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

Crohn's Disease Clinical Trial

— TISKids  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02517684
• Other study ID #: NL52030.078.15
• Secondary ID: 2014-005702-37ME
• Status: Completed
• Phase: Phase 4
• Start date: April 2015
• Est. completion date: January 2024

Study information

• Verified date: March 2024
• Source: Erasmus Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: January 2024
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

Drug:
• Infliximab

• Prednisolone

Other:
• Exclusive enteral nutrition

Drug:
• Azathioprine

Locations

Country	Name	City	State
Belgium	University Hospital Brussels	Brussels
Belgium	University Hospitals Leuven	Leuven
Finland	Helsinki University Central Hospital	Helsinki
Netherlands	Academic Medical Center	Amsterdam
Netherlands	VU University Medical Center	Amsterdam
Netherlands	Amphia Hospital	Breda
Netherlands	Medisch Spectrum Twente	Enschede
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Radboud University Medical Center	Nijmegen
Netherlands	Erasmus Medical Center	Rotterdam	Zuid-Holland
Netherlands	Maasstad Hospital	Rotterdam
Netherlands	University Medical Center Utrecht	Utrecht
Netherlands	Isala hospital	Zwolle

Sponsors (3)

Lead Sponsor	Collaborator
Erasmus Medical Center	Hospira, now a wholly owned subsidiary of Pfizer, ZonMw: The Netherlands Organisation for Health Research and Development

Countries where clinical trial is conducted

Belgium,  Finland,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical remission without need for additional CD related therapy or surgery	Clinical remission is defined as a weighted Pediatric Crohn's Disease Activity Index (wPCDAI) score of less than 12.5 points	52 weeks
Secondary	Clinical response rates	Response is defined by a decrease in wPCDAI score above 17.5 points compared to baseline	10 weeks
Secondary	Clinical remission rates	Remission is wPCDAI<12.5	10 and 52 weeks
Secondary	Mucosal healing	Assessed by endoscopy (SES-CD) and/or fecal calprotectin (<100microgram/gram)	10 and 52 weeks
Secondary	Change in height Z-scores		10 and 52 weeks
Secondary	Change in BMI Z-scores		10 and 52 weeks
Secondary	Change bone age		10 and 52 weeks
Secondary	Change in Tanner stage		10 and 52 weeks
Secondary	Therapy failure rates over time	Therapy failure: primary non-response, loss of response according to wPCDAI and medication intolerance	52 weeks
Secondary	Adverse events rates	Adverse events includes therapy side effects, disease complications (fistulas, abscesses, strictures, surgery, extra-intestinal manifestations)	52 weeks, and 260 weeks
Secondary	Cumulative therapy use		52 weeks, and 260 weeks
Secondary	Long-term yearly remission rates without need for additional CD related therapy or surgery	Clinical remission is defined as a weighted Pediatric Crohn's Disease Activity Index (wPCDAI) score of less than 12.5 points	260 weeks
Secondary	Long-term yearly number of flares		260 weeks
Secondary	Long-term yearly clinical remission rates	Clinical remission is defined as a weighted Pediatric Crohn's Disease Activity Index (wPCDAI) score of less than 12.5 points	260 weeks
Secondary	Long-term yearly mucosal healing (calprotectin) rates	fecal calprotectin <100microgram/gram	260 weeks