Underdilated VCX-TIPS Versus EVL Plus NSBB for Secondary Prophylaxis of Variceal Bleeding in Cirrhosis

NCT07587671 | Not Yet Recruiting DMC

• 1 other identifier: THE002
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 3

Brief Summary

Variceal bleeding is a major complication of portal hypertension in patients with cirrhosis and is associated with substantial risks of rebleeding and death. Current guidelines recommend endoscopic variceal ligation combined with nonselective beta-blockers as standard secondary prophylaxis for esophageal variceal bleeding and type 1 gastroesophageal variceal bleeding. Transjugular intrahepatic portosystemic shunt can markedly reduce portal pressure and prevent recurrent variceal bleeding, but its broader use in secondary prophylaxis is limited by the risk of post-TIPS hepatic encephalopathy and liver function deterioration. The VIATORR Controlled Expansion stent is designed to allow controlled expansion between 8 and 10 mm. However, even 8-mm TIPS may still be associated with a substantial risk of overt hepatic encephalopathy. This trial evaluates an underdilated VCX-TIPS strategy, in which a commercially available 8-10 mm VIATORR Controlled Expansion stent is initially dilated only with a 6-mm balloon, aiming to achieve sufficient portal decompression while reducing the risk of excessive shunting. This is a prospective, multicenter, open-label, parallel-group, randomized superiority trial. Eligible patients with cirrhosis who have recovered from acute esophageal variceal bleeding or type 1 gastroesophageal variceal bleeding and have entered the secondary prophylaxis phase will be randomly assigned in a 1:1 ratio to receive either underdilated VCX-TIPS or endoscopic variceal ligation plus nonselective beta-blockers. The primary outcome is the composite of all-cause death or clinically significant upper gastrointestinal rebleeding within 1 year after randomization.

Conditions

Liver Cirrhosis; Portal Hypertension; Gastroesophageal Varices Bleeding; Esophageal Varices; Hepatic Encephalopathy

Keywords

Cirrhosis; Portal hypertension; Esophageal variceal bleeding; Secondary prophylaxis; Transjugular intrahepatic portosystemic shunt; Underdilation; Endoscopic variceal ligation; Hepatic encephalopathy

Outcome Measures

Primary Outcomes (1)

• Composite of All-Cause Death or Clinically Significant Upper Gastrointestinal Rebleeding

  Time from randomization to the first occurrence of all-cause death or clinically significant upper gastrointestinal rebleeding. Clinically significant upper gastrointestinal rebleeding is defined as hematemesis, melena, fresh blood from a nasogastric tube, or endoscopically documented bleeding resulting in hospitalization, blood transfusion, a decrease in hemoglobin of at least 30 g/L, hemodynamic instability, urgent endoscopic, interventional radiologic, or surgical hemostatic therapy, or bleeding-related death. The rebleeding event does not have to be confirmed as variceal in origin for the primary endpoint.

  From randomization to 1 year

Secondary Outcomes (9)

• Transplant-Free Survival

  From randomization to 12 and 24 months

• Liver-Related Mortality

  From randomization to 12 and 24 months

• Clinically Significant Upper Gastrointestinal Rebleeding

  From randomization to 42 days, 90 days, 180 days, 365 days, and 24 months

• Variceal-Related Rebleeding

  From randomization to 42 days, 90 days, 180 days, 365 days, and 24 months

• Overt Hepatic Encephalopathy

  From randomization to 12 and 24 months

Study Arms (2)

Underdilated VCX-TIPS

EXPERIMENTAL

Participants assigned to this group will undergo transjugular intrahepatic portosystemic shunt creation using a commercially available 8-10 mm VIATORR Controlled Expansion stent. After stent deployment, the stent will be initially dilated only with a 6-mm balloon to achieve an initial effective shunt diameter of approximately 6 mm. Further dilation to 8 mm will be allowed only under predefined rescue conditions. Selective embolization of responsible variceal inflow vessels may be performed according to standardized procedures.

Procedure: Underdilated VCX-TIPS

EVL Plus NSBB

ACTIVE COMPARATOR

Participants assigned to this group will receive standard secondary prophylaxis using serial endoscopic variceal ligation combined with nonselective beta-blockers. EVL will be repeated approximately every 4 weeks until variceal eradication or conversion to a low-risk status. Carvedilol will be preferred, with propranolol as an alternative if carvedilol is not tolerated or is clinically inappropriate.

Procedure: Endoscopic Variceal Ligation; Drug: Nonselective Beta-Blockers

Interventions

Underdilated VCX-TIPS PROCEDURE

Transjugular intrahepatic portosystemic shunt will be created using a VIATORR Controlled Expansion 8-10 mm stent. The stent will initially be dilated only with a 6-mm balloon. Portal pressure gradient will be measured before and after shunt creation. Additional embolization of responsible variceal inflow vessels may be performed if clinically indicated. Further dilation to 8 mm will be reserved for predefined rescue situations.

Underdilated VCX-TIPS

Endoscopic Variceal Ligation PROCEDURE

Serial endoscopic variceal ligation will be performed according to standardized endoscopic procedures. EVL will be repeated approximately every 4 weeks until variceal eradication or conversion to a low-risk status. For type 1 gastroesophageal varices with substantial gastric extension or high-risk bleeding stigmata, endoscopic tissue adhesive injection may be performed according to local standardized procedures.

EVL Plus NSBB

Nonselective Beta-Blockers DRUG

Carvedilol will be the preferred nonselective beta-blocker, starting at 6.25 mg once daily and increasing to 12.5 mg once daily after 1 week if tolerated. Dose adjustment, temporary discontinuation, or switching to propranolol will be allowed according to heart rate, blood pressure, renal function, infection status, and overall tolerability.

EVL Plus NSBB

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 75 years, regardless of sex.
• Diagnosis of liver cirrhosis based on previous histology, imaging, laboratory tests, and/or clinical manifestations.
• Hospitalization for acute upper gastrointestinal bleeding, with endoscopic confirmation that the bleeding is related to esophageal varices or type 1 gastroesophageal varices.
• Successful control of acute bleeding after standard acute-phase treatment, with stable vital signs and entry into the secondary prophylaxis phase.
• Child-Pugh score of 5 to 13.
• The investigator judges that both underdilated VCX-TIPS and EVL plus NSBB are clinically feasible and that randomization is appropriate.
• The participant or legally authorized representative understands the study procedures and voluntarily signs written informed consent.

You may not qualify if:

• Hemodynamic instability, persistent active bleeding, or need for immediate rescue TIPS, surgical hemostasis, or interventional radiologic hemostasis.
• A strong current indication for early or pre-emptive TIPS that makes randomization to EVL plus NSBB clinically inappropriate.
• Child-Pugh score greater than 13.
• Previous TIPS, surgical portosystemic shunt, BRTO, CARTO, PARTO, or other procedures that substantially alter portosystemic blood flow.
• Isolated gastric varices, type 2 gastroesophageal varices, ectopic varices, or a bleeding source other than esophageal varices or type 1 gastroesophageal varices.
• Non-cirrhotic portal hypertension.
• Cavernous transformation of the portal vein or portal venous thrombosis that makes standardized TIPS technically infeasible.
• Previous recurrent or refractory overt hepatic encephalopathy, or a history of West Haven grade II to IV overt hepatic encephalopathy unrelated to gastrointestinal bleeding.
• Severe heart failure, severe pulmonary hypertension, severe tricuspid regurgitation, right heart failure, or other contraindications to TIPS.
• Uncontrolled severe infection, sepsis, or multiple organ failure.
• Hepatocellular carcinoma beyond the Milan criteria or other advanced malignancy.
• Severe renal insufficiency requiring long-term renal replacement therapy.
• Pregnancy or breastfeeding.
• Absolute contraindication to EVL, NSBB, or TIPS.
• Any condition that, in the investigator's judgment, makes the participant unsuitable for the study or unable to complete follow-up.

Sponsors & Collaborators

• West China Hospital: lead
• West China Xiamen Hospital: collaborator
• West China Tianfu Hospital: collaborator
• Southwest Hospital, China: collaborator
• The Second Affiliated Hospital of Chongqing Medical University: collaborator
• The Second Affiliated Hospital of Kunming Medical University: collaborator
• Chongqing Qianjiang Central Hospital: collaborator
• Chengdu Shangjin Nanfu Hospital: collaborator

Study Sites (3)

West China Hospital, Sichuan University

Chengdu, 610041, China

Location

The Second Affiliated Hospital of Chongqing Medical University

Chongqing, 610041, China

Location

West China Xiamen Hospital, Sichuan University

Xiamen, 610041, China

Location

MeSH Terms

Conditions

Liver Cirrhosis; Hypertension, Portal; Esophageal and Gastric Varices; Hepatic Encephalopathy; Fibrosis

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Esophageal Diseases; Gastrointestinal Diseases; Liver Failure; Hepatic Insufficiency; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Xiaoze Wang, MD

CONTACT

(+86)15208207573; wang_xiaoze@wchscu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 7, 2026
• First Posted: May 14, 2026
• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): March 31, 2029
• Study Completion (Estimated): July 30, 2030
• Last Updated: May 14, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)