Brief Title
Tacrolimus Versus Mycophenolate for Autoimmune Hepatitis Patients With Incomplete Response on First Line Therapy
Official Title
TAILOR Study: Tacrolimus Versus Mycophenolate for Autolmmune Hepatitis Patients With incompLete Response On First Line Therapy: a Randomized Trial
Brief Summary
Rationale: The combination of azathioprine and prednisone is the first-line treatment for
autoimmune hepatitis (AIH), a chronic inflammatory disease of the liver. Complete biochemical
remission (CR) is the first treatment goal in autoimmune hepatitis. CR is determined by AST
and ALT and IgG within the reference range. CR is not reached in a substantial proportion of
AIH patients: after one year 50%, after three years around 20% did not achieve CR. Without CR
ongoing hepatitis leads to progression towards fibrosis and eventually (decompensated)
cirrhosis. Not achieving CR is the most important risk factor for the need for liver
transplantation or liver related death, independent of age and presence of cirrhosis.
Tacrolimus (TAC) and mycophenolate mofetil (MMF) are frequently used to prevent rejection in
kidney and liver transplant patients. In AIH patients with insufficient response or
intolerance to first-line therapy in retrospective cohort studies with MMF 0-57% and with TAC
20-95% CR was reached.
Objective: The aim of this study is to compare the effectiveness of TAC with MMF as a second
line treatment for AIH. Proportion of patients with CR after 12 months of treatment will be
the primary outcome parameter to determine effectivity.
Study design: Randomized open-label two arm study. Patients will be randomized between
treatment with TAC or MMF.
Study population: Patients with AIH with an incomplete response (no CR) to first-line
treatment are eligible for this study.
Intervention: In the TAC group baseline treatment will be replaced by tacrolimus. In the MMF
group baseline treatment will be replaced by MMF. The current dose of prednisolone, or at
least 5 mg daily, will be continued in both arms. After achieving CR prednisolone will be
tapered according to protocol.
Main study parameters/endpoints: Difference in proportion of patients with CR at 12 months
(normalization of ALT, AST and IgG) between the TAC and MMF treatment group.
Secondary parameters:
- Safety and tolerability of TAC and MMF treatments
- Difference in proportion of patients with CR at 6 months (normalization of ALT, AST and
IgG) between the TAC and MMF treatment group.
- Difference in ALT, AST and IgG at 6 and 12 months versus baseline
- Difference in fibrogenesis and fibrosis parameters between groups and before and after
treatment
- Difference in quality of life between groups and before and after treatment
Study Phase
Phase 4
Study Type
Interventional
Primary Outcome
Complete biochemical remission
Secondary Outcome
Safety and Tolerability
Condition
Autoimmune Hepatitis
Intervention
Mycophenolate Mofetil
Study Arms / Comparison Groups
Mycofenolate Mofetil
Description: Patients in the mycophenolate mofetil (MMF) arm will receive MMF for a total of 12 months (if tolerated)
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
86
Start Date
January 19, 2022
Completion Date
January 2024
Primary Completion Date
January 2023
Eligibility Criteria
Inclusion Criteria:
- Patient is older than 18 years old
- Probable or definite auto immune hepatitis according to the original or simplified
IAIHG criteria (>10 points pre-treatment on the original criteria or >6 points on the
simplified criteria)(2, 3)
- Incomplete responder on at least a half year of first-line treatment, with at least
last 6 months azathioprine / 6-MP) / 6-TG and prednisolone or budesonide, and ALT 1.5
- 10x ULN for at least 2 months
- Patient is capable of understanding the purpose and risks of the study, has been fully
informed and has given written informed consent to participate in the study
Exclusion Criteria:
- Presence of decompensated liver disease, defined as ascites, coagulopathy (INR >1.5),
encephalopathy, variceal bleed, hepatopulmonal syndrome, hepatorenal syndrome or HCC
in the past 6 months
- Signs of other liver diseases as NAFLD, Wilson disease, hemochromatosis, alcoholic
liver disease or hepatitis B/C/D
- Clinical diagnosis of overlap / variant syndrome with PBC or PSC
- Liver transplantation in the medical history or currently on the waiting list for
liver transplantation
- Incompliance with therapy during the last 12 months
- Active infections during inclusion including latent tuberculosis and HIV co-infection
- Allergic or hypersensitive to tacrolimus or MMF
- An estimated glomerular filtration rate (eGFR) of <60 mL/min
- Pregnancy or intention to become pregnant in the next 12 months
- Use of TAC or MMF in the past
- Malignancy in the medical history
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Bart van Hoek, +31 6 30 29 11 71, [email protected]
Location Countries
Netherlands
Location Countries
Netherlands
Administrative Informations
NCT ID
NCT05221411
Organization ID
P21.089
Secondary IDs
2021-003420-33
Responsible Party
Principal Investigator
Study Sponsor
Leiden University Medical Center
Study Sponsor
Bart van Hoek, Principal Investigator, Leiden University Medical Center
Verification Date
January 2022