Mycophenolate Mofetil Versus Azathioprine in Treatment Naive Autoimmune Hepatitis

Autoimmune Hepatitis Clinical Trial

— CAMARO  

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 Hepatitis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02900443
• Other study ID #: NL57115.058.16
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: January 2017
• Est. completion date: June 2023

Study information

• Verified date: October 2021
• Source: Radboud University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 70
• Est. completion date: June 2023
• Est. primary completion date: June 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Autoimmune Hepatitis
• Hepatitis
• Hepatitis A
• Hepatitis, Autoimmune

Intervention

Drug:
• Mycophenolate mofetil

• Azathioprine

Locations

Country	Name	City	State
Belgium	University Hospital Antwerpen	Antwerpen
Netherlands	Amsterdam UMC, location AMC	Amsterdam
Netherlands	Vrije Universiteit Medisch Centrum	Amsterdam
Netherlands	Rijnstate Ziekenhuis	Arnhem
Netherlands	Jeroen Bosch Ziekenhuis	Den Bosch
Netherlands	Medisch Spectrum Twente	Enschede
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Zuyderland	Heerlen	Limburg
Netherlands	Leiden University Medical Centre	Leiden
Netherlands	Maastricht UMC+	Maastricht
Netherlands	Sint Antonius Hospital	Nieuwegein
Netherlands	Radboud University Medical Centre	Nijmegen
Netherlands	Erasmus MC	Rotterdam
Netherlands	Bernhoven	Uden

Sponsors (2)

Lead Sponsor	Collaborator
Radboud University Medical Center	Leiden University Medical Center

Countries where clinical trial is conducted

Belgium,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Biochemical remission	The percentage of patients in biochemical remission, defined as normalization of serum ALT and IgG levels after 24 weeks of treatment, per treatment group.	24 weeks
Secondary	Time to biochemical remission		24 weeks
Secondary	Biochemical remission at any time		Up to 24 weeks
Secondary	Complete biochemical response, defined as normalization of AST, ALT and IgG at 6 months after initiation of treatment		Up to 24 weeks
Secondary	Insufficient response, defined as lack of complete biochemical response determined at 6 months		Up to 24 weeks
Secondary	Non-response at 4 weeks: defined as <50% decrease of serum transaminases within 4 weeks after initiation of treatment		Up to 4 weeks
Secondary	Changes in MELD score (and its components bilirubin, international normalized ratio (INR), creatinine) and in albumin		Up to 24 weeks
Secondary	Changes in liver stiffness, measured by transient elastography		Up to 24 weeks
Secondary	N-terminal procollagen-III-peptide, ELF score		24 weeks
Secondary	Changes in quality of life measured with SF-36		Up to 24 weeks
Secondary	Difference in side-effects, adverse events and serious adverse events		Up to 24 weeks
Secondary	The level of ALT, AST, GGT in both groups		Up to 24 weeks
Secondary	Percentage of patients with biochemical remission		Up to 24 weeks
Secondary	Ratio of ALT to lowest ALT ever		Up to 24 weeks
Secondary	Extrahepatic AIH manifestations (e.g. arthralgia)		Up to 24 weeks
Secondary	Patient survival		Up to 24 weeks
Secondary	Fatigue index		Up to 24 weeks
Secondary	Pruritis VAS score		Up to 24 weeks
Secondary	Difference in cumulative corticosteroid dose between MMF and azathioprine		Up to 24 weeks