Efficacy of Ursodeoxycholic Acid Versus Corticosteroids for the Treatment of Cholestatic Hepatitis Secondary to Immunotherapy: A Multicenter, Controlled, Randomized, Open Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 94
- 试验地点
- 12
- 主要终点
- Improvement of at least 25% in liver function tests on day 21 after randomization
研究概览
简要总结
The clinical trial aims to compare the effectiveness of ursodeoxycholic acid (UDCA) to corticosteroids in treating cholestatic hepatitis induced by immune checkpoint inhibitors (ICIs) over a 21-day period.
The trial presents a detailed scientific justification for comparing UDCA to corticosteroids, describing the treatment and detailing the follow-up procedures. It hypothesizes that UDCA could be superior to corticosteroids for treating ICI-related cholestatic hepatitis, based on its established use in primary biliary cholangitis and a favorable tolerance profile compared to corticosteroids.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults ≥18 years old
- •Any type of cancer except hepatocellular or cholangiocarcinoma
- •At least one ICI injection
- •Cholestatic hepatitis Grade CTC-AE 3 or 4
排除标准
- •Ongoing corticosteroids treatment
- •Other causes of hepatitis
- •Cirrhosis
- •ICI for hepatocellular carcinoma or cholangiocarcinoma
- •Biliary obstruction
- •Medical contraindication to corticosteroids or UDCA
- •Mixed or hepatocellular hepatitis
- •Total bilirubin > 1,5 ULN, Prothrombin rate < 70%
- •Medical contraindication to MRI or liver biopsy
- •Oher serious side effects requiring corticosteroids
- •Pregnant and breast-feeding patients
- •Patients under articles L1121-5 to 8 of the public health code
- •Lack of informed consent
- •Patients not affiliated with French social security system
- •Patients uncapable of understanding french
研究组 & 干预措施
Control arm
Patients randomized to the control arm will receive the reference treatment, corticosteroids. Corticosteroids will be given at a dose of 0.5-1 mg/kg/day for 21 days, followed by tapering in weekly steps of 10 mg until treatment discontinuation. At Day 21, in case of lack of treatment response, defined as no decrease of alkaline phosphatase and/or gamma-glutamyl transferase levels of at least 25% compared with baseline, corticosteroid tapering will continue, and ursodeoxycholic acid (UDCA) will be added at a dose of 13-15 mg/kg/day.
干预措施: Corticosteroids (Reference Treatment) (Drug)
Experimental arm
Patients randomized to the experimental arm will receive ursodeoxycholic acid (UDCA) as initial treatment for hepatitis. After evaluation of the primary endpoint at Day 21, UDCA treatment will be continued for a total duration of 6 months. In case of lack of response to UDCA, patients will continue UDCA and will additionally receive corticosteroids which represent the reference treatment.
干预措施: UDCA (Ursodeoxycholic acid) (Drug)
结局指标
主要结局
Improvement of at least 25% in liver function tests on day 21 after randomization
时间窗: 21 days after randomization
The rate of patients showing an improvement of at least 25% in liver function tests (alkaline phosphatase and/or gamma-GT) on Day 21 after randomization.
次要结局
- Rate of Hepatitis Resolution at 6 Months(6 Months after randomization)
- Time to Hepatitis Resolution(From Randomization to end of follow-up at 12 months)
- Tolerance to UDCA and/or Corticosteroids(From treatment initiation following the randomization to end of follow-up at 12 months)
- Resumption of immunotherapy(Within 12 months after randomization)