Clinical trial NCT01880307: Infliximab Top-down in Pediatric Crohn
Official title: Infliximab Top-down Study in Kids With Crohn's Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Crohn's Disease
Keywords: Crohn's disease
pediatric
infliximab
top-down
ITSKids
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
Collaborators: name: University of Roma La Sapienza
name: Universitair Ziekenhuis Brussel
First posted: 2013-06-18
Enrollment: 13
Sex: ALL
Minimum age (years): 3
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Clinical remission without need for additional CD related therapy or surgery
timeFrame: 52 weeks
Secondary outcomes:
measure: Clinical response and remission rate
timeFrame: 10 weeks
measure: Mucosal healing
timeFrame: 10 and 52 weeks
measure: Growth
timeFrame: 10 and 52 weeks
measure: Therapy failure rates over time
timeFrame: 52 weeks
measure: Cumulative therapy use
timeFrame: 52 weeks
measure: Adverse events rates
timeFrame: 52 weeks
measure: Long-term yearly remission rates without need for additional CD related therapy or surgery
timeFrame: 260 weeks
measure: Long-term yearly clinical remission, response and mucosal healing (calprotectin) rates
timeFrame: 260 weeks
measure: Yearly number of flares
timeFrame: 260 weeks
measure: Cumulative therapy use
timeFrame: 260 weeks
measure: Adverse event rates
timeFrame: 260 weeks
Other outcomes:
measure: Pharmacokinetic properties of infliximab
timeFrame: 52 weeks
measure: Identification of predictive biomarkers of therapy response
timeFrame: 52 weeks
measure: Correlation between clinical disease activity, fecal calprotectin and endoscopic disease severity
timeFrame: 52 weeks
Locations:
city: Rome
country: Italy
facility: Sapienza University
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
state: Zuid-Holland
Study officials:
affiliation: Erasmus Medical Center
name: Lissy Ridder, de, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: