A Prospective, Multi-center, Randomized, Double-blind, Placebo-controlled Study: Fenofibrate Combined With Ursodeoxycholic Acid in Subjects With Primary Biliary Cholangitis and an Inadequate Response to Ursodeoxycholic Acid
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 150
- 试验地点
- 8
- 主要终点
- Percentage of patients with complete biochemical response
研究概览
简要总结
Current treatment guidelines recommend ursodeoxycholic acid (UDCA) as the first-line treatment for new-diagnosed primary biliary cholangitis (PBC) patients. However, up to 40% patients are insensitive to UDCA monotherapy, and evaluation of UDCA response at 12 months may result in long period of ineffective treatment. We aimed to develop a new criterion to reliably identify non-response patients much earlier. Recently, our team designed and validated a new early criterion for distinguishing high-risk PBC patients in a Chinese population for the first time. Our data indicated that PBC patients with ALP ≤ 2.5 × ULN, AST ≤ 2 × ULN, and TBIL ≤ 1 × ULN (Xi'an criterion) after 1 month UDCA treatment were likely to have better prognosis. It can be readily applied in the rapid identification of PBC patients who require additional therapeutic approaches. However, whether it is reasonable to apply it to the response definition of clinical research, and the guidance of PBC management and choice of second-line treatment, further research is needed.
详细描述
This is a multi-center, randomized, placebo-controlled, parallel-group study that will assess the efficacy and safety of fenofibrate in patients with PBC who had an inadequate biochemical response to UDCA, as defined by the Xi'an criteria. Fenofibrate or placebo 200 mg will be daily administered in combination with UDCA 13-15 mg/kg/d for 48 months. Patient safety will be monitored. Primary end-point will be the percentage of patients with a complete normalization of the ALP and TBIL. Secondary endpoints will include the percentage of drug-related adverse events, survival rates without liver transplantation or liver decompensation, time course of non-invasive liver fibrosis measurements (LSM), time course of endoscopic, ultrasound, and biochemical features of portal hypertension, time course of pruritus and of quality of life using validated scales.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must have provided written informed consent;
- •Age 18-75 years;
- •BMI 17-28 kg/m2
- •Male or female with a diagnosis of PBC, by at least two of the following criteria:
- •History of AP above ULN for at least six months;
- •Positive AMA titers (>1/40 on immunofluorescence or M2 positive by enzyme linked immunosorbent assay (ELISA) or positive PBC-specific antinuclear antibodies;
- •Documented liver biopsy result consistent with PBC.
- •Incomplete response to UDCA defined by Xi'an criteria (ALP >2.5× ULN, AST>2×ULN or TBIL>1×ULN) after UDCA treatment for 4-6 weeks with at least one abnormal test in ALP or TBIL.
排除标准
- •History or presence of other concomitant liver diseases.
- •ALT/AST > 5×ULN, TBIL > 3×ULN.
- •If female: known pregnancy, or has a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating.
- •Allergic to fenofibrate or ursodeoxycholic acid.
- •Taking hepatotoxic drugs (e.g., dapsone, erythromycin, fluconazole, ketoconazole, rifampicin) for more than 2 weeks within 6 months, and long-term hormonal users.
- •Recurrent variceal bleeding, poorly controlled hepatic encephalopathy or refractory ascites.
- •Patients with a history of severe cardiac, cerebrovascular, renal, respiratory disease or functional failure, and psychiatric disorders (including those due to alcohol and drug abuse).
- •Creatinine >1.5×ULN and creatinine clearance <60 ml/min.
- •Currently using statins (such as pravastatin, fluvastatin, and simvastatin), other fibrates (such as gemfibrozil and bezafibrate), and drugs structurally similar to fenofibrate (like ketoprofen).
- •Planned to receive an organ transplant or an organ transplant recipient.
- •Needing Liver transplantation within 1 year according to the Mayo Rick score.
- •Any other condition(s) that would compromise the safety of the subject or compromise the quality of the clinical study, as judged by the Investigator.
研究组 & 干预措施
Placebo
1 tablet/ day
干预措施: Placebo Combined With Ursodeoxycholic Acid (Drug)
Fenofibrate
200 mg/day
干预措施: Fenofibrate Combined With Ursodeoxycholic Acid (Drug)
结局指标
主要结局
Percentage of patients with complete biochemical response
时间窗: 48 weeks
The normalisation of Alkaline Phosphatase (ALP) and total bilirubin (TBIL).
次要结局
- Survival without transplantation and hepatic impairment(48 weeks)
- Percentage of patients having complete biochemical response(4, 12, 24, 36, and 48 weeks)
- Assessment of the fatigue and the quality of life(4, 12, 24, 36, and 48 weeks)
- Evolution of the biological markers of the hepatic function or being in the usual prognostic scores(48 weeks)
- Percentage of patients having biological or clinical adverse events(4, 12, 24, 36, and 48 weeks)
- Evolution of the biological markers of the hepatic function or being in the usual prognostic scores(4, 12, 24, 36, and 48 weeks)
研究者
Han Ying
Professor
Xijing Hospital of Digestive Diseases