Clinical trial NCT02517684: Top-down Infliximab Study in Kids With Crohn's Disease
Official title: Top-down Infliximab Study in Kids With Crohn's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Crohn's Disease
Keywords: Crohn's disease
pediatric
infliximab
top-down
TISKids
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
name: Hospira, now a wholly owned subsidiary of Pfizer
First posted: 2015-08-07
Enrollment: 100
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 (IFX) and azathioprine (AZA) at diagnose, yields better outcome in comparison to the usual step-up treatment approach, starting with prednison and AZA or exclusive enteral nutrition (EEN) and AZA, 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 IFX and AZA at diagnose, yields better outcome in comparison to the usual step-up treatment approach, starting with prednison and AZA or EEN and AZA, in moderate-to-severe pediatric 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).

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 (weighted Pediatric CD Index \[wPCDAI\] \>40) Intervention: Patients will be randomised to either top-down 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 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 EEN with polymeric feeding for 6-8 weeks after which normal foods are gradually reintroduced within 2-3 weeks. Either of these induction treatments 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 CD related therapy or surgery. Secondary endpoints include clinical response, remission and mucosal healing at week 10 and 52, growth, quality of life and adverse events.

Eligibility criteria: Inclusion Criteria:

* Children (age 3-17 years, both male and female, weight \>10kg) 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,
* patients with a suspected or
* definitive pregnancy

Primary outcomes:
measure: Clinical remission without need for additional CD related therapy or surgery
timeFrame: 52 weeks
Secondary outcomes:
measure: Clinical response rates
timeFrame: 10 weeks
measure: Clinical remission rates
timeFrame: 10 and 52 weeks
measure: Mucosal healing
timeFrame: 10 and 52 weeks
measure: Change in height Z-scores
timeFrame: 10 and 52 weeks
measure: Change in BMI Z-scores
timeFrame: 10 and 52 weeks
measure: Change bone age
timeFrame: 10 and 52 weeks
measure: Change in Tanner stage
timeFrame: 10 and 52 weeks
measure: Therapy failure rates over time
timeFrame: 52 weeks
measure: Adverse events rates
timeFrame: 52 weeks, and 260 weeks
measure: Cumulative therapy use
timeFrame: 52 weeks, and 260 weeks
measure: Long-term yearly remission rates without need for additional CD related therapy or surgery
timeFrame: 260 weeks
measure: Long-term yearly number of flares
timeFrame: 260 weeks
measure: Long-term yearly clinical remission rates
timeFrame: 260 weeks
measure: Long-term yearly mucosal healing (calprotectin) rates
timeFrame: 260 weeks
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: University Hospital Brussels
city: Leuven
country: Belgium
facility: University Hospitals Leuven
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
state: Zuid-Holland
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Amsterdam
country: Netherlands
facility: VU University Medical Center
city: Breda
country: Netherlands
facility: Amphia Hospital
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
city: Rotterdam
country: Netherlands
facility: Maasstad Hospital
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Zwolle
country: Netherlands
facility: Isala hospital
Study officials:
affiliation: Erasmus Medical Center
name: Lissy de Ridder, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jongsma MME, Aardoom MA, Cozijnsen MA, van Pieterson M, de Meij T, Groeneweg M, Norbruis OF, Wolters VM, van Wering HM, Hojsak I, Kolho KL, Hummel T, Stapelbroek J, van der Feen C, van Rheenen PF, van Wijk MP, Teklenburg-Roord STA, Schreurs MWJ, Rizopoulos D, Doukas M, Escher JC, Samsom JN, de Ridder L. First-line treatment with infliximab versus conventional treatment in children with newly diagnosed moderate-to-severe Crohn's disease: an open-label multicentre randomised controlled trial. Gut. 2022 Jan;71(1):34-42. doi: 10.1136/gutjnl-2020-322339. Epub 2020 Dec 31.
citation: Cozijnsen MA, van Pieterson M, Samsom JN, Escher JC, de Ridder L. Top-down Infliximab Study in Kids with Crohn's disease (TISKids): an international multicentre randomised controlled trial. BMJ Open Gastroenterol. 2016 Dec 22;3(1):e000123. doi: 10.1136/bmjgast-2016-000123. eCollection 2016.