Infliximab Top-down in Pediatric Crohn

Phase 4TerminatedNCT01880307

Erasmus Medical Center13 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Crohn's Disease

Interventions

AzathioprineDRUG

InfliximabDRUG

PrednisolonDRUG

Eligibility

Sex: ALLMin age: 3 YearsMax age: 17 Years

Medical Language ↔ Plain English

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.

Locations (2)

Sapienza University

Rome, Italy

Erasmus Medical Center

Rotterdam, South Holland, Netherlands

Outcomes

Primary Outcomes

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

Time frame: 52 weeks

Secondary Outcomes

Clinical response and remission rate

Response is defined by a decrease in PCDAI score above 15 points compared to baseline. Remission is PCDAI\<10

Time frame: 10 weeks

Mucosal healing

Assessed by endoscopy (SES-CD) and/or fecal calprotectin (\<100microgram/gram)

Time frame: 10 and 52 weeks

Growth

Change in height and BMI Z-scores, bone age and pubertal development

Time frame: 10 and 52 weeks

Therapy failure rates over time

Therapy failure: primary non-response, loss of response according to wPCDAI and medication intolerance

Time frame: 52 weeks

Cumulative therapy use

Time frame: 52 weeks

Adverse events rates

Adverse events includes therapy side effects, disease complications (fistulas, abscesses, strictures, surgery, extra-intestinal manifestations)

Time frame: 52 weeks

Long-term yearly remission rates without need for additional CD related therapy or surgery

Time frame: 260 weeks

Data from ClinicalTrials.gov

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