A Multicenter, Randomized, Controlled Trial of Prednisone Combined With Ursodeoxycholic Acid in the Treatment of Primary Biliary Cholangitis With Moderate to Severe Interface Hepatitis Characteristics

Han Ying

Status and phase: Invitation-only; Phase 3; Phase 2

Conditions: Primary Biliary Cholangitis (PBC)

Treatments: Drug: Prednisone; Drug: UDCA (Ursodeoxycholic acid)

Study type: Interventional

Funder types: Other

Identifiers

NCT06591468

KY20242283

Details and patient eligibility

About

About 1/3 of patients with primary biliary cholangitis (PBC) exhibit moderate to severe interface hepatitis, and this group of patients have poor response to UDCA treatment. However, as it is not yet sufficient to diagnose autoimmune hepatitis or overlap syndrome, it is difficult to initiate immunosuppressive therapy such as steroids according to current guidelines. The aim of this study is to explore whether PBC patients with moderate to severe interfacial inflammation can benefit from UDCA combined with prednisone therapy, and its treatment safety.

Enrollment: 244 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Voluntarily joining the group, able to understand and sign an informed consent form;
2. 18 years old ≤ age ≤ 75 years old;
3. The diagnosis of primary biliary cholangitis follows the AASLD international diagnostic and treatment guidelines (meeting two of the following three criteria: AMA or gp210, sp100 positive; Elevated serum ALP levels; Pathological manifestations include non suppurative cholangitis and destruction of the interlobular bile duct;
4. Liver histology suggests moderate to severe interfacial hepatitis (moderate,<50% portal or fibrous septa destruction, severe,>50% portal or fibrous septa destruction) with serum ALT<5 * ULN, serum IgG<2 * ULN, and negative serum anti smooth muscle antibodies;
5. Not receiving UDCA, hormone or other immunosuppressive therapy before enrollment;
6. ALP>1.67 * ULN.

Exclusion criteria

• History or presence of other concomitant liver diseases.
• ALT or 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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244 participants in 2 patient groups

Prednisone

Experimental group

Description:

Combination therapy of UDCA (13-15 mg/kg/day) and prednisone. Prednisone 30-40 mg/day, at 7am in the morning, gradually reduced after 1 month (5mg every 7-14 days) to 5-10 mg for maintenance treatment

UDCA

Active Comparator group

Description:

UDCA (13-15 mg/kg/day)

Treatment:

Drug: UDCA (Ursodeoxycholic acid)