MedTrace Logo

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

NCT05221411 · Status: UNKNOWN · Phase: PHASE4 · Type: INTERVENTIONAL · Enrollment: 86

Last updated 2022-02-03

No results posted yet for this study

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

Conditions

  • Autoimmune Hepatitis

Interventions

DRUG

Mycophenolate Mofetil

Mycophenolate mofetil will be started at a dose 500mg twice daily. When tolerated and an AUC within range, patients will be titrated to 1000mg twice daily at week two.

DRUG

Tacrolimus

Meltdose tacrolimus will be started at a dose of 0.07 mg/kg/day. The drug will be taken orally once-daily in the morning. Dose will be adjusted to reach target AUC and trough levels.

Sponsors & Collaborators

  • Leiden University Medical Center

    lead OTHER

Principal Investigators

  • Bart van Hoek · Leiden University Medical Center

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
PARALLEL

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2022-01-19
Primary Completion
2023-01-31
Completion
2024-01-31

Countries

  • Netherlands

Study Locations

More Related Trials

Entities

Drugs

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT05221411 on ClinicalTrials.gov