UDCA to Prevent Post-TIPS Hepatic Encephalopathy (THEUDCA)

November 26, 2025 updated by: Xiaoze Wang, West China Hospital

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Ursodeoxycholic Acid Plus Lactulose vs Lactulose Alone for the Prevention of Overt Hepatic Encephalopathy After TIPS Placement

Hepatic encephalopathy (HE) commonly occurs after transjugular intrahepatic portosystemic shunt (TIPS). Ursodeoxycholic acid (UDCA) has been reported to alleviate neurodegenerative disease recently. This open-label multicenter randomized controlled trial tests whether adding UDCA (13-15 mg/kg/day) to standard lactulose prophylaxis reduces the incidence of overt HE (OHE; West Haven grade II-IV) after TIPS, compared with lactulose alone. The regimen starts within 72 hours before TIPS and continues for 3 months. The trial aims to evaluate the effect of UDCA in reducing the incidence of post-TIPS OHE.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Post-TIPS OHE occurs in 35-50% of patients and worsens quality of life and resource use. Existing guidance consistently recommends lactulose as the backbone therapy for HE and for secondary prophylaxis, titrated to 2-3 soft stools/day; however, evidence for primary prophylaxis after TIPS has been limited and heterogeneous, and consensus varies across documents. Hydrophilic bile acids, especially ursodeoxycholic acid (UDCA), have demonstrated important anti-apoptotic and neuroprotective activities in clinical practice. Published experimental and clinical evidence suggests its potential therapeutic use as a disease-modifier in neurodegenerative and metabolic brain diseases. This trial evaluates whether bile-acid modulation with UDCA at standard hepatology dosing (13-15 mg/kg/day) combined with lactulose reduces early post-TIPS OHE. The protocol uses stratified randomization, prespecified outcome adjudication (West Haven), and intention-to-treat analysis. Key secondary endpoints include mortality, transplant-free survival, minimal HE tests (PHES, Stroop test), frailty, quality of life, and bile-acid/metabolomic profiling in optional sub-studies.

Study Type

Interventional

Enrollment (Estimated)

270

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Chengdu, China
        • West China Hospital, Sichuan University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age 18-80 years.
  • Confirmed cirrhosis (biopsy, elastography, or standard radiologic/biochemical criteria).
  • Elective TIPS for (a) refractory/recurrent ascites and/or (b) recurrent variceal bleeding not responsive to treatment with endoscopic band ligation and beta-blockers.
  • Preemptive TIPS for patients with variceal bleeding and Child-Pugh C (10-13 points), patients with Child-Pugh B and active bleeding during endoscopy, or patients with hepatic venous pressure gradient (HVPG) ≥ 20 mmHg.
  • Ability to start study drug within 72 hours before TIPS.
  • Signed informed consent.

Exclusion Criteria:

  • Contraindications to TIPS (e.g., severe heart failure ≥NYHA III, severe pulmonary hypertension, uncontrolled sepsis, advanced HCC at risk with TIPS, unrelieved biliary obstruction, Child-Pugh score >13, main-trunk PVT if not recanalizable, technical infeasibility).
  • Prior OHE grade II-IV without precipitating factor; overt neurological disease affecting cognition (e.g., Parkinson's, Alzheimer's).
  • Current or planned ursodeoxycholic acid (UDCA) therapy for an approved indication (e.g., primary biliary cholangitis), or UDCA use within the prior 3 months.
  • Current/recent rifaximin use (<3 months) or strong UDCA contraindication/hypersensitivity.
  • Salvage TIPS.
  • Non-cirrhotic portal hypertension.
  • Pregnancy/lactation.
  • Any condition that, in investigators' judgment, precludes safe participation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: UDCA + Lactulose
Ursodeoxycholic acid (UDCA) 13-15 mg/kg/day orally, in divided doses (BID), starting ≤72 hours before TIPS and continued for 3 months. Lactulose syrup (25 mL BID) is initiated after TIPS procedure, titrated to achieve 1-2 soft stools per day, with stepwise dose reduction if diarrhea occurs.
Drug: Ursodeoxycholic Acid (UDCA)
13-15 mg/kg/day orally, in divided doses (BID), starting ≤72 hours before TIPS and continued for 3 months.
Drug: Lactulose
Syrup 25 mL BID, initiated after TIPS procedure, titrated to 1-2 soft stools/day, with dose reduction if diarrhea occurs.
Active Comparator: Lactulose Alone
Lactulose syrup (25 mL BID) is initiated after TIPS procedure, titrated to achieve 1-2 soft stools per day, with dose reduction as needed if diarrhea develops.
Drug: Lactulose
Syrup 25 mL BID, initiated after TIPS procedure, titrated to 1-2 soft stools/day, with dose reduction if diarrhea occurs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Overt Hepatic Encephalopathy (OHE) within 3 Months After TIPS
Time Frame: From TIPS procedure (Day 0) to 3 months post-TIPS (Day 90).
OHE defined as first occurrence of West Haven grade II-IV hepatic encephalopathy within 3 months after covered TIPS, adjudicated by investigator assessment according to West Haven criteria.
From TIPS procedure (Day 0) to 3 months post-TIPS (Day 90).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

West China Hospital

Collaborators

The Second Affiliated Hospital of Chongqing Medical University
Qianjiang Central Hospital of Chongqing
The Third People's Hospital of Kunming City
First Affiliated Hospital of Kunming Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 1, 2026

Primary Completion (Estimated)

June 30, 2027

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

November 26, 2025

First Submitted That Met QC Criteria

November 26, 2025

First Posted (Estimated)

December 9, 2025

Study Record Updates

Last Update Posted (Estimated)

December 9, 2025

Last Update Submitted That Met QC Criteria

November 26, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • THE001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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