Comparison of Underdilated Versus Standard TIPS in Preventing Variceal Rebleeding in Patients With Cirrhosis

NCT ID: NCT07253389

Last Updated: 2025-11-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 170 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-10-21
• Study Completion Date: 2028-03-31

Brief Summary

Transjugular intrahepatic portosystemic shunt (TIPS) is a key therapeutic intervention for complications of portal hypertension. However, the risk of post-procedural hepatic encephalopathy (HE) limits its broader clinical application. In the management of gastroesophageal variceal bleeding, the primary goal of TIPS is to reduce the portosystemic pressure gradient (PPG) to less than 12 mmHg (16 cmH₂O), which defines the standard TIPS procedure. The investigators hypothesize that, in patients undergoing TIPS for the prevention of variceal rebleeding, stent underdilation using a 6-mm balloon (underdilated TIPS) will not increase the risk of rebleeding but may reduce the incidence of overt HE and attenuate liver injury. To test this hypothesis, the investigators have designed a prospective, multicenter, randomized controlled trial.

Detailed Description

Transjugular intrahepatic portosystemic shunt (TIPS) is a pivotal intervention for managing complications of portal hypertension. However, its clinical utility is limited by the risk of post-procedural hepatic encephalopathy (HE).

The pathogenesis of post-TIPS HE involves two principal mechanisms: the diversion of portal venous blood flow away from the liver and a concurrent reduction in hepatic metabolic capacity. Following TIPS placement, portal venous blood is shunted directly into the systemic circulation, resulting in decreased functional hepatic perfusion. This hemodynamic alteration not only increases the risk of HE but may also exacerbate pre-existing hepatic dysfunction. Evidence suggests that stent diameter plays a critical role in determining shunt patency, efficacy of portal pressure reduction, and the incidence of HE. A stent that is too narrow may inadequately lower portal pressure, leading to suboptimal therapeutic outcomes and an increased risk of shunt stenosis. Conversely, an excessively large stent can substantially increase the risk of HE and further impair liver function. Therefore, identifying an optimal stent diameter that effectively reduces portal pressure while minimizing complications-particularly shunt-induced HE-remains a central focus in TIPS research, aiming to balance procedural efficacy with safety to improve patient outcomes.

Early studies demonstrated that the use of stents with larger diameters than conventional calibers for the portal and hepatic veins was associated with a disproportionately increased risk of hepatic encephalopathy (HE) without substantial additional benefit in portal pressure reduction. Consequently, a stent diameter of 10 mm became the standard during the era of bare metal stents. However, the introduction of polytetrafluoroethylene (PTFE)-covered stents has significantly reduced the incidence of shunt dysfunction and improved the durability of portal pressure reduction following transjugular intrahepatic portosystemic shunt (TIPS) placement. Clinical evidence indicates that 8 mm PTFE-covered stents can maintain long-term patency and achieve adequate portal decompression while substantially lowering the risk of HE. Despite these advancements, the overall incidence of post-TIPS HE remains high, approximately 30%. To further optimize clinical outcomes, recent studies have explored a "stent underdilation" strategy, involving dilation of an 8 mm PTFE-covered stent using a 6 mm balloon. Preliminary data suggest that this approach may further reduce the incidence of HE without significantly increasing the risk of recurrent portal hypertensive events. Nevertheless, there is currently a lack of prospective, head-to-head randomized controlled trials comparing the efficacy and safety of underdilated TIPS versus standard-diameter TIPS in the management of complications related to portal hypertension.

In the context of managing gastroesophageal variceal bleeding, the established therapeutic goal of TIPS is to reduce the portosystemic pressure gradient (PPG) to less than 12 mmHg (16 cmH₂O). Building upon this principle, the investigators propose the following hypothesis: in patients with esophagogastric variceal bleeding undergoing TIPS, underdilated TIPS will reduce the incidence of overt HE and attenuate liver function deterioration without increasing the risk of rebleeding. To evaluate this hypothesis, the investigators have designed the present prospective clinical trial.

Conditions

Liver Cirrhosis; Gastroesophageal Varices Bleeding

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Standard TIPS

Standard TIPS Group: In the standard group, the TIPS stent will be progressively dilated (starting at 8 mm of diameter) to the minimum diameter needed to achieve a portosystemic pressure gradient (PSPG) below 12 mm Hg.

Group Type: ACTIVE_COMPARATOR

Standard TIPS

Intervention Type: PROCEDURE

The procedure will be performed via a transjugular approach, with puncture conducted from the hepatic vein or inferior vena cava into the portal venous system. After successful cannulation, direct portography will be performed to visualize gastroesophageal varices and identify the optimal shunt tract, followed by targeted variceal embolization. A novel VIATORR® Controlled Expansion (VCX) stent graft (W. L. Gore \& Associates, Arizona, USA) will then be deployed intrahepatically to establish the transjugular intrahepatic portosystemic shunt (TIPS). Subsequently, the TIPS stent will be progressively dilated (starting at 8 mm of diameter) to the minimum diameter needed to achieve a portosystemic pressure gradient (PSPG) below 12 mm Hg.

Underdilated TIPS

Underdilated TIPS Group:In this group, the TIPS stent was underdilated using a 6-mm balloon, and the immediate post-procedure portal pressure gradient (PPG) was measured.

Group Type: EXPERIMENTAL

Underdilated TIPS

Intervention Type: PROCEDURE

The procedure will be performed via a transjugular approach, involving puncture from the hepatic vein or inferior vena cava into the portal venous system. Upon successful cannulation, direct portography will be performed to visualize varices and determine the optimal shunt tract, followed by targeted variceal embolization. A Novel VIATORR® Controlled Expansion (VCX) stent graft (W. L. Gore \& Associates, Arizona, USA) will then be deployed intrahepatically to establish the shunt. Subsequently, a 6-mm balloon will be used for suboptimal expansion of the TIPS stent, and the immediate portosystemic pressure gradient (PPG) will be measured.

Interventions

Underdilated TIPS

The procedure will be performed via a transjugular approach, involving puncture from the hepatic vein or inferior vena cava into the portal venous system. Upon successful cannulation, direct portography will be performed to visualize varices and determine the optimal shunt tract, followed by targeted variceal embolization. A Novel VIATORR® Controlled Expansion (VCX) stent graft (W. L. Gore \& Associates, Arizona, USA) will then be deployed intrahepatically to establish the shunt. Subsequently, a 6-mm balloon will be used for suboptimal expansion of the TIPS stent, and the immediate portosystemic pressure gradient (PPG) will be measured.

Intervention Type: PROCEDURE

Standard TIPS

The procedure will be performed via a transjugular approach, with puncture conducted from the hepatic vein or inferior vena cava into the portal venous system. After successful cannulation, direct portography will be performed to visualize gastroesophageal varices and identify the optimal shunt tract, followed by targeted variceal embolization. A novel VIATORR® Controlled Expansion (VCX) stent graft (W. L. Gore \& Associates, Arizona, USA) will then be deployed intrahepatically to establish the transjugular intrahepatic portosystemic shunt (TIPS). Subsequently, the TIPS stent will be progressively dilated (starting at 8 mm of diameter) to the minimum diameter needed to achieve a portosystemic pressure gradient (PSPG) below 12 mm Hg.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

1. Age 18-75 years;

2. Diagnosis of liver cirrhosis based on clinical and imaging findings according to the 2023 Consensus Opinion on the Clinical Diagnosis and Treatment of Liver Cirrhosis in China (Chinese Society of Gastroenterology); histological confirmation required if diagnosis is inconclusive;

3. High-risk acute variceal bleeding, defined as presence of any of the following: Child-Pugh class C; Child-Pugh class B with active endoscopic evidence of bleeding; early rebleeding within 5 days; or failure of pharmacologic and endoscopic therapy to control bleeding;

4. History of esophagogastric variceal bleeding with documented failure of standard first-line therapy (endoscopic intervention plus nonselective beta-blocker, NSBB);

5. Scheduled to undergo TIPS;

6. Hepatic and renal function meeting all of the following criteria: Child-Pugh score ≤13; AST and ALT <5× upper limit of normal (ULN); serum creatinine <1.5× ULN;

7. Ability and willingness to provide written informed consent.

Exclusion Criteria

(1) Budd-Chiari syndrome or other causes of non-cirrhotic portal hypertension; (2) current or prior malignancy, including hepatocellular carcinoma or extrahepatic malignancies; (3) complete thrombosis of the main portal vein; (4) severe psychiatric or neurological disorders (e.g., uncontrolled epilepsy, dementia); (5) history of liver resection or liver transplantation; (6) prior TIPS or surgical portosystemic shunt; (7) pregnancy or lactation; (8) any contraindication to TIPS, including severe right or left ventricular dysfunction, moderate-to-severe pulmonary hypertension despite optimal medical therapy, untreated severe valvular heart disease, or uncontrolled systemic infection; (9) acute variceal hemorrhage with MELD score ≥30 and/or arterial lactate >12 mmol/L, or presentation with acute-on-chronic liver failure (ACLF); (10) severe or refractory overt hepatic encephalopathy in the absence of a correctable spontaneous portosystemic shunt; (11) systemic conditions requiring ongoing systemic treatment with glucocorticoids or nonsteroidal anti-inflammatory drugs (NSAIDs).

• 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

Role: PRINCIPAL_INVESTIGATOR

Air Force Military Medical University, China

Locations

Fourth Military Medical University

Xi'an, Shaanxi, China

Site Status: RECRUITING

Countries

China

Central Contacts

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

Role: CONTACT

tiejun7776@163.com

+862984771537

Facility Contacts

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

Role: primary

tiejun7776@163.com

+862984771537

Other Identifiers

KY20252233-F-2

Identifier Type: -

Identifier Source: org_study_id