Clinical trial NCT06650124: Induction of Remission in Autoimmune Hepatitis With Azathioprine vs. MMF
Official title: Induction of Remission in Autoimmune Hepatitis With Azathioprine vs. MMF
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Autoimmune Hepatitis
Keywords: utoimmune Hepatitis (AIH)
Azathioprine (AZA)
Mycophenolate Mofetil (MMF)
Induction of Remission
Lead sponsor: Institute of Liver and Biliary Sciences, India
Sponsor class: OTHER
First posted: 2024-10-21
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: nterventional Study Model: Parallel Assignment Study Type: Interventional (Clinical Trial) Study Model: Parallel Assignment - Participants are randomly assigned to one of two groups (either receiving azathioprine or mycophenolate mofetil) and remain in their assigned group for the entire study.

Masking: Double-blind (both participants and investigators are unaware of which treatment is being administered to prevent bias).

Allocation: Randomized - Patients are randomly allocated to one of the two treatment groups.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

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. -

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Biochemical Remission at 24 Weeks
timeFrame: 24 weeks
Secondary outcomes:
measure: Incidence and Severity of Adverse Events
timeFrame: 24 weeks.
measure: Treatment Adherence
timeFrame: 24 weeks.
measure: Quality of Life Improvement
timeFrame: 24 weeks.
measure: Change in Liver Fibrosis
timeFrame: 24 weeks.
Other outcomes:
Locations:
Study officials:
References:
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