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Infliximab Top-down in Pediatric Crohn (ITSKids)

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ClinicalTrials.gov Identifier: NCT01880307
Recruitment Status : Terminated (Not enough study subjects)
First Posted : June 18, 2013
Last Update Posted : July 2, 2015
Sponsor:
Collaborators:
University of Roma La Sapienza
Universitair Ziekenhuis Brussel
Information provided by (Responsible Party):
Lissy de Ridder, Erasmus Medical Center

Brief 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.

Condition or disease Intervention/treatment Phase
Crohn's Disease Drug: Azathioprine Drug: Infliximab Drug: Prednisolon Phase 4

Detailed 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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Infliximab Top-down Study in Kids With Crohn's Disease
Study Start Date : January 2013
Actual Primary Completion Date : December 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease

Arm Intervention/treatment
Experimental: 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.
Drug: Azathioprine
Other Name: Imuran

Drug: Infliximab
Other Name: Remicade

Active Comparator: Step-up
Prednisolon and azathioprine; Patients will receive induction treatment with oral prednisolone 1 mg/kg (maximum 40 mg) once daily for 4 weeks, then tapering of prednisolone in 6 weeks until stop, and receive oral azathioprine 2-3 mg/kg, once daily as maintenance treatment.
Drug: Azathioprine
Other Name: Imuran

Drug: Prednisolon



Primary Outcome Measures :
  1. Clinical remission without need for additional CD related therapy or surgery [ Time Frame: 52 weeks ]
    Clinical remission is defined as a Pediatric Crohn's Disease Activity Index (wPCDAI) score of less than 10 points


Secondary Outcome Measures :
  1. Clinical response and remission rate [ Time Frame: 10 weeks ]
    Response is defined by a decrease in PCDAI score above 15 points compared to baseline. Remission is PCDAI<10

  2. Mucosal healing [ Time Frame: 10 and 52 weeks ]
    Assessed by endoscopy (SES-CD) and/or fecal calprotectin (<100microgram/gram)

  3. Growth [ Time Frame: 10 and 52 weeks ]
    Change in height and BMI Z-scores, bone age and pubertal development

  4. Therapy failure rates over time [ Time Frame: 52 weeks ]
    Therapy failure: primary non-response, loss of response according to wPCDAI and medication intolerance

  5. Cumulative therapy use [ Time Frame: 52 weeks ]
  6. Adverse events rates [ Time Frame: 52 weeks ]
    Adverse events includes therapy side effects, disease complications (fistulas, abscesses, strictures, surgery, extra-intestinal manifestations)

  7. Long-term yearly remission rates without need for additional CD related therapy or surgery [ Time Frame: 260 weeks ]
  8. Long-term yearly clinical remission, response and mucosal healing (calprotectin) rates [ Time Frame: 260 weeks ]
  9. Yearly number of flares [ Time Frame: 260 weeks ]
  10. Cumulative therapy use [ Time Frame: 260 weeks ]
  11. Adverse event rates [ Time Frame: 260 weeks ]

Other Outcome Measures:
  1. Pharmacokinetic properties of infliximab [ Time Frame: 52 weeks ]
  2. Identification of predictive biomarkers of therapy response [ Time Frame: 52 weeks ]
  3. Correlation between clinical disease activity, fecal calprotectin and endoscopic disease severity [ Time Frame: 52 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01880307


Locations
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Italy
Sapienza University
Rome, Italy
Netherlands
Erasmus Medical Center
Rotterdam, Zuid-Holland, Netherlands, 3000 CA
Sponsors and Collaborators
Erasmus Medical Center
University of Roma La Sapienza
Universitair Ziekenhuis Brussel
Investigators
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Principal Investigator: Lissy Ridder, de, MD, PhD Erasmus Medical Center

Additional Information:
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Responsible Party: Lissy de Ridder, MD PhD, Pediatric gastroenterologist, Erasmus Medical Center
ClinicalTrials.gov Identifier: NCT01880307     History of Changes
Other Study ID Numbers: NL39202.078.12
2012-000645-13 ( EudraCT Number )
2014-005702-37 ( EudraCT Number )
First Posted: June 18, 2013    Key Record Dates
Last Update Posted: July 2, 2015
Last Verified: July 2015
Keywords provided by Lissy de Ridder, Erasmus Medical Center:
Crohn's disease
pediatric
infliximab
top-down
ITSKids
Additional relevant MeSH terms:
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Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Prednisolone
Methylprednisolone Acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone acetate
Azathioprine
Infliximab
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents
Dermatologic Agents
Antirheumatic Agents