Induction of Remission in Autoimmune Hepatitis With Azathioprine vs. MMF
- Conditions
- Autoimmune Hepatitis
- Interventions
- Registration Number
- NCT06650124
- Lead Sponsor
- Institute of Liver and Biliary Sciences, India
- Brief 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 108
Diagnosis: Confirmed diagnosis of autoimmune hepatitis (AIH) based on clinical, biochemical, and histological findings.
Biochemical markers: Elevated liver enzymes, specifically AST and ALT, indicating liver inflammation.
Treatment-naive: Patients must be treatment-naive, meaning they have not received prior immunosuppressive therapy for AIH.
Willingness to participate: Patients must provide informed consent and be willing to comply with all study-related procedures and follow-ups. -
- Acute liver failure: Patients presenting with acute liver failure at baseline will be excluded.
Other liver diseases: Co-existing liver conditions such as hepatitis B, hepatitis C, primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), or any alcohol-induced liver disease will lead to exclusion.
Low blood counts: Patients with a platelet count less than 50,000/mm³ or total leukocyte count (TLC) less than 3,000/mm³ will not be eligible.
Previous treatment: Patients who have already received immunosuppressive or disease-modifying therapy for AIH or related conditions.
Pregnancy or lactation: Pregnant or lactating women will be excluded to avoid potential risks to the mother or fetus.
Hepatocellular carcinoma (HCC) or malignancy: Any patients with evidence of hepatocellular carcinoma or other active malignancies.
Medication allergies: Patients with known allergies to azathioprine, mycophenolate mofetil (MMF), or prednisolone will be excluded.
Non-consent: Patients who are not willing to participate in the study or unable to provide informed consent.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Mycophenolate Mofetil + Prednisolone Arm Mycophenolate Mofetil + Prednisolone Participants will receive mycophenolate mofetil in combination. Mycophenolate Mofetil + Prednisolone Arm Participants will receive mycophenolate mofetil (MMF) in combination with prednisolone as part of their treatment regimen. Azathioprine + Prednisolone Arm Azathioprine + Prednisolone Azathioprine + Prednisolone Arm Participants will receive azathioprine (AZA) in combination with prednisolone as part of their treatment regimen.
- Primary Outcome Measures
Name Time Method Biochemical Remission at 24 Weeks 24 weeks Definition: Normalization of liver enzymes (ALT, AST) and immunoglobulin G (IgG) levels.
Time Frame: Measured at 24 weeks of treatment. Purpose: To evaluate the effectiveness of mycophenolate mofetil (MMF) versus azathioprine (AZA) in achieving biochemical remission in treatment-naive autoimmune hepatitis (AIH) patients.
- Secondary Outcome Measures
Name Time Method Incidence and Severity of Adverse Events 24 weeks. Definition: Number and severity (mild, moderate, or severe) of adverse events related to the treatment.
Time Frame: Assessed at each follow-up visit (every 4 weeks) during the 24-week treatment period.
Purpose: To compare the safety profiles of MMF and AZA.Treatment Adherence 24 weeks. Definition: Percentage of participants who complete the 24-week treatment without discontinuation due to adverse events or non-compliance.
Time Frame: Measured throughout the 24-week period. Purpose: To assess patient adherence to treatment protocols in both groups.Quality of Life Improvement 24 weeks. Definition: Change in the quality of life score based on a validated patient-reported outcome questionnaire, SF-36, and CLDQ.
Time Frame: Measured at baseline and 24 weeks. Purpose: To determine whether improvements in liver function correlate with better quality of lifeChange in Liver Fibrosis 24 weeks. Definition: Change in liver fibrosis stage, measured by Fibroscan. Time Frame: Measured at baseline and 24 weeks. Purpose: To evaluate if either treatment leads to a reduction in liver fibrosis or prevents its progression.