Early TIPS Versus Glue Obliteration to Prevent Rebleeding From Gastric Varices

Study Overview
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Brief Summary
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The primary objective of the study is to demonstrate the superiority of an early tips strategy over standard treatment by glue obliteration (G0) in preventing bleeding recurrence or death at one year after a non GOV1 gastric variceal bleeding in cirrhotic patients initially treated by GO.

Official Title
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A Multicenter Randomized Clinical Trial Comparing Two Treatment Strategies to Prevent Rebleeding From Gastric Varices: Early TIPS Versus Glue Obliteration

Conditions
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Bleeding Gastric Varices, Cirrhosis

Intervention / Treatment
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* Procedure: Transjugular Portosytemic Shunt (TIPS)
* Procedure: glue obliteration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cirrhotic patients: the diagnosis of liver cirrhosis will be based on previous needle liver biopsy or on the combination of clinical, biochemical, and radiological findings. If biopsy findings are unavailable and in case of non-complicated cirrhosis, non-invasive markers will be used. Variceal bleeding at endoscopy from gastroesophageal gastric varices type 2 or isolated gastric varices type 1 or 2 (Sarin classification) according to the following criteria: endoscopic signs of an active spurting or oozing from gastric varices (GV); adherent blood clots, white nipple signs, or erosions on the GV and absence of other bleeding sources. Hemodynamically stable patient (Mean arterial pressure above 65 mmHg) without clinical significant rebleeding (Baveno criteria) within 12 hours after the initial endoscopy with glue obliteration. Written informed consent obtained. Exclusion Criteria: Pregnant woman or breastfeeding. Minor and patients older than 75 years. Non cirrhotic portal hypertension. Hepatocellular carcinoma outside the Milan criteria or other cancer at a palliative stage. Child Pugh score > 13. History of severe or refractory hepatic encephalopathy unrelated to gastrointestinal bleeding. Congestive heart failure. History or presence of pulmonary hypertension. Patients with other indication for TIPS. Uncontrolled gastric variceal bleeding. Portal vein cavernoma. Patient who have previously received a TIPS procedure. Failure to receive clear information in patients without an identified trusted person. Refusal of the participation agreement by signing the information form and consent as defined. Exclusion period from another biomedical study.

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 |
| --- | --- |
| Other: early TIPS<br>Transjugular portosytemic shunt within 72h | Procedure: Transjugular Portosytemic Shunt (TIPS)<br>* The TIPS is placed under radiologic guidance. A branch of the intrahepatic portal vein is punctured; afterwards, the splenic vein is catheterized so that a portal venography and pressure measurements can be performed. Then, the parenchymal track is dilated and a stent is placed. A final portography and pressure measurement in the main portal vein and the inferior caval vein are performed.<br>|
| Other: Glue obliteration<br>glue obliteration repeated sessions | Procedure: glue obliteration<br>* The standard protocol uses cyanoacrylate and lipiodol in 1:1 ratio injecting with no more than 1 mL at the varix each time. In most cases, cyanoacrylate is usually extruded into the stomach lumen within 1-3 months after injection. The French observational survey observed that a large majority (78%) of practitioners diluted glue with lipiodol and most (68%) proposed a proportion of glue to lipiodol of 1:1 the total volume injected per varix (from 1mL to 20 mL) varied substantially. Regarding the type of glue, although the majority of published data concern Histoacryl®, nearly half of practitioners used Glubran®. This lack of preference for one glue over the other may be explained by the fact that only Glubran® is approved in this indication in Europe.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of clinically significant rebleeding (upper gastrointestinal bleeding whatever its origin) | Defined by Baveno VI consens group as a recurrent melena or hematemesis resulting in any of the following: Hospital admission Blood transfusion 3 g/dL drop in hemoglobin | 12 months | 
| death |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality and liver-related mortality |  | Day 42 | 
| All-cause mortality and liver-related mortality |  | 12 months | 
| Incidence of rebleeding |  | Day 42 | 
| Incidence of rebleeding |  | Day 90 | 
| Incidence of rebleeding |  | 3 months | 
| Incidence of rebleeding |  | 12 months | 
| Cumulative number of packed red blood cells |  | Day 42 | 
| Cumulative number of packed red blood cells |  | 12 months | 
| Incidence of complications of cirrhosis (infections, ascites, hepatic encephalopathy, hepatorenal syndrome) during follow-up |  | 12 months | 
| Frequency of TIPS complications |  | 12 months | 
| Frequency of glue obliteration complications |  | 12 months | 
| MELD score (Model for End Stage Liver Disease) in TIPS group | MELD score = 9.57*LN(creatinin in mg/dl) + 3.78*LN(Bilirubin in mg/dl) + 11.2*LN(INR) + 6.43 | 6 months | 
| MELD score (Model for End Stage Liver Disease) in glue obliteration group | MELD score = 9.57*LN(creatinin in mg/dl) + 3.78*LN(Bilirubin in mg/dl) + 11.2*LN(INR) + 6.43 | 6 months | 
| Number of days of hospitalization |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bleeding gastric varices, cirrhosis, type 2 gastro-esophageal varices, isolated gastric varices, transjugular intra-hepatic porto systemic shunt (TIPS), portal hypertension, glue obliteration, tissue adhesive