Anticoagulation for Advanced Cirrhotic Patients After TIPS

NCT03005444 | Unknown

• 1 other identifier: APPROACH
• Study Type: interventional
• Target: 254
• Locations: 1 country
• Sites: 11

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.

Conditions

Liver Cirrhosis

Keywords

liver cirrhosis; Transjugular Intrahepatic Portosystemic Stent Shunt; Anticoagulation; Survival; Additional decompensation

Outcome Measures

Primary Outcomes (1)

• Transplant-free survival

  2 years

Secondary Outcomes (10)

• Number of participants with all-cause rebleeding

  2 years

• Number of participants with overt hepatic encephalopathy

  2 years

• Number of participants with recurrent or worsening ascites

  2 years

• Number of participants with shunt dysfunction

  2 years

• Effect of anticoagulation on liver function estimated by the Child-Pugh and the model for end-stage liver disease scores

  2 years

Study Arms (2)

Anticoagulation

EXPERIMENTAL

Rivaroxaban：10mg/d for 2 years

Drug: Rivaroxaban

Non-anticoagulated

NO INTERVENTION

No anticoagulants will be used.

Interventions

Rivaroxaban DRUG

10mg/day, for 2 years

Also known as: Nadroparin or Enoxaparin

Anticoagulation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

Sponsors & Collaborators

• Air Force Military Medical University, China: lead

Study Sites (11)

The Third Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, China

RECRUITING

Nanfang Hospital Affiliated to Southern Medical University

Guanzhou, Guangdong, China

RECRUITING

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Nanjing, Jiangsu, China

RECRUITING

The first affiliated hospital of Nanchang university

Nanchang, Jiangxi, China

RECRUITING

The First Affiliated Hospital, Air Force Medical University

Xi'an, Shaanxi, 710032, China

COMPLETED

Xi'an International Medical Center Hospital

Xi'an, Shaanxi, 710100, China

RECRUITING

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, China

RECRUITING

Provincial Hospital Affiliated to Shandong University

Jinan, Shandong, China

RECRUITING

The First Affiliated Hospital of Xinjiang Medical University

Ürümqi, Xinjiang, China

RECRUITING

The Second Affiliated Hospital of Kunming Medical University

Kunming, Yunnan, China

RECRUITING

The First Affiliated Hospital of Zhejiang University

Hangzhou, Zhejiang, China

RECRUITING

MeSH Terms

Conditions

Liver Cirrhosis

Interventions

Rivaroxaban; Nadroparin; Enoxaparin

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Central Study Contacts

Guohong Han, MD,Ph.D

CONTACT

+86-13991969930; 13991969930@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD，PhD，Professor

Study Record Dates

• First Submitted: December 21, 2016
• First Posted: December 29, 2016
• Study Start: June 14, 2017
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2024
• Last Updated: October 25, 2022

Record last verified: 2022-10

Locations

CN (11)