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Transjugular Intrahepatic Portosystemic Shunt (TIPS) for Prevention of Variceal Rebleeding in Cirrhotic Patients With Portal Vein Thrombosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Fourth Military Medical University
Sponsor:
Information provided by (Responsible Party):
Guohong Han, Fourth Military Medical University
ClinicalTrials.gov Identifier:
NCT01326949
First received: March 29, 2011
Last updated: July 25, 2014
Last verified: July 2014
  Purpose

Portal vein thrombosis (PVT) refers to an obstruction in the trunk of the portal vein. It can extend downstream to the portal branches, or upstream to the splenic and/or the mesenteric veins. The prevalence of PVT is 10-25% and incidence is about 16% in cirrhotic patients. Recent studies demonstrate that the presence of PVT is not only an independent predictor of failure to control active variceal bleeding and prevent variceal rebleeding, but also significantly associated with increased mortality in patients with liver cirrhosis.

However, in recent American Association of the Study of Liver Disease (AASLD) practice guidelines and Baveno V consensus on management of PVT in cirrhotic patients, no treatment strategies in cirrhotic patients with PVT was clearly recommended due to the absence of randomized controlled trials.


Condition Intervention
Decompensated Cirrhosis
Portal Vein Thrombosis
Bleeding Varices
Procedure: Transjugular intrahepatic portosystemic shunt (TIPS)
Procedure: ET+NSBB+AT

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Transjugular Intrahepatic Portosystemic Shunt Versus Endoscopic Treatment Combined Anticoagulation and Propranolol for Prevention of Variceal Rebleeding in Cirrhotic Patients With Portal Vein Thrombosis: A Randomized Controlled Trial

Resource links provided by NLM:


Further study details as provided by Fourth Military Medical University:

Primary Outcome Measures:
  • Number of participants with variceal rebleeding [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    Variceal rebleeding is the primary endpoint of this study. Cumulative variceal rebleeding rate is compared between the two groups.


Secondary Outcome Measures:
  • Number of death [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    Death is a secondary endpoint of this study. Cumulative survival rate is compared between the two groups.

  • Number of participants achieving portal vein recanalization [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    Portal vein recanalization is a secondary endpoint of this study. Recanalization rate of thrombosed portal vein is compared between the two groups.

  • Changes of degree of PVT in patients without portal vein recanalization [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    We also observed changes of degree of portal vein thrombosis in patients without portal vein recanalization.

  • Number of complications [ Time Frame: 4 years ] [ Designated as safety issue: No ]

    Complications include:

    TIPS-related complications: procedural complications, shunt dysfunction and hepatic encephalopathy.

    Complications related to endoscopic and drug treatment.



Estimated Enrollment: 50
Study Start Date: May 2011
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: ET+NSBB+AT

Endoscopic treatment(ET)- Endoscopic variceal ligation (EVL) and endoscopic injection.

Non-selective beta blocker(NSBB)-Propranolol.

Anticoagulation(AT)- Heparin followed by warfarin.

Procedure: ET+NSBB+AT

ET-Esophageal varices was treated by endoscopic variceal ligation (EVL). EVL was repeated at intervals of 3-4 weeks until the varices were obliterated or reduced to grade-I size. Gastric varices was treated by endoscopic injection using cyanoacrylate.

NSBB-Propranolol started at a dose of 20mg twice a day. The dose is adjusted to the maximal tolerated doses to heart rate (HR) of 55 bpm or to decrease the HR 25% from baseline.

AT-A continuously intravenous infusion of unfractionated heparin followed by oral warfarin is employed. Initially, heparin is administered intravenously at a starting dose of 1,000 U/h for 5 days. Subsequently, oral warfarin is prescribed at the dosage of 5 mg/d for 6 months and adjusted to maintain the INR at a target of 2.5 (range 2.0-3.0).

Active Comparator: TIPS
Transjugular intrahepatic portosystemic shunt(TIPS)- TIPS.
Procedure: Transjugular intrahepatic portosystemic shunt (TIPS)
Transjugular intrahepatic portosystemic shunt(TIPS)- TIPS was performed in a conventional fashion or in combination of percutaneous transhepatic or transsplenic approach. Postoperatively, intravenous heparin (8,000-12,000 u/d) for five days, warfarin for six months to one year and lifelong aspirin were routinely prescribed at dosages to achieve an international normalized ratio (INR) of up to two times the upper limit of normal for the prevention of shunt dysfunction. Intravenous arginine and branched-chain amino acids and antibiotics were administered for five days as prophylactics for encephalopathy and operation-related infection, respectively. TIPS revision was planned if any evidence of shunt dysfunction was seen; thereafter, long-term anticoagulation was prescribed.

Detailed Description:

Anticoagulation

Anticoagulation appears to be an effective first-line therapy for PVT in non-cirrhotic patients. However, anticoagulation is more complex in the setting of cirrhosis. The risk to benefit ratio of anticoagulation have never been fully confirmed in cirrhosis if there are a history of variceal bleeding or high-risk varices. Furthermore, the application of anticoagulation combined with non-selective beta-blockers and endoscopic variceal ligation is not completely advocated in cirrhotic patients with PVT due to the limited reports and the increased risk of bleeding.

Transjugular intrahepatic portosystemic shunt (TIPS)

TIPS is just regarded as the second-line therapy for the secondary prophylaxis of variceal bleeding in cirrhotic patients. However, this indication might be changed in the setting of PVT, given that an earlier decision of TIPS for PVT might achieve a higher recanalization rate. Certainly, an early decision of TIPS seemed to bring the risks of hepatic encephalopathy, liver failure, and procedural complications, although a high recanalization rate of thrombosed portal vein and prevention of variceal bleeding was achieved. Indeed, the risk to benefit ratio of TIPS in cirrhotic patients with PVT for the prevention of recurrent variceal bleeding has never been evaluated.

The aim of this study is to compare the efficacy and safety of TIPS and conventional therapy (endoscopic treatment, propranolol and anticoagulation) in decompensated cirrhosis patients with PVT and a history of variceal bleeding.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent
  • Liver cirrhosis
  • Portal vein thrombosis (degree of vessel obstruction > 50%)
  • History of variceal hemorrhage (recent variceal bleeding has been controlled for at least 120 hours)

Exclusion Criteria:

  • Active variceal bleeding
  • Fibrotic cord of the portal vein
  • Prior history of TIPS placement or shunt surgery
  • Concomitant renal insufficiency
  • Severe cardiopulmonary diseases
  • Uncontrolled systemic infection or sepsis
  • Malignancy or other serious medical illness which may reduce the life expectancy
  • Contraindications for propranolol, such as asthma, insulin-dependent diabetes (with episodes of hypoglycemia), and peripheral vascular disease
  • Contraindications for heparin or warfarin
  • Contraindications for TIPS
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01326949

Contacts
Contact: Xingshun Qi, MD 86-29-84775221 xingshunqi@126.com

Locations
China, Shaanxi
Xijing Hospital of Digestive Diseases, Fourth Military Medical University Recruiting
Xi'an, Shaanxi, China, 710032
Contact: Guohong Han, MD    86-29-84775221    hangh@fmmu.edu.cn; guohhan@126.com   
Contact: Xingshun Qi, MD    86-29-84775221    xingshunqi@126.com   
Sub-Investigator: Xingshun Qi         
Sub-Investigator: Zhanxin Yin         
Sub-Investigator: Chuangye He         
Sub-Investigator: Wengang Guo         
Sub-Investigator: Jing Niu         
Sub-Investigator: Wei Bai         
Sub-Investigator: Zhiping Yang         
Sub-Investigator: Ming Bai         
Sponsors and Collaborators
Fourth Military Medical University
Investigators
Principal Investigator: Guohong Han Xijing Hospital of Digestive Diseases, Fourth Military Medical University
  More Information

Publications:
Responsible Party: Guohong Han, Head of Department of Digestive Interventional Radiology, Fourth Military Medical University
ClinicalTrials.gov Identifier: NCT01326949     History of Changes
Other Study ID Numbers: 1PVT-TIPS
Study First Received: March 29, 2011
Last Updated: July 25, 2014
Health Authority: China: Ethics Committee

Additional relevant MeSH terms:
Liver Cirrhosis
Thrombosis
Venous Thrombosis
Cardiovascular Diseases
Digestive System Diseases
Embolism and Thrombosis
Liver Diseases
Vascular Diseases
Propranolol
Adrenergic Agents
Adrenergic Antagonists
Adrenergic beta-Antagonists
Anti-Arrhythmia Agents
Antihypertensive Agents
Cardiovascular Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on November 27, 2014