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

NCT ID: NCT02517684

Last Updated: 2024-03-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2024-01-31

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.

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.

Conditions

Crohn's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Infliximab

Intervention Type: DRUG

Azathioprine

Intervention Type: DRUG

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.

Group Type: ACTIVE_COMPARATOR

Prednisolone

Intervention Type: DRUG

Exclusive enteral nutrition

Intervention Type: OTHER

Azathioprine

Intervention Type: DRUG

Interventions

Infliximab

Intervention Type: DRUG

Prednisolone

Intervention Type: DRUG

Exclusive enteral nutrition

Intervention Type: OTHER

Azathioprine

Intervention Type: DRUG

Other Intervention Names

Inflectra; Imuran

Eligibility 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

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ZonMw: The Netherlands Organisation for Health Research and Development

OTHER

Sponsor Role: collaborator

Hospira, now a wholly owned subsidiary of Pfizer

INDUSTRY

Sponsor Role: collaborator

Erasmus Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Lissy de Ridder

Pediatric Gastroenterologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lissy de Ridder, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Erasmus Medical Center

Locations

University Hospital Brussels

Brussels, , Belgium

University Hospitals Leuven

Leuven, , Belgium

Helsinki University Central Hospital

Helsinki, , Finland

Erasmus Medical Center

Rotterdam, South Holland, 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

Maasstad Hospital

Rotterdam, , Netherlands

University Medical Center Utrecht

Utrecht, , Netherlands

Isala hospital

Zwolle, , Netherlands

Countries

Belgium; Finland; Netherlands

References

Vuijk SA, Jongsma MME, Hoeven BM, Cozijnsen MA, van Pieterson M, de Meij TGJ, Norbruis OF, Groeneweg M, Wolters VM, van Wering H, Hummel T, Stapelbroek J, van der Feen C, van Rheenen PF, van Wijk MP, Teklenburg S, Rizopoulos D, Poley MJ, Escher JC, de Ridder L. Randomised clinical trial: First-line infliximab biosimilar is cost-effective compared to conventional treatment in paediatric Crohn's disease. Aliment Pharmacol Ther. 2024 Jun;59(12):1510-1520. doi: 10.1111/apt.18000. Epub 2024 Apr 21.

Reference Type: DERIVED

PMID: 38644588 (View on PubMed)

Jongsma MME, Costes LMM, Tindemans I, Cozijnsen MA, Raatgreep RHC, van Pieterson M, Li Y, Escher JC, de Ridder L, Samsom JN. Serum Immune Profiling in Paediatric Crohn's Disease Demonstrates Stronger Immune Modulation With First-Line Infliximab Than Conventional Therapy and Pre-Treatment Profiles Predict Clinical Response to Both Treatments. J Crohns Colitis. 2023 Aug 21;17(8):1262-1277. doi: 10.1093/ecco-jcc/jjad049.

Reference Type: DERIVED

PMID: 36934327 (View on PubMed)

Jongsma MME, Aardoom MA, Cozijnsen MA, van Pieterson M, de Meij T, Groeneweg M, Norbruis OF, Wolters VM, van Wering HM, Hojsak I, Kolho KL, Hummel T, Stapelbroek J, van der Feen C, van Rheenen PF, van Wijk MP, Teklenburg-Roord STA, Schreurs MWJ, Rizopoulos D, Doukas M, Escher JC, Samsom JN, de Ridder L. First-line treatment with infliximab versus conventional treatment in children with newly diagnosed moderate-to-severe Crohn's disease: an open-label multicentre randomised controlled trial. Gut. 2022 Jan;71(1):34-42. doi: 10.1136/gutjnl-2020-322339. Epub 2020 Dec 31.

Reference Type: DERIVED

PMID: 33384335 (View on PubMed)

Cozijnsen MA, van Pieterson M, Samsom JN, Escher JC, de Ridder L. Top-down Infliximab Study in Kids with Crohn's disease (TISKids): an international multicentre randomised controlled trial. BMJ Open Gastroenterol. 2016 Dec 22;3(1):e000123. doi: 10.1136/bmjgast-2016-000123. eCollection 2016.

Reference Type: DERIVED

PMID: 28090335 (View on PubMed)

Other Identifiers

2014-005702-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MEC-2015-080

Identifier Type: OTHER

Identifier Source: secondary_id

NL52030.078.15

Identifier Type: -

Identifier Source: org_study_id