Clinical trial NCT03005444: Anticoagulation for Advanced Cirrhotic Patients After TIPS
Official title: Anticoagulation for Development of Further Decompensation and Survival in Advanced Cirrhosis After Transjugular Intrahepatic Portosystemic Shunt: a Multicenter Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Liver Cirrhosis
Keywords: liver cirrhosis
Transjugular Intrahepatic Portosystemic Stent Shunt
Anticoagulation
Survival
Additional decompensation
Lead sponsor: Air Force Military Medical University, China
Sponsor class: OTHER
First posted: 2016-12-29
Enrollment: 254
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Transplant-free survival
timeFrame: 2 years
Secondary outcomes:
measure: Number of participants with all-cause rebleeding
timeFrame: 2 years
measure: Number of participants with overt hepatic encephalopathy
timeFrame: 2 years
measure: Number of participants with recurrent or worsening ascites
timeFrame: 2 years
measure: Number of participants with shunt dysfunction
timeFrame: 2 years
measure: Effect of anticoagulation on liver function estimated by the Child-Pugh and the model for end-stage liver disease scores
timeFrame: 2 years
measure: Echocardiography findings
timeFrame: 2 years
measure: Serum levels of bacterial translocation biomarkers and proinflammatory cytokines
timeFrame: 2 years
measure: Security of anticoagulation in patients with liver cirrhosis
timeFrame: 2 years
measure: Compliance
timeFrame: 2 years
measure: Score of Health Related Quality of Life questionnaire，for example, SF-36
timeFrame: 2 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The Third Affiliated Hospital of Sun Yat-sen University
state: Guangdong
city: Guanzhou
country: China
facility: Nanfang Hospital Affiliated to Southern Medical University
state: Guangdong
city: Nanjing
country: China
facility: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
state: Jiangsu
city: Nanchang
country: China
facility: The first affiliated hospital of Nanchang university
state: Jiangxi
city: Xi'an
country: China
facility: The First Affiliated Hospital, Air Force Medical University
state: Shaanxi
city: Xi'an
country: China
facility: Xi'an International Medical Center Hospital
state: Shaanxi
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Jinan
country: China
facility: Provincial Hospital Affiliated to Shandong University
state: Shandong
city: Ürümqi
country: China
facility: The First Affiliated Hospital of Xinjiang Medical University
state: Xinjiang
city: Kunming
country: China
facility: The Second Affiliated Hospital of Kunming Medical University
state: Yunnan
city: Hangzhou
country: China
facility: The First Affiliated Hospital of Zhejiang University
state: Zhejiang
Study officials:
References: