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
概览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 270
- 试验地点
- 1
- 主要终点
- Incidence of Overt Hepatic Encephalopathy (OHE) within 3 Months After TIPS
概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Ursodeoxycholic Acid (UDCA) (Drug)
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.
干预措施: Lactulose (Drug)
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.
干预措施: Lactulose (Drug)
结局指标
主要结局
Incidence of Overt Hepatic Encephalopathy (OHE) within 3 Months After TIPS
时间窗: 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.
次要结局
未报告次要终点
研究者
Xiaoze Wang
Xiaoze Wang, MD
West China Hospital