Induction of Remission in Autoimmune Hepatitis With Azathioprine vs. MMF

November 5, 2024 updated by: Institute of Liver and Biliary Sciences, India

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

108

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Azathioprine + Prednisolone Arm
Azathioprine + Prednisolone Arm Participants will receive azathioprine (AZA) in combination with prednisolone as part of their treatment regimen.
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.
Active Comparator: Mycophenolate Mofetil + Prednisolone Arm
Mycophenolate Mofetil + Prednisolone Arm Participants will receive mycophenolate mofetil (MMF) in combination with prednisolone as part of their treatment regimen.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Biochemical Remission at 24 Weeks
Time Frame: 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.
24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence and Severity of Adverse Events
Time Frame: 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.
24 weeks.
Treatment Adherence
Time Frame: 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.
24 weeks.
Quality of Life Improvement
Time Frame: 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 life
24 weeks.
Change in Liver Fibrosis
Time Frame: 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.
24 weeks.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institute of Liver and Biliary Sciences, India

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

November 1, 2024

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

October 17, 2024

First Submitted That Met QC Criteria

October 17, 2024

First Posted (Actual)

October 21, 2024

Study Record Updates

Last Update Posted (Estimated)

November 7, 2024

Last Update Submitted That Met QC Criteria

November 5, 2024

Last Verified

October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 12/8/2023-ACAD/E-12745/992

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Investigators currently do not plan to share individual participant data (IPD) from this study. The decision is based on considerations of patient privacy, confidentiality concerns, and the lack of a data-sharing infrastructure. While the aggregated study results will be published and made publicly available, sharing individual-level data could pose risks related to identifying participants. Therefore, IPD will not be shared beyond what is required for regulatory purposes.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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