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

Erasmus University

Status and phase: Completed; Phase 4

Conditions: Crohn's Disease

Treatments: Drug: Azathioprine; Other: Exclusive enteral nutrition; Drug: Prednisolone; Drug: Infliximab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02517684

2014-005702-37 (EudraCT Number)

MEC-2015-080 (Other Identifier)

NL52030.078.15

Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 patients

Sex: All

Ages: 3 to 17 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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100 participants in 2 patient groups

Top-down

Experimental group

Description:

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.

Treatment:

Drug: Infliximab

Drug: Azathioprine

Step-up

Active Comparator group

Description:

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.

Treatment:

Other: Exclusive enteral nutrition

Drug: Prednisolone

Drug: Azathioprine