Mycophenolate Mofetil Versus Azathioprine in Treatment Naive Autoimmune Hepatitis
- Registration Number
- NCT02900443
- Lead Sponsor
- Radboud University Medical Center
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 70
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Mycophenolate mofetil 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. Azathioprine 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.
- Primary Outcome Measures
Name Time Method Biochemical remission 24 weeks The percentage of patients in biochemical remission, defined as normalization of serum ALT and IgG levels after 24 weeks of treatment, per treatment group.
- Secondary Outcome Measures
Name Time Method Fatigue index Up to 24 weeks Patient survival Up to 24 weeks Pruritis VAS score Up to 24 weeks Complete biochemical response, defined as normalization of AST, ALT and IgG at 6 months after initiation of treatment Up to 24 weeks Time to biochemical remission 24 weeks Percentage of patients with biochemical remission Up to 24 weeks Ratio of ALT to lowest ALT ever Up to 24 weeks Biochemical remission at any time Up to 24 weeks Changes in liver stiffness, measured by transient elastography Up to 24 weeks N-terminal procollagen-III-peptide, ELF score 24 weeks The level of ALT, AST, GGT in both groups Up to 24 weeks Changes in quality of life measured with SF-36 Up to 24 weeks Extrahepatic AIH manifestations (e.g. arthralgia) Up to 24 weeks Difference in cumulative corticosteroid dose between MMF and azathioprine Up to 24 weeks Insufficient response, defined as lack of complete biochemical response determined at 6 months Up to 24 weeks Non-response at 4 weeks: defined as <50% decrease of serum transaminases within 4 weeks after initiation of treatment Up to 4 weeks Changes in MELD score (and its components bilirubin, international normalized ratio (INR), creatinine) and in albumin Up to 24 weeks Difference in side-effects, adverse events and serious adverse events Up to 24 weeks
Trial Locations
- Locations (14)
Jeroen Bosch Ziekenhuis
🇳🇱Den Bosch, Netherlands
University Hospital Antwerpen
🇧🇪Antwerpen, Belgium
Vrije Universiteit Medisch Centrum
🇳🇱Amsterdam, Netherlands
Amsterdam UMC, location AMC
🇳🇱Amsterdam, Netherlands
Bernhoven
🇳🇱Uden, Netherlands
Medisch Spectrum Twente
🇳🇱Enschede, Netherlands
Leiden University Medical Centre
🇳🇱Leiden, Netherlands
Sint Antonius Hospital
🇳🇱Nieuwegein, Netherlands
Maastricht UMC+
🇳🇱Maastricht, Netherlands
Erasmus MC
🇳🇱Rotterdam, Netherlands
Rijnstate Ziekenhuis
🇳🇱Arnhem, Netherlands
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Radboud University Medical Centre
🇳🇱Nijmegen, Netherlands
Zuyderland
🇳🇱Heerlen, Limburg, Netherlands