Comparing UDCA and Corticosteroids in Immunotherapy Induced Cholestatic Hepatitis

Официальное название

Efficacy of Ursodeoxycholic Acid Versus Corticosteroids for the Treatment of Cholestatic Hepatitis Secondary to Immunotherapy: A Multicenter, Controlled, Randomized, Open Trial

Обзор

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.

Вмешательства

• Препарат UDCA (Ursodeoxycholic acid)
  Ursodeoxycholic acid (UDCA) will be administered orally at an initial dose of 13-15 mg/kg/day, divided into two daily doses. After assessment of the primary endpoint at Day 21, UDCA will be continued for a total treatment duration of 6 months. In case of absence of treatment response, defined as no decrease of alkaline phosphatase and/or gamma-glutamyl transferase levels of at least 25% compared with baseline, corticosteroids which represent the reference treatment, will be added at a dose of 0.
• Препарат Corticosteroids (Reference Treatment)
  Corticosteroids will be administered orally at a dose of 0.5-1 mg/kg/day for 21 days, followed by a tapering schedule of 10 mg per week until treatment discontinuation. At Day 21, if there is no adequate response (defined as less than 25% decrease in alkaline phosphatase and/or gamma-glutamyl transferase from baseline), the corticosteroid taper will continue and ursodeoxycholic acid (UDCA) will be added at a dose of 13-15 mg/kg/day.

Первичные конечные точки

• Improvement of at least 25% in liver function tests on day 21 after randomization [Срок оценки: 21 days after randomization]

Вторичные конечные точки (4)

• Rate of Hepatitis Resolution at 6 Months [Срок оценки: 6 Months after randomization]
• Time to Hepatitis Resolution [Срок оценки: From Randomization to end of follow-up at 12 months]
• Tolerance to UDCA and/or Corticosteroids [Срок оценки: From treatment initiation following the randomization to end of follow-up at 12 months]
• Resumption of immunotherapy [Срок оценки: Within 12 months after randomization]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Франция · 6 центров

• CHU Bordeaux — Bordeaux
• HCL Croix Rousse — Lyon
• CHU Montpellier — Montpellier
• APHP Paul Brousse — Paris
• CHU Poitiers — Poitiers
• CHU Toulouse — Toulouse

Идентификаторы

NCT: NCT07378761 · RECHMPL24_0328 · 2025-521317-50-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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