Crohn's Disease
Conditions
Keywords
Crohn's disease, pediatric, infliximab, top-down, ITSKids
Brief summary
The purpose of this study is to determine whether a top-down treatment approach, prescribing infliximab and azathioprine at diagnose, yields better outcome in comparison to the usual step-up treatment approach, starting with prednison and azathioprine, in moderate-to-severe pediatric Crohn's disease (CD) patients.
Detailed description
Objective: The purpose of this study is to determine whether a top-down treatment approach, prescribing infliximab and azathioprine at diagnose, yields better outcome in comparison to the usual step-up treatment approach, starting with prednison and azathioprine, in moderate-to-severe pediatric Crohn's disease (CD) patients. Sample size: We will include 100 (2 x 50) patients. With these numbers a difference of 60% and 85% (= 25) can be shown at a power of 80% (2-sided α 0.05; nQuery Advisor). Study design: an international open-label randomised controlled trial Study population: Children (age 3-17 yrs) with new-onset, untreated, CD with moderate-to-severe disease activity 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 oral prednisolone 1 mg/kg (maximum 40 mg) once daily for 4 weeks, followed by tapering in 6 weeks until stop. Prednisolone will be combined with oral AZA 2-3 mg, once daily, as maintenance treatment. Main study parameters/endpoints: Clinical remission at 52 weeks without need for additional IBD related therapy or surgery. Secondary endpoints include clinical response, remission and mucosal healing at week 10 and 52, growth and adverse events.
Interventions
Sponsors
University of Roma La Sapienza
Universitair Ziekenhuis Brussel
Erasmus Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
Children (age 3-17 years, both male and female) with new-onset, untreated CD with moderate-to-severe disease activity assessed by a wPCDAI \>40 will be eligible for inclusion after a diagnosis of CD was made based on the Porto criteria.
Exclusion criteria
Patients with the following characteristics will be excluded: immediate need for surgery, symptomatic stenosis or stricture in the bowel due to scarring, active perianal fistulas, severe co-morbidity, severe infection such as sepsis or opportunistic infections, positive stool culture, positive Clostridium difficile assay, positive tuberculin test or a chest radiograph consistent with tuberculosis or malignancy, those already started with CD specific therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical remission without need for additional CD related therapy or surgery | 52 weeks | Clinical remission is defined as a Pediatric Crohn's Disease Activity Index (wPCDAI) score of less than 10 points |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mucosal healing | 10 and 52 weeks | Assessed by endoscopy (SES-CD) and/or fecal calprotectin (\<100microgram/gram) |
| Long-term yearly clinical remission, response and mucosal healing (calprotectin) rates | 260 weeks | — |
| Yearly number of flares | 260 weeks | — |
| Adverse event rates | 260 weeks | — |
| Long-term yearly remission rates without need for additional CD related therapy or surgery | 260 weeks | — |
| Adverse events rates | 52 weeks | Adverse events includes therapy side effects, disease complications (fistulas, abscesses, strictures, surgery, extra-intestinal manifestations) |
| Clinical response and remission rate | 10 weeks | Response is defined by a decrease in PCDAI score above 15 points compared to baseline. Remission is PCDAI\<10 |
| Cumulative therapy use | 52 weeks | — |
| Growth | 10 and 52 weeks | Change in height and BMI Z-scores, bone age and pubertal development |
| Therapy failure rates over time | 52 weeks | Therapy failure: primary non-response, loss of response according to wPCDAI and medication intolerance |
Other
| Measure | Time frame |
|---|---|
| Identification of predictive biomarkers of therapy response | 52 weeks |
| Correlation between clinical disease activity, fecal calprotectin and endoscopic disease severity | 52 weeks |
| Pharmacokinetic properties of infliximab | 52 weeks |
Countries
Italy, Netherlands
Outcome results
None listed