UDCA to Prevent Post-TIPS Hepatic Encephalopathy

NCT07273734 | Not Yet Recruiting

• 1 other identifier: THE001
• Study Type: interventional
• Target: 270
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hepatic Encephalopathy (HE); TIPS

Keywords

TIPS; UDCA; Hepatic Encephalopathy (HE); Ursodeoxycholic acid

Outcome Measures

Primary Outcomes (1)

• Incidence of Overt Hepatic Encephalopathy (OHE) within 3 Months After TIPS

  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).

Study Arms (2)

UDCA + Lactulose

EXPERIMENTAL

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); Drug: Lactulose

Lactulose Alone

ACTIVE COMPARATOR

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

Interventions

Lactulose DRUG

Syrup 25 mL BID, initiated after TIPS procedure, titrated to 1-2 soft stools/day, with dose reduction if diarrhea occurs.

Lactulose Alone; UDCA + Lactulose

Ursodeoxycholic Acid (UDCA) DRUG

13-15 mg/kg/day orally, in divided doses (BID), starting ≤72 hours before TIPS and continued for 3 months.

UDCA + Lactulose

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• West China Hospital: lead
• The Second Affiliated Hospital of Chongqing Medical University: collaborator
• First Affiliated Hospital of Kunming Medical University: collaborator
• Qianjiang Central Hospital of Chongqing: collaborator
• The Third People's Hospital of Kunming City: collaborator

Study Sites (1)

West China Hospital, Sichuan University

Chengdu, China

Location

Related Publications (11)

• Maharshi S, Sharma BC. Prophylaxis of hepatic encephalopathy: current and future drug targets. Hepatol Int. 2024 Aug;18(4):1096-1109. doi: 10.1007/s12072-024-10647-9. Epub 2024 Mar 16.

  PMID: 38492132 RESULT

• Kronsten VT, Paintsil EK, Rodrigues S, Seager MJ, Bernal W, Shawcross DL. Hepatic Encephalopathy: When Lactulose and Rifaximin Are Not Working. Gastroenterology. 2025 Jun;168(6):1076-1084.e1. doi: 10.1053/j.gastro.2025.01.010. Epub 2025 Jan 24. No abstract available.

  PMID: 39864468 RESULT

• Djernes L, Vilstrup H, Ott P, Eriksen PL. Blood ammonia concentration measurement - effects of sampling site and cirrhosis during induced hyperammonaemia. Metab Brain Dis. 2024 Nov 20;40(1):21. doi: 10.1007/s11011-024-01442-4.

  PMID: 39565434 RESULT

• Shawcross DL, Thabut D, Amodio P. Ammonia - an enduring foe - What evaluating whole body ammonia metabolism can teach us about cirrhosis and therapies treating hepatic encephalopathy. J Hepatol. 2023 Aug;79(2):266-268. doi: 10.1016/j.jhep.2023.04.039. Epub 2023 May 12. No abstract available.

  PMID: 37178732 RESULT

• Wang X, Luo X, Yang L. Achieving an effective pressure reduction after TIPS: The need for a new target. J Hepatol. 2021 Jul;75(1):246-248. doi: 10.1016/j.jhep.2021.02.010. Epub 2021 Feb 20. No abstract available.

  PMID: 33621635 RESULT

• Wang X, Liu G, Wu J, Xiao X, Yan Y, Guo Y, Yang J, Li X, He Y, Yang L, Luo X. Small-Diameter Transjugular Intrahepatic Portosystemic Shunt versus Endoscopic Variceal Ligation Plus Propranolol for Variceal Rebleeding in Advanced Cirrhosis. Radiology. 2023 Aug;308(2):e223201. doi: 10.1148/radiol.223201.

  PMID: 37606572 RESULT

• Xiang Y, Tie J, Wang G, Zhuge Y, Wu H, Zhu X, Xue H, Liu S, Yang L, Xu J, Zhang F, Zhang M, Wei B, Li P, Wang Z, Wu W, Chen C, Yang S, Han Y, Tang C, Qi X, Zhang C. Post-TIPS Overt Hepatic Encephalopathy Increases Long-Term but Not Short-Term Mortality in Cirrhotic Patients With Variceal Bleeding: A Large-Scale, Multicenter Real-World Study. Aliment Pharmacol Ther. 2025 Apr;61(7):1183-1196. doi: 10.1111/apt.18509. Epub 2025 Feb 17.

  PMID: 39962750 RESULT

• Liu J, Ma J, Yang C, Chen M, Shi Q, Zhou C, Huang S, Chen Y, Wang Y, Li T, Xiong B. Sarcopenia in Patients with Cirrhosis after Transjugular Intrahepatic Portosystemic Shunt Placement. Radiology. 2022 Jun;303(3):711-719. doi: 10.1148/radiol.211172. Epub 2022 Mar 15.

  PMID: 35289658 RESULT

• Lv Y, Wang Q, Luo B, Bai W, Li M, Li K, Wang Z, Xia D, Guo W, Li X, Yuan J, Zhang N, Wang X, Xie H, Pan Y, Nie Y, Yin Z, Fan D, Han G. Identifying the optimal measurement timing and hemodynamic targets of portal pressure gradient after TIPS in patients with cirrhosis and variceal bleeding. J Hepatol. 2025 Feb;82(2):245-257. doi: 10.1016/j.jhep.2024.08.007. Epub 2024 Aug 22.

  PMID: 39181214 RESULT

• Ehrenbauer AF, Egge JFM, Gabriel MM, Tiede A, Dirks M, Witt J, Wedemeyer H, Maasoumy B, Weissenborn K. Comparison of 6 tests for diagnosing minimal hepatic encephalopathy and predicting clinical outcome: A prospective, observational study. Hepatology. 2024 Aug 1;80(2):389-402. doi: 10.1097/HEP.0000000000000770. Epub 2024 Feb 13.

  PMID: 38349709 RESULT

• Casadaban LC, Parvinian A, Minocha J, Lakhoo J, Grant CW, Ray CE Jr, Knuttinen MG, Bui JT, Gaba RC. Clearing the Confusion over Hepatic Encephalopathy After TIPS Creation: Incidence, Prognostic Factors, and Clinical Outcomes. Dig Dis Sci. 2015 Apr;60(4):1059-66. doi: 10.1007/s10620-014-3391-0. Epub 2014 Oct 15.

  PMID: 25316553 RESULT

MeSH Terms

Conditions

Hepatic Encephalopathy

Interventions

Ursodeoxycholic Acid; Lactulose

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Deoxycholic Acid; Cholic Acids; Bile Acids and Salts; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholanes; Disaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Sugars

Central Study Contacts

Xiaoze Wang, MD

CONTACT

(+86)15208207573; wang_xiaoze@wchscu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Xiaoze Wang, MD

Study Record Dates

• First Submitted: November 26, 2025
• First Posted: December 9, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: December 9, 2025

Record last verified: 2025-11

Locations

CN (1)