UDCA to Prevent Post-TIPS Hepatic Encephalopathy (THEUDCA)

Sichuan University

Status: Not yet enrolling

Conditions: TIPS; Hepatic Encephalopathy (HE)

Treatments: Drug: Ursodeoxycholic Acid (UDCA); Drug: Lactulose

Study type: Interventional

Funder types: Other

Identifiers

NCT07273734

THE001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 270 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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270 participants in 2 patient groups

UDCA + Lactulose

Experimental group

Description:

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.

Treatment:

Drug: Lactulose

Drug: Ursodeoxycholic Acid (UDCA)

Lactulose Alone

Active Comparator group

Description:

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.

Treatment:

Drug: Lactulose