Top-down Infliximab Study in Kids With Crohn's Disease
- Conditions
- Crohn's Disease
- Interventions
- Registration Number
- NCT02517684
- Lead Sponsor
- Erasmus Medical Center
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 100
- 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
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Step-up Exclusive enteral nutrition 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. Step-up Prednisolone 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. Top-down Infliximab Infliximab and azathioprine; patients will receive 5 infliximab infusions of 5 mg/kg (IFX induction at week 0, 2 and 6, followed by 2 maintenance infusions every 8 weeks). IFX will be discontinued after 5 IFX infusions. Patients will also receive oral azathioprine 2-3 mg/kg, once daily as maintenance treatment. Top-down Azathioprine Infliximab and azathioprine; patients will receive 5 infliximab infusions of 5 mg/kg (IFX induction at week 0, 2 and 6, followed by 2 maintenance infusions every 8 weeks). IFX will be discontinued after 5 IFX infusions. Patients will also receive oral azathioprine 2-3 mg/kg, once daily as maintenance treatment. Step-up Azathioprine 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.
- Primary Outcome Measures
Name Time Method Clinical remission without need for additional CD related therapy or surgery 52 weeks Clinical remission is defined as a weighted Pediatric Crohn's Disease Activity Index (wPCDAI) score of less than 12.5 points
- Secondary Outcome Measures
Name Time Method Change bone age 10 and 52 weeks Change in BMI Z-scores 10 and 52 weeks Change in height Z-scores 10 and 52 weeks Therapy failure rates over time 52 weeks Therapy failure: primary non-response, loss of response according to wPCDAI and medication intolerance
Cumulative therapy use 52 weeks, and 260 weeks Long-term yearly number of flares 260 weeks Clinical remission rates 10 and 52 weeks Remission is wPCDAI\<12.5
Clinical response rates 10 weeks Response is defined by a decrease in wPCDAI score above 17.5 points compared to baseline
Long-term yearly remission rates without need for additional CD related therapy or surgery 260 weeks Clinical remission is defined as a weighted Pediatric Crohn's Disease Activity Index (wPCDAI) score of less than 12.5 points
Long-term yearly clinical remission rates 260 weeks Clinical remission is defined as a weighted Pediatric Crohn's Disease Activity Index (wPCDAI) score of less than 12.5 points
Mucosal healing 10 and 52 weeks Assessed by endoscopy (SES-CD) and/or fecal calprotectin (\<100microgram/gram)
Change in Tanner stage 10 and 52 weeks Adverse events rates 52 weeks, and 260 weeks Adverse events includes therapy side effects, disease complications (fistulas, abscesses, strictures, surgery, extra-intestinal manifestations)
Long-term yearly mucosal healing (calprotectin) rates 260 weeks fecal calprotectin \<100microgram/gram
Trial Locations
- Locations (13)
Academic Medical Center
🇳🇱Amsterdam, Netherlands
Amphia Hospital
🇳🇱Breda, Netherlands
Radboud University Medical Center
🇳🇱Nijmegen, Netherlands
University Hospital Brussels
🇧🇪Brussels, Belgium
Erasmus Medical Center
🇳🇱Rotterdam, Zuid-Holland, Netherlands
Medisch Spectrum Twente
🇳🇱Enschede, Netherlands
Helsinki University Central Hospital
🇫🇮Helsinki, Finland
Maasstad Hospital
🇳🇱Rotterdam, Netherlands
VU University Medical Center
🇳🇱Amsterdam, Netherlands
Leiden University Medical Center
🇳🇱Leiden, Netherlands
University Hospitals Leuven
🇧🇪Leuven, Belgium
Isala hospital
🇳🇱Zwolle, Netherlands
University Medical Center Utrecht
🇳🇱Utrecht, Netherlands