Interventional Devascularization Plus HVPG‐Guided Carvedilol Therapy vs TIPS

Liver Cirrhoses Clinical Trial

Official title:

Interventional Devascularization Plus HVPG‐Guided Carvedilol Therapy vs TIPS for the Prevention of Gastric Variceal Rebleeding in Patients With Liver Cirrhosis: A Prospective, Randomized, Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04198259
• Other study ID #: KY20192116-F-1
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 1, 2020
• Est. completion date: December 31, 2022

Study information

• Verified date: February 2020
• Source: Fourth Military Medical University
• Contact: Jun Tie, M.D.,Ph.D.
• Phone: +862984771537
• Email: tiejun7776[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 212
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Esophageal and Gastric Varices
• Fibrosis
• Gastric Varices Bleeding
• Liver Cirrhoses
• Liver Cirrhosis

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Fourth Military Medical University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cumulative incidence of gastric variceal rebleeding	Confirmed by endoscopy	12 months
Secondary	Cumulative incidence of variceal hemorrhage related death		12 months
Secondary	Cumulative incidence of hepatic encephalopathy (HE)	HE is classified as covert HE and overt HE	12 months
Secondary	Cumulative incidence of death	all cause mortality	12 months
Secondary	Cumulative incidence of adverse events	number of adverse events and adverse reactions in each arm	12 months
Secondary	Correlation between hepatic venous pressure gradient response and cardiac index response to Carvedilol	Investigate non-invasive tools for risk stratification	12 months