Clinical Trial: Mycophenolate Mofetil Versus Azathioprine in Treatment Naive Autoimmune Hepatitis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Randomised, Open-label Clinical Trial Assessing the Efficacy and Safety of Mycophenolate Mofetil Versus Azathioprine for Induction of Remission in Treatment Naive Autoimmune He

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 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 bilir

Detailed Summary:
Sponsor: Radboud University

Current Primary Outcome: Biochemical remission [ Time Frame: 24 weeks ]

The percentage of patients in remission, defined as normalization of serum ALT and IgG levels after 24 weeks of treatment, per treatment group.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Time to biochemical remission [ Time Frame: 24 weeks ]
  • Biochemical remission at any time [ Time Frame: Up to 24 weeks ]
  • Partial remission, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) serum levels >1x Upper Limit of Normal (ULN) and <2x ULN [ Time Frame: Up to 24 weeks ]
  • Minimal response, defined as decrease of ALT or AST serum levels but still >2x ULN [ Time Frame: Up to 24 weeks ]
  • Treatment failure, defined as no improvement or increase of ALT or AST serum levels [ Time Frame: Up to 24 weeks ]
  • Changes in liver stiffness, measured by transient elastography [ Time Frame: Up to 24 weeks ]
  • N-terminal procollagen-III-peptide, ELF score [ Time Frame: Up to 24 weeks ]
  • Changes in quality of life measured with Short Form Health survey 36 (SF-36) [ Time Frame: Up to 24 weeks ]
  • Number of patients with treatment related adverse events per treatment group [ Time Frame: Up to 24 weeks ]
  • The level of liver enzymes in both groups [ Time Frame: Up to 24 weeks ]
  • Steroid and other side-effects scores consisting of Visual Analogue Scores (VAS) scores (0 - 10) by the physician for Cushing-face, buffalo hump, acne, striae, bruising and hirsutism. [ Time Frame: Up to 24 weeks ]
  • Percentage of patients with biochemical remission [ Time Frame: Up to 24 weeks ]
  • Ratio of ALT to lowest ALT ever [ Time Frame: Up to 24 weeks ]
  • De novo onset of diabetes mellitus (requiring medication) [ Time Frame: Up to 24 weeks ]
  • Hypertension (requiring medication) [ Time Frame: Up to 24 weeks ]
  • Glaucoma [ Time Frame: Up to 24 weeks ]
  • Number of infections [ Time Frame: Up to 24 weeks ]
  • Extrahepatic AIH manifestations (e.g. arthralgia) [ Time Frame: Up to 24 weeks ]
  • Patient survival [ Time Frame: Up to 24 weeks ]
  • Fatigue index [ Time Frame: Up to 24 weeks ]
  • Pruritis VAS score [ Time Frame: Up to 24 weeks ]
  • Bone fractures [ Time Frame: Up to 24 weeks ]
  • Osteoporosis (confirmed by bone densitometry) [ Time Frame: Up to 24 weeks ]


Original Secondary Outcome: Same as current

Information By: Radboud University

Dates:
Date Received: August 17, 2016
Date Started: January 2017
Date Completion: January 2019
Last Updated: January 9, 2017
Last Verified: August 2016