Anticoagulation for Advanced Cirrhotic Patients After TIPS
Primary Purpose
Liver Cirrhosis
Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Rivaroxaban
Sponsored by
About this trial
This is an interventional treatment trial for Liver Cirrhosis focused on measuring liver cirrhosis, Transjugular Intrahepatic Portosystemic Stent Shunt, Anticoagulation, Survival, Additional decompensation
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.
Sites / Locations
- The Third Affiliated Hospital of Sun Yat-sen UniversityRecruiting
- Nanfang Hospital Affiliated to Southern Medical UniversityRecruiting
- The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolRecruiting
- The first affiliated hospital of Nanchang universityRecruiting
- The First Affiliated Hospital, Air Force Medical University
- Xi'an International Medical Center HospitalRecruiting
- The First Affiliated Hospital of Xi'an Jiaotong UniversityRecruiting
- Provincial Hospital Affiliated to Shandong UniversityRecruiting
- The First Affiliated Hospital of Xinjiang Medical UniversityRecruiting
- The Second Affiliated Hospital of Kunming Medical UniversityRecruiting
- The First Affiliated Hospital of Zhejiang UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Anticoagulation
Non-anticoagulated
Arm Description
Rivaroxaban:10mg/d for 2 years
No anticoagulants will be used.
Outcomes
Primary Outcome Measures
Transplant-free survival
Secondary Outcome Measures
Number of participants with all-cause rebleeding
Number of participants with overt hepatic encephalopathy
Number of participants with recurrent or worsening ascites
Perform two or more evacuative paracentesis in the following six months
Number of participants with shunt dysfunction
Effect of anticoagulation on liver function estimated by the Child-Pugh and the model for end-stage liver disease scores
Echocardiography findings
Serum levels of bacterial translocation biomarkers and proinflammatory cytokines
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.
Compliance
Record of unused packaging and information about compliance in a patient diary
Score of Health Related Quality of Life questionnaire,for example, SF-36
Full Information
NCT ID
NCT03005444
First Posted
December 21, 2016
Last Updated
October 22, 2022
Sponsor
Air Force Military Medical University, China
1. Study Identification
Unique Protocol Identification Number
NCT03005444
Brief Title
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
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 14, 2017 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Air Force Military Medical University, China
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Cirrhosis
Keywords
liver cirrhosis, Transjugular Intrahepatic Portosystemic Stent Shunt, Anticoagulation, Survival, Additional decompensation
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
254 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Anticoagulation
Arm Type
Experimental
Arm Description
Rivaroxaban:10mg/d for 2 years
Arm Title
Non-anticoagulated
Arm Type
No Intervention
Arm Description
No anticoagulants will be used.
Intervention Type
Drug
Intervention Name(s)
Rivaroxaban
Other Intervention Name(s)
Nadroparin or Enoxaparin
Intervention Description
10mg/day, for 2 years
Primary Outcome Measure Information:
Title
Transplant-free survival
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Number of participants with all-cause rebleeding
Time Frame
2 years
Title
Number of participants with overt hepatic encephalopathy
Time Frame
2 years
Title
Number of participants with recurrent or worsening ascites
Description
Perform two or more evacuative paracentesis in the following six months
Time Frame
2 years
Title
Number of participants with shunt dysfunction
Time Frame
2 years
Title
Effect of anticoagulation on liver function estimated by the Child-Pugh and the model for end-stage liver disease scores
Time Frame
2 years
Title
Echocardiography findings
Time Frame
2 years
Title
Serum levels of bacterial translocation biomarkers and proinflammatory cytokines
Time Frame
2 years
Title
Security of anticoagulation in patients with liver cirrhosis
Description
Number of adverse events and adverse reactions in each arm of study. History and clinical evaluation of bleeding and monitoring of hematocrit.
Time Frame
2 years
Title
Compliance
Description
Record of unused packaging and information about compliance in a patient diary
Time Frame
2 years
Title
Score of Health Related Quality of Life questionnaire,for example, SF-36
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Guohong Han, MD,Ph.D
Phone
+86-13991969930
Email
13991969930@126.com
Facility Information:
Facility Name
The Third Affiliated Hospital of Sun Yat-sen University
City
Guangzhou
State/Province
Guangdong
Country
China
Individual Site Status
Recruiting
Facility Name
Nanfang Hospital Affiliated to Southern Medical University
City
Guanzhou
State/Province
Guangdong
Country
China
Individual Site Status
Recruiting
Facility Name
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
City
Nanjing
State/Province
Jiangsu
Country
China
Individual Site Status
Recruiting
Facility Name
The first affiliated hospital of Nanchang university
City
Nanchang
State/Province
Jiangxi
Country
China
Individual Site Status
Recruiting
Facility Name
The First Affiliated Hospital, Air Force Medical University
City
Xi'an
State/Province
Shaanxi
ZIP/Postal Code
710032
Country
China
Individual Site Status
Completed
Facility Name
Xi'an International Medical Center Hospital
City
Xi'an
State/Province
Shaanxi
ZIP/Postal Code
710100
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guohong Han, MD,Ph.D
Email
13991969930@126.com
First Name & Middle Initial & Last Name & Degree
Guohong Han, MD,Ph.D
First Name & Middle Initial & Last Name & Degree
Hui Chen, MD,Ph.D
Facility Name
The First Affiliated Hospital of Xi'an Jiaotong University
City
Xi'an
State/Province
Shaanxi
Country
China
Individual Site Status
Recruiting
Facility Name
Provincial Hospital Affiliated to Shandong University
City
Jinan
State/Province
Shandong
Country
China
Individual Site Status
Recruiting
Facility Name
The First Affiliated Hospital of Xinjiang Medical University
City
Ürümqi
State/Province
Xinjiang
Country
China
Individual Site Status
Recruiting
Facility Name
The Second Affiliated Hospital of Kunming Medical University
City
Kunming
State/Province
Yunnan
Country
China
Individual Site Status
Recruiting
Facility Name
The First Affiliated Hospital of Zhejiang University
City
Hangzhou
State/Province
Zhejiang
Country
China
Individual Site Status
Recruiting
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Anticoagulation for Advanced Cirrhotic Patients After TIPS
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