirrhosis

Intervention / Treatment
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* Drug: Rivaroxaban


Participation Criteria
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Eligibility Criteria
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All inclusion criteria must be met at the time of screening: Signed informed consent. Male or female patients with an age of 18 to 75 years Liver cirrhosis. History of variceal bleeding > 5 days Presence of ascites Successful TIPS Use of Viatorr stent Child-Pugh score within B7-C13 Bilirubin level of 3 mg/dL or less (51.3 umol/L) Patients who meet the following criteria at the time of screening will be excluded: Hepatocellular carcinoma or other intrahepatic/extrahepatic cancers. Spontaneous overt hepatic encephalopathy. Previous or current portal venous system thrombosis. Budd-Chiari syndrome. Known coagulation disorder besides liver cirrhosis. Severe thrombocytopenia <15,000 platelets/dl. Peptic ulcer disease in the last 6 months. Unstable angina or myocardial infarction (MI) within the past 6 months before randomization. Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted). Uncontrolled hypertension. Prior liver transplantation or candidates for liver transplantation. History of shunting surgery or TIPS before randomization. Pregnancy or breastfeeding Poor compliance Participation in another clinical trial Close affiliation with the investigational site.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anticoagulation<br>Rivaroxaban：10mg/d for 2 years | Drug: Rivaroxaban<br>* 10mg/day, for 2 years<br>* Other names: Nadroparin or Enoxaparin;|
| No Intervention: Non-anticoagulated<br>No anticoagulants will be used. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transplant-free survival |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with all-cause rebleeding |  | 2 years | 
| Number of participants with overt hepatic encephalopathy |  | 2 years | 
| Number of participants with recurrent or worsening ascites | Perform two or more evacuative paracentesis in the following six months | 2 years | 
| Number of participants with shunt dysfunction |  | 2 years | 
| Effect of anticoagulation on liver function estimated by the Child-Pugh and the model for end-stage liver disease scores |  | 2 years | 
| Echocardiography findings |  | 2 years | 
| Serum levels of bacterial translocation biomarkers and proinflammatory cytokines |  | 2 years | 
| Security of anticoagulation 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. | 2 years | 
| Compliance | Record of unused packaging and information about compliance in a patient diary | 2 years | 
| Score of Health Related Quality of Life questionnaire，for example, SF-36 |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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liver cirrhosis, Transjugular Intrahepatic Portosystemic Stent Shunt, Anticoagulation, Survival, Additional decompensation