Comparing UDCA and Corticosteroids in Immunotherapy Induced Cholestatic Hepatitis (CHILURSO)

University Hospital Center (CHU)

Status and phase: Not yet enrolling; Phase 2

Conditions: Immune-Mediated Cholestasis

Treatments: Drug: UDCA (Ursodeoxycholic acid); Drug: Corticosteroids (Reference Treatment)

Study type: Interventional

Funder types: Other

Identifiers

NCT07378761

2025-521317-50-00 (EU Trial (CTIS) Number)

RECHMPL24_0328

Details and patient eligibility

About

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.

Enrollment: 94 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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94 participants in 2 patient groups

Experimental arm

Experimental group

Description:

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.

Treatment:

Drug: UDCA (Ursodeoxycholic acid)

Control arm

Active Comparator group

Description:

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.

Treatment:

Drug: Corticosteroids (Reference Treatment)