Mycophenolate Mofetil Versus Azathioprine in Treatment Naive Autoimmune Hepatitis

NCT ID: NCT02900443

Last Updated: 2023-06-22

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-31
• Study Completion Date: 2023-06-30

Brief Summary

Rationale: Current standard therapy of autoimmune hepatitis consists of a combination of prednisolone and azathioprine. However, a significant proportion of patients does not respond to, or is intolerant for, azathioprine. Mycophenolate mofetil (MMF) has surpassed azathioprine as therapy to prevent organ transplant rejection and is sometimes used as an alternative option for autoimmune hepatitis. Several case series and one prospective study have documented the efficacy and safety of mycophenolate mofetil as induction therapy for autoimmune hepatitis. Robust evidence from a formal randomized clinical trial is lacking.

Objective: To assess the efficacy and safety of mycophenolate mofetil as induction therapy in patients with treatment naive autoimmune hepatitis.

Study design: Multicenter, randomised, open-label intervention study Study population: Patients with newly diagnosed autoimmune hepatitis who are in need of induction therapy according to current guidelines.

Intervention: The intervention group will receive oral mycophenolate mofetil for 24 weeks. The control group will be treated with azathioprine for 24 weeks. Both groups will be treated with steroid induction which will closely follow the schedule from the recent Clinical Practice Guidelines by the European Association for Study of the Liver (EASL).

Main study parameters/endpoints: The primary outcome is the proportion of patients in biochemical remission, defined as normalization of serum alanine transaminase (ALT) and immunoglobulin G (IgG) levels after 24 weeks of treatment, per treatment group. Secondary endpoints include safety and tolerability of mycophenolate mofetil, time to remission, changes in Model For End-Stage Liver Disease (MELD) -score (and its components bilirubin, INR, creatinine), albumin, pseudocholinesterase and N-terminal procollagen-III-peptide, ELF (Enhanced Liver Fibrosis) -score and aspects of quality of life.

Conditions

Autoimmune Hepatitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Mycophenolate mofetil

The intervention group will receive oral mycophenolate mofetil for 24 weeks. Both groups will be treated with steroid induction which will closely follow the schedule from the recent EASL Clinical Practice Guidelines.

Group Type: EXPERIMENTAL

Mycophenolate mofetil

Intervention Type: DRUG

Azathioprine

. The control group will be treated with azathioprine (standard of care) for 24 weeks. Both groups will be treated with steroid induction which will closely follow the schedule from the recent EASL Clinical Practice Guidelines.

Group Type: ACTIVE_COMPARATOR

Azathioprine

Intervention Type: DRUG

Interventions

Mycophenolate mofetil

Intervention Type: DRUG

Azathioprine

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Probable or definite diagnosis of autoimmune hepatitis according to the International Autoimmune Hepatitis Study Group criteria
• First presentation of AIH requiring treatment according to the current EASL guidelines
• Age ≥ 18 years
• Must provide informed consent and agree to comply with the trial protocol

Exclusion Criteria

• Overlap syndrome with Primary Sclerosing Cholangitis (PSC) or Primary Biliary Cholangitis (PBC) (Paris criteria, strong positive Anti-Mitochondrial Antibodies (AMA), past liver biopsy or cholangiographic findings compatible with PBC or PSC).
• Presentation with acute liver failure, defined as presence of hepatic encephalopathy and coagulopathy (INR > 1.5)
• Current treatment with prednisone/prednisolone and/or immunosuppressive medication for an indication other than autoimmune hepatitis
• Current systemic infection
• Other clinically significant medical conditions that could interfere with the trial
• If female of childbearing potential: known pregnancy, or unwilling to practice anticontraceptive measures.
• History of noncompliance with medical regimens, or patients who are considered to be potentially unreliable or unable to participate
• Mental instability or incompetence, such that the validity of informed consent or compliance with the trial is uncertain

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Leiden University Medical Center

OTHER

Sponsor Role: collaborator

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bart van Hoek, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center

Joost PH Drenth, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Locations

University Hospital Antwerpen

Antwerp, , Belgium

Zuyderland

Heerlen, Limburg, Netherlands

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, , Netherlands

Vrije Universiteit Medisch Centrum

Amsterdam, , Netherlands

Amsterdam UMC, location AMC

Amsterdam, , Netherlands

Rijnstate Ziekenhuis

Arnhem, , Netherlands

Medisch Spectrum Twente

Enschede, , Netherlands

University Medical Center Groningen

Groningen, , Netherlands

Leiden University Medical Centre

Leiden, , Netherlands

Maastricht UMC+

Maastricht, , Netherlands

Sint Antonius Hospital

Nieuwegein, , Netherlands

Radboud University Medical Centre

Nijmegen, , Netherlands

Erasmus MC

Rotterdam, , Netherlands

Bernhoven

Uden, , Netherlands

Countries

Belgium; Netherlands

References

Snijders RJALM, Stoelinga AEC, Gevers TJG, Pape S, Biewenga M, Tushuizen ME, Verdonk RC, de Jonge HJM, Vrolijk JM, Bakker SF, Vanwolleghem T, de Boer YS, Baven Pronk MAMC, Beuers U, van der Meer AJ, Gerven NMFV, Sijtsma MGM, van Eijck BC, van IJzendoorn MC, van Herwaarden M, van den Brand FF, Korkmaz KS, van den Berg AP, Guichelaar MMJ, Levens AD, van Hoek B, Drenth JPH; Dutch Autoimmune Hepatitis Working Group. An open-label randomised-controlled trial of azathioprine vs. mycophenolate mofetil for the induction of remission in treatment-naive autoimmune hepatitis. J Hepatol. 2024 Apr;80(4):576-585. doi: 10.1016/j.jhep.2023.11.032. Epub 2023 Dec 14.

Reference Type: DERIVED

PMID: 38101756 (View on PubMed)

Other Identifiers

NL57115.058.16

Identifier Type: -

Identifier Source: org_study_id