The primary objective of our study is to determine the efficacy and safety of top-down IFX treatment in moderate-to-severe pediatric CD. Secondary objectives are determination of the pharmacokinetic/-dynamic profile of IFX and finding predictors of…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Clinical remission at 52 weeks without need for additional CD related therapy
or surgery.
Secondary outcome
Secondary efficacy endpoints
* Clinical response (decrease in wPCDAI >17.5) and remission (wPCDAI <12.5)
rates at week 10
* Mucosal healing rates at week 10 assessed by endoscopy (absence of ulcers)
and calprotectin (<100 µg/g), and at week 52 assessed by endoscopy (performed
on a voluntary basis, or if clinically indicated) and/or calprotectin
* Growth (change in height and BMI Z-scores, bone age and pubertal development)
* Quality of life at week14 and 52 (IMPACT III)
* Therapy failure rates over time (primary non-response, loss of response and
medication intolerance)
* Cumulative therapy use (steroids, immunomodulators, biologicals, etc)
Secondary safety endpoints
* Adverse events rates
* Complication rate at 52 weeks (fistulas, abscesses, strictures, surgery,
extra-intestinal manifestations)
Long-term follow-up endpoints (5 years)
* Yearly clinical remission rates without need for additional CD-related
therapy or surgery
* Yearly clinical response, clinical remission and mucosal healing rates
* Number of flairs
* Quality of life at 5 years
* Cumulative therapy use (steroids, immunomodulators, biologicals, etc)
* Adverse events rate
* Complication rate (fistulas, abscesses, strictures, surgery, extra-intestinal
manifestations)
Subanalyses
* Correlation between clinical disease activity, fecal calprotectin and
endoscopic disease severity
* Comparing efficacy and safety endpoints between the two step-up treatment
options (prednisolon+AZA vs EEN+AZA)
Additional objectives
* Determination of PK/PD properties of IFX in children
* Identification of predictive biomarkers of response to IFX
* Comparing cost-efficacy of top-down versus step-up
Background summary
Crohn*s disease (CD) is an incurable, debilitating inflammatory bowel disorder
(IBD) which presents during childhood and adolescence in 25% of its patients.
CD requires lifelong medication and is accompanied by severe complications. The
use of anti-TNF antibodies has significantly improved CD management. Infliximab
(IFX) is the first anti-TNF antibody registered for pediatric CD. Currently,
IFX is reserved for immunomodulator refractory patients. We hypothesize that
top-down IFX use (instead of the current step-up approach) with introduction of
IFX at an early stage of disease, is more effective in the treatment of
pediatric CD patients.
Study objective
The primary objective of our study is to determine the efficacy and safety of
top-down IFX treatment in moderate-to-severe pediatric CD. Secondary objectives
are determination of the pharmacokinetic/-dynamic profile of IFX and finding
predictors of response to IFX in pediatric CD.
Study design
An international multicenter open-label randomised controlled trial
Intervention
Patients will be randomised to either top-down IFX treatment or conventional
step-up treatment.
Treatment arm 1: Top-down IFX treatment will consist of a total of 5 IFX
infusions of 5 mg/kg (IFX induction at week 0, 2 and 6, followed by 2
maintenance infusions every 8 weeks) combined with oral azathioprine (AZA) 2-3
mg/kg once daily. AZA therapy will continue after the last IFX infusion to
maintain remission.
Treatment arm 2: Step-up treatment will consist of standard induction treatment
by either oral prednisolone 1 mg/kg (maximum 40 mg) once daily for 4 weeks,
followed by tapering in 6 weeks until stop, or exclusive enteral nutrition
(EEN) with polymeric feeding for 6 to 8 weeks after which normal foods are
gradually reintroduced within 2-3 weeks. Prednisolone and EEN will be combined
with oral AZA 2-3 mg, once daily, as maintenance treatment.
Study burden and risks
In total, approximately 8 study visits will take place. In 5 of these visits,
additional blood will be drawn for study purposes during routine blood draws
and in case of disease relapse. Patients are requested to collect 3 stool
samples and an additional sample in case of disease relapse. At week 10,
patients will undergo an additional ileocolonoscopy, during which mucosal
biopsies of the ileum and colon will be taken.
The short-term risks of IFX treatment are the risk of infections and
immunogenicity. The
long-term risks of IFX treatment are currently unknown. Some of the patients
randomised to conventional therapy may eventually require and receive IFX, but
in a later stage of the disease.
Top-down treated patients may benefit from increased therapy efficacy with
increased chance of mucosal healing, as demonstrated by earlier studies in
adult CD patients. Increased mucosal healing rates may result in decreased
rates of complications. Since a short disease history and a younger age at
diagnosis have been related to increased IFX efficacy in adults, children may
benefit more from top-down IFX treatment
Wytemaweg 80
Rotterdam 3015 CN
NL
Wytemaweg 80
Rotterdam 3015 CN
NL
Listed location countries
Age
Inclusion criteria
Diagnosed with Crohn's disease,
Moderate-to-severe disease activity
Aged 3-17
Untreated
Exclusion criteria
Need for surgery
Severe comorbidity or severe infection
Active perianal fistulas
Pregnancy
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 | EUCTR2014-005702-37-NL |
| CCMO | NL52030.078.15 |