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

A Multicenter Randomized Controlled Trial: Comparison of Underdilated Versus Standard Transjugular Intrahepatic Portosystemic Shunt in Preventing Rebleeding From Esophagogastric Varices in Patients With Cirrhosis

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.

Study Overview

• Status: Recruiting
• Conditions: Liver Cirrhosis; Gastroesophageal Varices Bleeding
• Intervention / Treatment: Procedure: Standard TIPS; Procedure: Underdilated TIPS

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.

• Study Type: Interventional
• Enrollment (Estimated): 170
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jun Tie, M.D.,Ph.D.; Phone Number: +862984771537; Email: tiejun7776@163.com

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Recruiting
      • Fourth Military Medical University
      • Contact: Jun Tie, M.D.,Ph.D.; Phone Number: +862984771537; Email: tiejun7776@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	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.
Experimental: 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.	Procedure: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of gastroesophageal variceal rebleeding.	Clinically significant rebleeding is defined in accordance with the Baveno V consensus criteria and is identified by recurrence of melena or hematemesis accompanied by any of the following: a) requirement for hospitalization; b) need for blood transfusion; c) hemoglobin decrease of ≥3 g/dL; or d) death within 6 weeks.	Throughout the entire follow-up period（up to 12 months）

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause rebleeding		Throughout the entire follow-up period（up to 12 months）
Stent dysfunction	Diagnosis of TIPS stent dysfunction follows a stepwise approach utilizing Doppler ultrasound, angiography, and measurement of the portosystemic pressure gradient (PPG). Stent dysfunction is diagnosed if either of the following criteria is met: (1) shunt stenosis ≥50% or complete occlusion; (2) an increase in PPG ≥25% compared to the baseline value measured immediately after stent placement. Angiography is indicated under the following circumstances: (1) recurrence of portal hypertension-related complications-TIPS stent dysfunction should be suspected upon recurrence of symptoms such as rebleeding, new-onset ascites, or persistence of ascites beyond 4-8 weeks; (2) color Doppler ultrasound findings-when flow direction is hepatofugal and mean maximum portal vein flow velocity (mVPmax) < 28 cm/s; when flow direction is hepatopetal and mVPmax < 39 cm/s.	12 months
New or worsening ascites	Defined as an increase of at least one grade in ascites severity on ultrasound (grading criteria: Grade 0 = none, Grade 1 = mild, Grade 2 = moderate, Grade 3 = large), or persistent ascites requiring paracentesis.	12 months
Incidence of overt hepatic encephalopathy	Hepatic encephalopathy is classified according to the 2022 European Association for the Study of the Liver (EASL) Clinical Practice Guidelines using the West-Haven criteria. Overt hepatic encephalopathy is defined as grade II or higher.	12 months
Liver function	Liver function will be evaluated using the Child-Pugh score (based on bilirubin, albumin, INR, ascites, and hepatic encephalopathy) and the Model for End-Stage Liver Disease (MELD) score.	12 months
Liver transplantation-free survival	Defined as the time from the TIPS procedure to the end of follow-up, liver transplantation, or death.	12 months

Collaborators and Investigators

• Sponsor: Air Force Military Medical University, China
• Investigators: Principal Investigator: Jun Tie, Air Force Military Medical University, China

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2025
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2028

Study Registration Dates

• First Submitted: September 30, 2025
• First Submitted That Met QC Criteria: November 19, 2025
• First Posted (Actual): November 28, 2025

Study Record Updates

• Last Update Posted (Actual): November 28, 2025
• Last Update Submitted That Met QC Criteria: November 19, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Liver Cirrhosis; Hepatic encephalopathy; Transjugular intrahepatic portosystemic shunt; Esophageal and gastric variceal bleeding
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Metabolic Diseases; Digestive System Diseases; Liver Diseases; Brain Diseases, Metabolic; Liver Failure; Hepatic Insufficiency; Fibrosis; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Liver Cirrhosis; Hepatic Encephalopathy
• Other Study ID Numbers: KY20252233-F-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No