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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

Tracking Information
First Submitted Date  ICMJE December 21, 2016
First Posted Date  ICMJE December 29, 2016
Last Update Posted Date April 23, 2019
Actual Study Start Date  ICMJE June 14, 2017
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 24, 2016)
Transplant-free survival [ Time Frame: 2 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03005444 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 22, 2019)
  • Number of participants with all-cause rebleeding [ Time Frame: 2 years ]
  • Number of participants with overt hepatic encephalopathy [ Time Frame: 2 years ]
  • Number of participants with recurrent or worsening ascites [ Time Frame: 2 years ]
    Perform two or more evacuative paracentesis in the following six months
  • Number of participants with shunt dysfunction [ Time Frame: 2 years ]
  • Effect of anticoagulation on liver function estimated by the Child-Pugh and the model for end-stage liver disease scores [ Time Frame: 2 years ]
  • Echocardiography findings [ Time Frame: 2 years ]
  • Serum levels of bacterial translocation biomarkers and proinflammatory cytokines [ Time Frame: 2 years ]
  • 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.
  • Compliance [ Time Frame: 2 years ]
    Record of unused packaging and information about compliance in a patient diary
  • Score of Health Related Quality of Life questionnaire,for example, SF-36 [ Time Frame: 2 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 24, 2016)
  • Number of participants with all-cause rebleeding [ Time Frame: 2 years ]
  • Number of participants with overt hepatic encephalopathy [ Time Frame: 2 years ]
  • Number of participants with "de novo" clinically detectable ascites or worsening ascites [ Time Frame: 2 years ]
  • Number of participants with shunt dysfunction [ Time Frame: 2 years ]
  • Number of participants with hepatocellular carcinoma [ Time Frame: 2 years ]
  • Effect of anticoagulation on liver function estimated by the Child-Pugh and the model for end-stage liver disease scores [ Time Frame: 2 years ]
  • Number of participants with post-TIPS liver failure [ Time Frame: 2 years ]
  • Echocardiography findings [ Time Frame: 2 years ]
  • Serum levels of bacterial translocation biomarkers and proinflammatory cytokines [ Time Frame: 2 years ]
  • Effect on liver elasticity measured by fibroscan [ Time Frame: 2 years ]
  • 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.
  • Compliance [ Time Frame: 2 years ]
    Record of unused packaging and information about compliance in a patient diary
  • Score of Health Related Quality of Life questionnaire,for example, SF-36 [ Time Frame: 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Anticoagulation for Advanced Cirrhotic Patients After TIPS
Official Title  ICMJE Anticoagulation for Development of Further Decompensation and Survival in Advanced Cirrhosis After Transjugular Intrahepatic Portosystemic Shunt: a Multicenter Randomized Controlled Study
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Liver Cirrhosis
Intervention  ICMJE Drug: Rivaroxaban
10mg/day, for 2 years
Other Name: Nadroparin or Enoxaparin
Study Arms  ICMJE
  • Experimental: Anticoagulation
    Rivaroxaban:10mg/d for 2 years
    Intervention: Drug: Rivaroxaban
  • No Intervention: Non-anticoagulated
    No anticoagulants will be used.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 24, 2016)
254
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2020
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Guohong Han, MD,Ph.D +86-29-84771537 hangh@fmmu.edu.cn
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03005444
Other Study ID Numbers  ICMJE APPROACH
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Guohong Han, Fourth Military Medical University
Study Sponsor  ICMJE Fourth Military Medical University
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Fourth Military Medical University
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP