NCT06650124

Induction of Remission in Autoimmune Hepatitis With Azathioprine vs. MMF

• Status: Not Yet Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 108 (estimated)
• Sponsor: Institute of Liver and Biliary Sciences, India · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to determine the effectiveness of azathioprine (AZA) versus mycophenolate mofetil (MMF) in inducing remission in treatment-naive patients with autoimmune hepatitis (AIH). The main questions it aims to answer are: Does MMF combined with prednisolone lead to higher remission rates compared to AZA with prednisolone after 24 weeks? Is MMF associated with fewer adverse events than AZA in these patients? Researchers will compare two treatment arms (MMF vs. AZA) to see if MMF leads to improved remission rates and safety outcomes. Primary Outcome Measure: Biochemical remission: The primary outcome is the normalization of liver enzymes (AST, ALT) and IgG levels at 24 weeks. Secondary Outcome Measures: Safety and adverse events: Monitoring and comparing the incidence and severity of side effects between the two groups. Treatment adherence: Evaluating how well patients stick to their assigned treatment regimens. Improvement in quality of life: Assessing changes in the patient's quality of life using validated questionnaires. Reversal of fibrosis: Measured by liver stiffness using Fibroscan, aiming for no progression of fibrosis. Participants will: Receive either MMF or AZA, alongside a tapering dose of prednisolone. Be monitored regularly through clinic visits, laboratory tests, and safety assessments to track remission and any adverse events.

Detailed description

This clinical trial aims to compare the efficacy and safety of azathioprine (AZA) versus mycophenolate mofetil (MMF) in inducing remission in treatment-naive patients with autoimmune hepatitis (AIH). Autoimmune hepatitis is a chronic liver disease characterized by immune-mediated liver inflammation, leading to liver damage, cirrhosis, or liver failure if untreated. The study will be conducted at the Institute of Liver and Biliary Sciences (ILBS), where eligible patients with AIH will be randomly assigned to one of two treatment groups: AZA Group: Patients will receive azathioprine at an initial dose of 50 mg/day, increased to 100 mg/day after two weeks, combined with a tapering dose of prednisolone. MMF Group: Patients will receive mycophenolate mofetil at an initial dose of 1,000 mg/day, increased to 2,000 mg/day after two weeks, along with a tapering dose of prednisolone. The trial will enroll 108 patients and follow a double-blind, randomized controlled design. The primary endpoint is achieving biochemical remission within 24 weeks, defined by normalizing liver enzymes (AST, ALT) and IgG levels. Secondary endpoints include safety, tolerability, treatment adherence, quality of life, and the prevention or reversal of liver fibrosis (as measured by Fibroscan). The trial's expected duration is one year, with follow-up visits every 4 weeks to monitor patient progress and adverse events. All necessary tests and treatments will follow institutional protocols without additional cost to participants. This study is essential to address the current gaps in AIH treatment, offering critical evidence to guide future clinical decisions on the use of MMF versus AZA for remission induction in AIH.

Conditions

• Autoimmune Hepatitis

Interventions

Type	Name	Description
DRUG	Mycophenolate Mofetil + Prednisolone Participants will receive mycophenolate mofetil in combination.	Participants in this arm will receive mycophenolate mofetil (MMF) starting at 1,000 mg/day for the first two weeks, increasing to 2,000 mg/day thereafter. This will be combined with prednisolone, beginning at 40-60 mg/day, with a tapering dose to 5-10 mg/day after 4-8 weeks, depending on the patient's response. MMF works by inhibiting inosine monophosphate dehydrogenase, which decreases lymphocyte proliferation, thereby reducing immune-mediated liver damage in autoimmune hepatitis. Prednisolone, a corticosteroid, is included to control inflammation during the induction phase of treatment. This intervention lasts for 24 weeks, with monitoring for biochemical remission (normalization of liver enzymes and IgG levels) and adverse events to assess the treatment's safety and efficacy.
DRUG	Azathioprine + Prednisolone	In this arm, participants will receive azathioprine (AZA) starting at 50 mg/day for the first two weeks, followed by an increase to 100 mg/day. This dose will be combined with prednisolone, starting at 40-60 mg/day, with the dosage tapering to 5-10 mg/day after 4-8 weeks, depending on patient response. Azathioprine works as an immunosuppressive agent by inhibiting DNA synthesis in rapidly dividing immune cells, thereby reducing liver inflammation in autoimmune hepatitis. Prednisolone, a corticosteroid, is included to control inflammation during the initial treatment phase. The intervention lasts for 24 weeks with regular monitoring for biochemical remission, defined as normalization of liver enzymes (AST, ALT) and IgG levels, as well as the occurrence of adverse events to assess safety and tolerability.

Timeline

• Start date: 2024-11-01
• Primary completion: 2025-12-31
• Completion: 2025-12-31
• First posted: 2024-10-21
• Last updated: 2024-11-07