Tacrolimus Versus Mycophenolate for Autoimmune Hepatitis Patients With Incomplete Response on First Line Therapy

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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