Anticoagulation for Advanced Cirrhotic Patients After TIPS

Air Force Military Medical University of People's Liberation Army

Status

Enrolling

Conditions

Liver Cirrhosis

Treatments

Drug: Rivaroxaban

Study type

Interventional

Funder types

Other

Identifiers

NCT03005444

APPROACH

Details and patient eligibility

About

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.

Enrollment

254 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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.