Interventional Devascularization Plus HVPG-Guided Carvedilol Therapy vs TIPS

NCT ID: NCT04198259

Last Updated: 2020-02-05

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 212 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-01
• Study Completion Date: 2022-12-31

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.

Conditions

Gastric Varices Bleeding; Liver Cirrhoses

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

interventional devascularization

Interventional 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.

Group Type: ACTIVE_COMPARATOR

interventional devascularization

Intervention Type: PROCEDURE

Interventional devascularization (BRTO and its variations) is a procedure for treatment of fundal varices associated with a large gastro-/splenorenal collateral.

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.

Group Type: EXPERIMENTAL

TIPS

Intervention Type: PROCEDURE

TIPS is very effective in the treatment of bleeding GV, with more than a 90% success rate for initial hemostasis. It frequently requires additional embolization of spontaneous collaterals feeding the varices. The incidence of encephalopathy was higher after TIPS.

Interventions

interventional devascularization

Interventional devascularization (BRTO and its variations) is a procedure for treatment of fundal varices associated with a large gastro-/splenorenal collateral.

Intervention Type: PROCEDURE

TIPS

TIPS is very effective in the treatment of bleeding GV, with more than a 90% success rate for initial hemostasis. It frequently requires additional embolization of spontaneous collaterals feeding the varices. The incidence of encephalopathy was higher after TIPS.

Intervention Type: PROCEDURE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Air Force Military Medical University, China

OTHER

Sponsor Role: lead

Responsible Party

Tie Jun

Director of clinical research

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jun Tie, M.D.,Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Air Force Military Medical University, China

Central Contacts

Jun Tie, M.D.,Ph.D.

Role: CONTACT

tiejun7776@163.com

+862984771537

Hui Chen, M.D.,Ph.D.

Role: CONTACT

qychenhui@163.com

+862984771537

Other Identifiers

KY20192116-F-1

Identifier Type: -

Identifier Source: org_study_id