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Interventional Devascularization Plus HVPG-Guided Carvedilol Therapy vs TIPS

Not Applicable
Conditions
Gastric Varices Bleeding
Liver Cirrhoses
Interventions
Procedure: interventional devascularization
Procedure: TIPS
Registration Number
NCT04198259
Lead Sponsor
Air Force Military Medical University, China
Brief Summary

Gastric varices (GV) are present in around 20% of patients with cirrhosis. Bleeding from GV accounts for 10-20% of all variceal bleeding. For the prevention of gastric variceal bleeding, TIPS or BRTO as firstline treatments were suggested.

No randomized trials have compared BRTO with other therapies. BRTO and its variations might increase portal pressure and might worsen complications, such as ascites or bleeding from EV. In this regard, if NSBB is combined with BRTO and its variations (we called interventional devascularization) for those HVPG responders, the drawbacks of interventional devascularization might be overcome. Therefore, the investigators conducted this RCT to compare the effectiveness and safety of TIPS with those of interventional devascularization in the prevention of rebleeding from gastric varices.

Detailed Description

Gastric varices (GV) are present in around 20% of patients with cirrhosis. Bleeding from GV accounts for 10-20% of all variceal bleeding. GV are classified according to their location in the stomach and their relationship with esophageal varices (EV). Accordingly, GV are divided into gastroesophageal varices (GOV) and isolated gastric varices (IGV) . The management of type 1 GOV, which extend from the esophagus along the lesser curvature of the stomach, is similar to the management of EV. Historically, bleeding from type 2 GOV (i.e. GOV extending into the fundus), type 1 IGV (i.e. located in the fundus) and type 2 IGV (i.e. located anywhere in the stomach), is considered to be more severe and difficult to treat than EV bleeding. Few studies, mostly retrospective and uncontrolled, have focused on the management of non-GOV1 GV, and the optimal treatment remains controversial.

For the prevention of gastric variceal bleeding, treatment principles can be classified into two categories: decreasing portal pressure and obstructing GEV. Methods for decreasing portal pressure include medications (NSBB), radiological intervention (TIPS) and surgery. In contrast, methods for treating the obstruction of GEV include endoscopic approaches (EVL, EIS) or radiological intervention (such as BRTO). Recent portal hypertensive bleeding suggested TIPS or BRTO as firstline treatments in the prevention of rebleeding.

BRTO is a procedure for treatment of fundal varices associated with a large gastro-/splenorenal collateral. The technique involves retrograde cannulation of the left renal vein by the jugular or femoral vein, followed by balloon occlusion and slow infusion of sclerosant to obliterate the gastro-/splenorenal collateral and fundal varices. Several variations of the technique exist, such as balloon-occluded antegrade transvenous obliteration or occlusion of the collateral by the placement of a vascular plug or coils. BRTO has the theoretical advantage over TIPS that it does not divert portal blood inflow from the liver. On the other hand, BRTO and its variations might increase portal pressure and might worsen complications, such as ascites or bleeding from EV. In this regard, if NSBB is combined with BRTO and its variations (we called interventional devascularization) for those HVPG responders, the drawbacks of interventional devascularization might be overcome.

Therefore, the investigators conducted this RCT to compare the effectiveness and safety of TIPS with those of interventional devascularization in the prevention of rebleeding from gastric varices.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
212
Inclusion Criteria
  • Liver cirrhosis diagnosed by clinical examination, imaging or biopsy
  • Patients with a previous history of variceal hemorrhage
  • Gastric variceal confirmed by an endoscopic examination, including IGV1 or IGV2
  • Aged 18 to 75 years
  • Adequate liver and kidney function, including Child-Turcotte-Pugh score < 12, MELD score <19, and serum creatinine less than 2 times the upper limit of normal.
Exclusion Criteria
  • Active variceal bleeding
  • Esophageal variceal, including GOV1 or GOV2 type, mainly esophageal varices;
  • Refractory ascites
  • Patients with contraindication to treatment of TIPS, including congestive heart failure, NYHA III and IV, pulmonary arterial hypertension(>50mmHg), polycystic liver, intrahepatic duct dilatation, spontaneous bacterial peritonitis, hepatic encephalopathy
  • Patients with contraindication to treatment of Carvedilol, including asthma, insulin-dependent diabetes, peripheral vascular diseases
  • Child-Turcotte-Pugh score >=12, or MELD score >=19
  • Budd-Chiari syndrome
  • The main portal vein thrombosis is greater than 50%
  • Malignancies
  • An uncontrolled infection
  • Previously treated with TIPS, splenectomy pericardia vascular disconnection, or surgical shunts
  • HIV or HIV related illness
  • Allergic to contrast agent
  • Lactating or pregnant
  • Non-compliant patients

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
interventional devascularizationinterventional devascularizationInterventional devascularization includes BRTO and similar procedure. Several variations of the technique exist, such as balloon-occluded antegrade transvenous obliteration or occlusion of the collateral by the placement of a vascular plug or coils.
Transjugular intrahepatic portosystemic shuntTIPSTIPS is an artificial channel within the liver that establishes communication between the inflow portal vein and the outflow hepatic vein.
Primary Outcome Measures
NameTimeMethod
Cumulative incidence of gastric variceal rebleeding12 months

Confirmed by endoscopy

Secondary Outcome Measures
NameTimeMethod
Cumulative incidence of variceal hemorrhage related death12 months
Cumulative incidence of hepatic encephalopathy (HE)12 months

HE is classified as covert HE and overt HE

Cumulative incidence of death12 months

all cause mortality

Cumulative incidence of adverse events12 months

number of adverse events and adverse reactions in each arm

Correlation between hepatic venous pressure gradient response and cardiac index response to Carvedilol12 months

Investigate non-invasive tools for risk stratification

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