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

Study Overview
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Brief Summary
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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, no treatment strategies in cirrhotic patients with PVT was clearly recommended due to the absence of randomized controlled trials.

Detailed Description
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Usually, cirrhotic patients with PVT are submitted to variceal rebleeding prophylaxis with endoscopic band ligation combined with non-selective beta-blockers and, when necessary, the anticoagulation is started after the varices eradication. 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. 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 endoscopic band ligation + propranolol in decompensated cirrhosis patients with PVT and a history of variceal bleeding in the past 6 weeks.

Official Title
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Transjugular Intrahepatic Portosystemic Shunt Versus Endoscopic Treatment Combined With Propranolol for Prevention of Variceal Rebleeding in Cirrhotic Patients With Portal Vein Thrombosis: A Randomized Controlled Trial

Conditions
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Decompensated Cirrhosis, Portal Vein Thrombosis, Bleeding Varices

Intervention / Treatment
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* Procedure: Transjugular intrahepatic portosystemic shunt (TIPS)
* Procedure: ET+NSBB


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Liver cirrhosis Portal vein thrombosis (degree of vessel obstruction > 50%) History of variceal hemorrhage in the past 6 weeks (recent variceal bleeding has been controlled for at least 120 hours) Exclusion Criteria: Uncontrolled active variceal bleeding Fibrotic cord of the portal vein Prior history of TIPS placement or shunt surgery or endoscopic ban ligation +NSBB 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ET+NSBB<br>Endoscopic treatment(ET)- Endoscopic variceal ligation (EVL) Non-selective beta blocker(NSBB)-Propranolol. Anticoagulation(AT)- Heparin followed by warfarin. | Procedure: ET+NSBB<br>* ET-Esophageal varices was treated by endoscopic variceal ligation (EVL). EVL was repeated at intervals of 1-2 weeks until the varices were obliterated or reduced to grade-I size. 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 for 5 days. Subsequently, oral warfarin is prescribed at the dosage of 2.5 mg/d for 6 months or until complete portal vein recanalization and adjusted to maintain the INR at a target of 2.5 (range 2.0-3.0).<br>|
| Active Comparator: TIPS<br>Transjugular intrahepatic portosystemic shunt(TIPS)- TIPS. | Procedure: Transjugular intrahepatic portosystemic shunt (TIPS)<br>* 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 were given.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with variceal rebleeding | Variceal rebleeding is the primary endpoint of this study. Cumulative variceal rebleeding rate is compared between the two groups. | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of death | Death is a secondary endpoint of this study. Cumulative survival rate is compared between the two groups. | 4 years | 
| Number of participants achieving portal vein recanalization | Portal vein recanalization is a secondary endpoint of this study. Recanalization rate of thrombosed portal vein is compared between the two groups. | 4 years | 
| Changes of degree of PVT in patients without portal vein recanalization | We also observed changes of degree of portal vein thrombosis in patients without portal vein recanalization. | 4 years | 
| Number of complications | Complications include: TIPS-related complications: procedural complications, shunt dysfunction and hepatic encephalopathy. Complications related to endoscopic and drug treatment. | 4 years |