TISKids: Top-down Infliximab Study in Kids With Crohn's Disease
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Top-down 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. |
Drug: Infliximab
Other Names:
Drug: Azathioprine
Other Names:
|
| Active Comparator: Step-up 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. |
Drug: Prednisolone
Other: Exclusive enteral nutrition
Drug: Azathioprine
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- Clinical response rates [10 weeks]
Response is defined by a decrease in wPCDAI score above 17.5 points compared to baseline
- Clinical remission rates [10 and 52 weeks]
Remission is wPCDAI<12.5
- Mucosal healing [10 and 52 weeks]
Assessed by endoscopy (SES-CD) and/or fecal calprotectin (<100microgram/gram)
- Change in height Z-scores [10 and 52 weeks]
- Change in BMI Z-scores [10 and 52 weeks]
- Change bone age [10 and 52 weeks]
- Change in Tanner stage [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
- Adverse events rates [52 weeks, and 260 weeks]
Adverse events includes therapy side effects, disease complications (fistulas, abscesses, strictures, surgery, extra-intestinal manifestations)
- Cumulative therapy use [52 weeks, and 260 weeks]
- 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 number of flares [260 weeks]
- 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
- Long-term yearly mucosal healing (calprotectin) rates [260 weeks]
fecal calprotectin <100microgram/gram
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Hospital Brussels | Brussels | Belgium | ||
| 2 | University Hospitals Leuven | Leuven | Belgium | ||
| 3 | Helsinki University Central Hospital | Helsinki | Finland | ||
| 4 | Erasmus Medical Center | Rotterdam | Zuid-Holland | Netherlands | 3000 CA |
| 5 | Academic Medical Center | Amsterdam | Netherlands | ||
| 6 | VU University Medical Center | Amsterdam | Netherlands | ||
| 7 | Amphia Hospital | Breda | Netherlands | ||
| 8 | Medisch Spectrum Twente | Enschede | Netherlands | ||
| 9 | Leiden University Medical Center | Leiden | Netherlands | ||
| 10 | Radboud University Medical Center | Nijmegen | Netherlands | ||
| 11 | Maasstad Hospital | Rotterdam | Netherlands | ||
| 12 | University Medical Center Utrecht | Utrecht | Netherlands | ||
| 13 | Isala hospital | Zwolle | Netherlands |
Sponsors and Collaborators
- Erasmus Medical Center
- ZonMw: The Netherlands Organisation for Health Research and Development
- Hospira, now a wholly owned subsidiary of Pfizer
Investigators
- Principal Investigator: Lissy de Ridder, MD PhD, Erasmus Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NL52030.078.15
- 2014-005702-37
- MEC-2015-080