TIPS for Variceal Rebleeding in Cirrhotic Patients With Occlusive Portal Vein Thrombosis and CTPV

Study Overview
=================
Brief Summary
-----------------
To date, there is no treatment strategies for these patients according to American Association of the Study of Liver Disease (AASLD) practice guidelines and Baveno V consensus. Thus, we aim to compare the safety and efficacy of TIPS and conservative treatment (non-selective beta blockers, endoscopic therapy and/or anticoagulation) in patients with PVT and CPTV.

Detailed Description
-----------------
The incidence of portal vein thrombosis (PVT) is about 16% in cirrhotic patients. Chronic PVT often cause two main undesirable consequences: symptomatic portal hypertension (such as variceal bleeding or ascites) and cavernous transformation of portal vein (CPTV). The former could lead to death and the latter increases the difficulty of the transjugular intrahepatic portosystemic shunt (TIPS) treatment, which is considered as a main effective treatment for symptomatic portal hypertension. Some patients with CPTV and variceal bleeding only have to receive conservative treatment (non-selective beta blockers, endoscopic therapy and/or anticoagulation). With advances in technology, modified TIPS procedure could significantly improve the operation success rate of patients with CPTV. To date, the difference in safety and efficacy between TIPS and conservative treatment (non-selective beta blockers, endoscopic therapy and/or anticoagulation) in patients with PVT and CPTV is still unclear.

Official Title
-----------------
Transjugular Intrahepatic Portosystemic Shunt (TIPS) for Variceal Rebleeding in Cirrhotic Patients With Occlusive Portal Vein Thrombosis (PVT) and Cavernous Transformation of the Portal Vein (CTPV)

Conditions
-----------------
Portal Vein, Cavernous Transformation of, Portal Vein Thrombosis, Liver Cirrhosis, Bleeding Esophageal Varices

Intervention / Treatment
-----------------
* Procedure: TIPS
* Drug: Propranolol
* Procedure: Endoscopic therapy
* Drug: Warfarin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All patients diagnosis with portal vein thrombosis and cavernous transformation of portal vein and portal hypertension by contrast enhanced CT or MRI. History of variceal bleeding. Liver cirrhosis. Neutrophilous counts≥ 1.5×109/L, Platelet counts ≥ 50 × 109/L, Hemoglobin≥ 85g/L. Albumin ≥2.8 g/dL, total bilirubin <51.3 umol/L; alanine aminotransferase (ALT) and aspartate transaminase（AST）<5 times of upper limit. PT(Prothrombin time)-INR(international normalized ratio) < 1.7. Exclusion Criteria: Thrombosis involve superior mesenteric vein, splenic vein, or the whole portal vein system. Not suitable for TIPS (judged by principal investigator). Company with malignant tumors in liver or other organs. Patients with known severe dysfunction of heart, lung, brain or kidney. Active bleeding. Not eligible for anticoagulation therapy,non-selective beta blockers or endoscopic therapy. Uncontrolled infection. Pregnancy and breastfeeding. HIV infection.

Ages Eligible for Study
-----------------
Minimum Age: 14 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TIPS arm<br>Transjugular intrahepatic portosystemic shunt(TIPS) is an artificial channel within the liver that establishes communication between the inflow portal vein and the outflow hepatic vein. It is used to treat portal hypertension.TIPS was performed in a conventional fashion or in combination of percutaneous transhepatic or transsplenic approach (also called p-TIPS or modified TIPS). Oral warfarin was used for six months to one year 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. | Procedure: TIPS<br>* Transjugular intrahepatic portosystemic shunt(TIPS)- TIPS was performed in a conventional fashion or in combination of percutaneous transhepatic or transsplenic approach (p-TIPS). Oral warfarin was used for six months to one year 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.<br>* Other names: Transjugular intrahepatic portosystemic shunt;Drug: Warfarin<br>* Oral warfarin was used for six months to one year prescribed at dosages to achieve an international normalized ratio (INR) of up to two times the upper limit of normal.<br>|
| Active Comparator: conservative treatment arm<br>Conservative treatment including endoscopic therapy，non-selective beta blockers (propranolol)and anticoagulation therapy (warfarin). | Drug: Propranolol<br>* Propranolol is a kind of non-selective beta blockers, and is used for reducing the portal pressure.<br>Procedure: Endoscopic therapy<br>* Endoscopic therapy includes the endoscopic variceal band ligation and sclerotherapy.<br>Drug: Warfarin<br>* Oral warfarin was used for six months to one year prescribed at dosages to achieve an international normalized ratio (INR) of up to two times the upper limit of normal.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variceal rebleeding | Variceal rebleeding rate in 3 years | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival time |  | 3 years | 
| Variceal rebleeding-related death rate |  | 3 years | 
| Treatment-related complications | Incidence of treatment-related complications | 3 years | 
| Transjugular intrahepatic portosystemic shunt success rate | Technical success rate of transjugular intrahepatic portosystemic shunt | 3 years |