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Anticoagulation for Advanced Cirrhotic Patients After TIPS

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ClinicalTrials.gov Identifier: NCT03005444
Recruitment Status : Recruiting
First Posted : December 29, 2016
Last Update Posted : April 23, 2019
Sponsor:
Information provided by (Responsible Party):
Guohong Han, Fourth Military Medical University

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.


Condition or disease Intervention/treatment Phase
Liver Cirrhosis Drug: Rivaroxaban Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 254 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Anticoagulation for Development of Further Decompensation and Survival in Advanced Cirrhosis After Transjugular Intrahepatic Portosystemic Shunt: a Multicenter Randomized Controlled Study
Actual Study Start Date : June 14, 2017
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cirrhosis
Drug Information available for: Rivaroxaban

Arm Intervention/treatment
Experimental: Anticoagulation
Rivaroxaban:10mg/d for 2 years
Drug: Rivaroxaban
10mg/day, for 2 years
Other Name: Nadroparin or Enoxaparin

No Intervention: Non-anticoagulated
No anticoagulants will be used.



Primary Outcome Measures :
  1. Transplant-free survival [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Number of participants with all-cause rebleeding [ Time Frame: 2 years ]
  2. Number of participants with overt hepatic encephalopathy [ Time Frame: 2 years ]
  3. Number of participants with recurrent or worsening ascites [ Time Frame: 2 years ]
    Perform two or more evacuative paracentesis in the following six months

  4. Number of participants with shunt dysfunction [ Time Frame: 2 years ]
  5. Effect of anticoagulation on liver function estimated by the Child-Pugh and the model for end-stage liver disease scores [ Time Frame: 2 years ]
  6. Echocardiography findings [ Time Frame: 2 years ]
  7. Serum levels of bacterial translocation biomarkers and proinflammatory cytokines [ Time Frame: 2 years ]
  8. Security of anticoagulation in patients with liver cirrhosis [ Time Frame: 2 years ]
    Number of adverse events and adverse reactions in each arm of study. History and clinical evaluation of bleeding and monitoring of hematocrit.

  9. Compliance [ Time Frame: 2 years ]
    Record of unused packaging and information about compliance in a patient diary

  10. Score of Health Related Quality of Life questionnaire,for example, SF-36 [ Time Frame: 2 years ]


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03005444


Contacts
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Contact: Guohong Han, MD,Ph.D +86-29-84771537 hangh@fmmu.edu.cn

Locations
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China, Guangdong
The Third Affiliated Hospital of Sun Yat-sen University Not yet recruiting
Guangzhou, Guangdong, China
Nanfang Hospital Affiliated to Southern Medical University Not yet recruiting
Guanzhou, Guangdong, China
China, Jiangsu
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School Not yet recruiting
Nanjing, Jiangsu, China
China, Jiangxi
The first affiliated hospital of Nanchang university Not yet recruiting
Nanchang, Jiangxi, China
China, Shaanxi
Xijing Hospital of digestive disease, Fourth Military Medical University Recruiting
Xi'an, Shaanxi, China, 710032
Contact: Guohong Han, MD,Ph.D       hangh@fmmu.edu.cn   
Principal Investigator: Guohong Han, MD,Ph.D         
Sub-Investigator: Hui Chen, MD,Ph.D         
The First Affiliated Hospital of Xi'an Jiaotong University Not yet recruiting
Xi'an, Shaanxi, China
China, Shandong
Provincial Hospital Affiliated to Shandong University Not yet recruiting
Jinan, Shandong, China
China, Xinjiang
The First Affiliated Hospital of Xinjiang Medical University Not yet recruiting
Ürümqi, Xinjiang, China
China, Yunnan
The Second Affiliated Hospital of Kunming Medical University Not yet recruiting
Kunming, Yunnan, China
China, Zhejiang
The First Affiliated Hospital of Zhejiang University Not yet recruiting
Hangzhou, Zhejiang, China
Sponsors and Collaborators
Fourth Military Medical University

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Responsible Party: Guohong Han, MD, Fourth Military Medical University
ClinicalTrials.gov Identifier: NCT03005444     History of Changes
Other Study ID Numbers: APPROACH
First Posted: December 29, 2016    Key Record Dates
Last Update Posted: April 23, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Guohong Han, Fourth Military Medical University:
liver cirrhosis
Transjugular Intrahepatic Portosystemic Stent Shunt
Anticoagulation
Survival
Additional decompensation

Additional relevant MeSH terms:
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Liver Cirrhosis
Fibrosis
Pathologic Processes
Liver Diseases
Digestive System Diseases
Rivaroxaban
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants