Infliximab Top-down in Pediatric Crohn

Crohn's Disease Clinical Trial

— ITSKids  

Official title:

Infliximab Top-down Study in Kids With Crohn's Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01880307
• Other study ID #: NL39202.078.12
• Secondary ID: 2012-000645-1320
• Status: Terminated
• Phase: Phase 4
• First received: June 7, 2013
• Last updated: July 1, 2015
• Start date: January 2013

Study information

• Verified date: July 2015
• Source: Erasmus Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 13
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years to 17 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

Drug:
• Azathioprine

• Infliximab

• Prednisolon

Locations

Country	Name	City	State
Italy	Sapienza University	Rome
Netherlands	Erasmus Medical Center	Rotterdam	Zuid-Holland

Sponsors (3)

Lead Sponsor	Collaborator
Erasmus Medical Center	Universitair Ziekenhuis Brussel, University of Roma La Sapienza

Countries where clinical trial is conducted

Italy,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pharmacokinetic properties of infliximab		52 weeks	No
Other	Identification of predictive biomarkers of therapy response		52 weeks	No
Other	Correlation between clinical disease activity, fecal calprotectin and endoscopic disease severity		52 weeks	No
Primary	Clinical remission without need for additional CD related therapy or surgery	Clinical remission is defined as a Pediatric Crohn's Disease Activity Index (wPCDAI) score of less than 10 points	52 weeks	No
Secondary	Clinical response and remission rate	Response is defined by a decrease in PCDAI score above 15 points compared to baseline. Remission is PCDAI<10	10 weeks	No
Secondary	Mucosal healing	Assessed by endoscopy (SES-CD) and/or fecal calprotectin (<100microgram/gram)	10 and 52 weeks	No
Secondary	Growth	Change in height and BMI Z-scores, bone age and pubertal development	10 and 52 weeks	No
Secondary	Therapy failure rates over time	Therapy failure: primary non-response, loss of response according to wPCDAI and medication intolerance	52 weeks	No
Secondary	Cumulative therapy use		52 weeks	No
Secondary	Adverse events rates	Adverse events includes therapy side effects, disease complications (fistulas, abscesses, strictures, surgery, extra-intestinal manifestations)	52 weeks	Yes
Secondary	Long-term yearly remission rates without need for additional CD related therapy or surgery		260 weeks	No
Secondary	Long-term yearly clinical remission, response and mucosal healing (calprotectin) rates		260 weeks	No
Secondary	Yearly number of flares		260 weeks	No
Secondary	Cumulative therapy use		260 weeks	No
Secondary	Adverse event rates		260 weeks	Yes

External Links

•   Summary on Medicines for Children Research Network