TIPS in Fundal Variceal Bleeding (the TFB Study)

Study Overview
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Brief Summary
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In the last years, important advances have been done in the treatment and prevention of fundal variceal bleeding in patients with cirrhosis. Experts agree that the combination of pharmacological and endoscopic therapy (with tissue adhesives) should be the first line therapy in the acute bleeding episode from isolated gastric varices (IGV1) or type 2 gastroesophageal varices (GOV2) varices; whereas transjugular intrahepatic portosystemic shunt (TIPS) is considered a rescue therapy. TIPS has been shown to effectively prevent variceal rebleeding but with a potential increase in the incidence of hepatic encephalopathy and/or liver failure. In this sense, a recent randomized controlled trial (RCT) in esophageal variceal bleeding showed that an early TIPS, performed during the first 72h after patient admission resulted in a significant decrease in failure to control bleeding and early and late rebleeding. Moreover, survival was also significantly increased as well as other portal-hypertension related complications (ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, etc). The present study is directed at comparing the outcome of patients with acute bleeding from fundal varices (IGV1 or GOV2) treated by standard therapy (vasoactive drugs + endoscopic injection of tissue adhesives) with or without early TIPS (performed during the first 1-5 days after admission). Main end-point will be survival free of variceal rebleeding at 1 year from inclusion.

Official Title
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Efficacy of Early-TIPS in the Treatment of Acute Variceal Bleeding From Gastric Fundal Varices: a RCT vs Standard Therapy

Conditions
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Portal Hypertension, Bleeding Gastric Varices

Intervention / Treatment
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* Device: Early TIPS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients developing acute variceal bleeding from GOV2 and/or IGV1 defined according to Baveno II criteria, admitted in the Hospital and receiving standard combined medical therapy (somatostatin 3 mg/12h continuous IV infusion or terlipressin, 2mg/4h IV + endoscopic injection of tissue adhesives as per center protocol). Exclusion Criteria: Hepatocarcinoma without therapeutic options (according to Milan criteria). Portal or mesenteric vein thrombosis avoiding the performance of TIPS. Acute alcoholic hepatitis. Platelet count < 20.000/mm3. Previous treatment with portosystemic shunt. Pregnancy. Previous inclusion in the current study. Terminal liver disease (bilirrubin > 10 mg/dL and/or prothrombin index < 30%); or other fatal non-liver diseases. Denied informed consent.

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: Early TIPS<br>Standard treatment to achieve initial hemostasis: vasoactive drugs (somatostatin or terlipressin) + endoscopic injection of tissue adhesives according to the center protocol. Performance of TIPS in the first 5 days following acute gastric variceal bleeding. | Device: Early TIPS<br>* TIPS (first 5 days)<br>|
| Placebo Comparator: Control<br>Standard treatment to achieve initial hemostasis: vasoactive drugs (somatostatin or terlipressin) + endoscopic injection of tissue adhesives according to the center protocol. Standard combined endoscopic and pharmacological therapy as a secondary prophylaxis (beta-blockers or carvedilol + repeated injection of tissue adhesives until the erradication of the fundal varices). | Device: Early TIPS<br>* TIPS (first 5 days)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined: Absence of rebleeding + survival | The primary endpoint combines absence of rebleeding + survival during the first 1 year after inclusion in the study. Patients to compare are those with liver cirrhosis and acute bleeding from IGV1 or GOV2 varices initially treated with combined pharmacological and endoscopic therapy. Those patients will be randomized to receive a TIPS or standard medical therapy (pharmacological + endoscopic injection of tissue adhesives) | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absence of portal hypertension-related complications (ascites, spontaneous bacterial peritonitis, hepatorenal syndrome) | Comparison of the development of portal-hypertension related complications. | 6 weeks and 1 year | 
| Transfusional requirements | We will compare the number of packed red blood cells required by each treatment arms as a surrogate of rebleeding. | 6 weeks and 1 year | 
| Individual adverse events | Related and not related to the therapies under study. | 1 year | 
| Hospital stay | Including the stay for the index bleed and also readmissions due to complications of liver disease. | 1 year | 
| Use of hospital resources | Use of hospital resources other than specified in the treatment arms (TIPS, revision of TIPS patency, derivative surgery or additional endoscopic therapy). | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bleeding gastric varices, Transjugular intrahepatic portosystemic shunt (TIPS), Injection of adhesives