To compare the effectiveness of weekly subcutaneously administered MTX for maintaining relapse-free sustained steroid/EN-free 1-year remission compared with:- daily oral AZA/6MP in low risk paediatric CD- subcutaneously administered adalimumab in…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Rate of sustained steroid/EEN-free remission at month 12, where sustained
remission is defined as wPCDAI *12.5 and CRP *1,5, fold the normal upper limit
without a relapse since week 12.
Secondary outcome
Comparison between the two treatment arms per risk group (high risk vs low risk
for aggressive disease evolution) (and inter-risk group analysis for
MTX-treated patients) plus analysis of adalimumab-treated patients from
inclusion (TOP-down) versus patients switched to adalimumab due to failure of
immunomodulator therapy (STEP-up).
Background summary
Crohn's disease (CD) is a chronic recurrent inflammatory disorder, which can
cause tissue and bowel damage leading to major disability if not treated
adequately. The recent ECCO-ESPGHAN guidelines indicate that
children/adolescents with a moderate to severe form of Crohn's disease should
receive a more potent treatment regimen allowing to positively influence the
subsequent evolution of the disease. The ultimate aim of treatment is the
control of all inflammation, including at the mucosal level (mucosal healing).
Recent studies suggest that obtaining mucosal healing offers a unique chance
for patients to stop the natural evolution and progression of the disease. This
may translate to a new way of treating CD. A more "aggressive" treatment at
disease onset increases the likelihood of deep remission thereby improving long
term outcomes. Experience with immunomodulators exists for more than 40 years
in the treatment of IBD, and over 15 years with anti-TNF drugs. However, it is
unclear which drug should be used as first line maintenance therapy and for
which patient. A treatment strategy-based clinical trial using a risk-algorithm
to identify high risk patients for progressive disease could address this
question.
Study objective
To compare the effectiveness of weekly subcutaneously administered MTX for
maintaining relapse-free sustained steroid/EN-free 1-year remission compared
with:
- daily oral AZA/6MP in low risk paediatric CD
- subcutaneously administered adalimumab in high risk paediatric CD
Study design
Multicenter, phase IV, prospective, randomized treatment strategy with PROBE
(prospective randomized open blind end-point) evaluation
Intervention
After initial diagnosis of moderate to severe Crohn's disease and an open
induction therapy (exclusive enteral nutrion (orally or by NGT) and/or steroid
therapy) patients are included in this treatment strategy-RCT by week 3 +/-1
and allocated to the high or low risk group for progressive and aggressive
disease course.
In the low risk group: patients are 1:1 randomized to methotrexate versus
azathioprine/6mercaptopurine as maintenance therapy until month 12
In the high risk group: patients are 1:1 randomized to methotrexate versus
adalimumab as maintenance therapy until month 12
Study burden and risks
NA
rue de Sevres 149
Paris 75014
FR
rue de Sevres 149
Paris 75014
FR
Listed location countries
Age
Inclusion criteria
-Children 6-17, with a new-onset CD diagnosed < 6months using established
criteria (28, 29), requiring a steroid-based or EN based induction therapy
-At initial diagnosis, wPCDAI >40 or CRP>2 times upper limit at diagnosis
-all wPCDAI scores (0-120) are possible at inclusion (patients in remission and
patients with active disease)
-Luminal active CD (B1) with or without B2 and/or B3 disease behavior
-Initial exposure to 5-ASA and derivate is tolerated
-Exposure to antibiotics is tolerated
Exclusion criteria
*Patients with wPCDAI<42,5 at initial diagnosis, except if CRP>2 times upper
limit
*No induction therapy with steroids or enteral nutrition
*Previous therapy with any IBD-related medications other than induction therapy
as detailed in this protocol (except 5-ASA).
Design
Recruitment
Medical products/devices used
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 | EUCTR2016-000522-18-NL |
| CCMO | NL59161.078.17 |