To assess the efficacy and safety of mycophenolate mofetil as induction therapy in patients with treatment naive autoimmune hepatitis.
ID
Source
Brief title
Condition
- Hepatic and hepatobiliary disorders
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome is the proportion of patients in remission, defined as
normalization of serum ALT and IgG levels after 24 weeks of treatment, per
treatment group. Secondary endpoints include safety and tolerability of
mycophenolate mofetil, time to remission, changes in MELD-score (and its
components bilirubine, INR, creatinine), albumin, pseudocholinesterase and
N-terminal procollagen-III-peptide, ELF-score and aspects of quality of life.
In a sub-study, drug levels will be measured.
Secondary outcome
A. Biochemical remission at 24 weeks and at anytime
B. Time to biochemical remission
C. Partial remission, defined as ALT and AST serum levels >1x ULN and <2x ULN
D. Minimal response, defined as decrease of ALT and AST serum levels but still
>2x ULN
E. Treatment failure, defined as no improvement or increase of ALT and AST
serum levels
F. Changes in MELD score (and its components bilirubin, INR, creatinine) and in
albumin and pseudocholinesterase
G. N-terminal procollagen-III-peptide, ELF score
H. Changes in quality of life measured with SF-36
I. Assessment of safety of MMF versus AZA in patients with AIH
J. The level of ALT, AST, GGT in both groups
K. Steroid and other side-effects scores consisting of VAS scores (0 - 10) by
the physician for Cushing-face, buffalo hump, acne, striae, bruising and
hirsutism.
L. Percentage of patients with biochemical remission
M. Ratio of ALAT to lowest ALAT ever
N. Mood alterations, headache, insomnia
O. Diabetes (requiring medication)
P. Hypertension (requiring medication)
Q. Bone fractures, osteoporosis and muscular weakness
R. Glaucoma and increased intraocular pressure
S. Number of infections
T. Extrahepatic AIH manifestations (e.g. arthralgia)
U. Patient survival
V. Fatigue index
W. Pruritis VAS score
Background summary
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.
Study 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
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 EASL Clinical Practice Guidelines.
Study burden and risks
The burden of the study consists of extra blood samples. Randomisation will be
in a 1:1 ratio and patients will be treated with azathioprine, which is the
current standard of care or mycophenolate mofetil. In both arms the standard
prednisolone schedule is given. The potential benefit for participating
patients is that mycophenolate mofetil may be more effective as induction
therapy in autoimmune hepatitis and may possibly have less side-effects.
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
1. Probable or definite diagnosis of autoimmune hepatitis according to the
International Autoimmune Hepatitis Study Group criteria (table 2) 9:
• Definite autoimmune hepatitis: >= 7
• Probable autoimmune hepatitis >= 6
2. First presentation of AIH requiring treatment according to the current EASL
guidelines
3. Age >= 18 years
4. Must provide informed consent and agree to comply with the trial protocol
Exclusion criteria
1. Overlap syndrome with PSC or PBC (Paris criteria 29, strong positive AMA,
past liver biopsy or cholangiographic findings compatible with PBC or PSC).2.
Presence of clinical significant hepatic decompensation including:• History of
liver transplantation, current active placement on a liver transplant waiting
list.
• Portal hypertension with complications including: poorly controlled or
diuretic resistant ascites, history of variceal bleeding or related therapeutic
interventions (e.g. variceal banding, transjugular intrahepatic portosystemic
shunts) or hepatic encephalopathy.
• Cirrhosis with complications, including history or presence of: spontaneous
bacterial peritonitis, hepatocellular carcinoma, hepatorenal syndrome
a. N.B. cirrhosis without complications as mentioned above, is not an exclusion
criterion
3. Current treatment with predniso(lo)ne and/or immunosuppressive medication
for an indication other than autoimmune hepatitis4. Current systemic
infection5. Other clinically significant medical conditions that could
interfere with the trial6. If female of childbearing potential: known
pregnancy, or unwilling to practice anticontraceptive measures. 7. History of
noncompliance with medical regimens, or patients who are considered to be
potentially unreliable or unable to participate8. Mental instability or
incompetence, such that the validity of informed consent or compliance with the
trial is uncertain
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-001038-91-NL |
| ClinicalTrials.gov | NCT02900443 |
| CCMO | NL57115.058.16 |