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

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ClinicalTrials.gov Identifier: NCT02517684
Recruitment Status : Active, not recruiting
First Posted : August 7, 2015
Last Update Posted : February 8, 2019
Sponsor:
Collaborators:
ZonMw: The Netherlands Organisation for Health Research and Development
Hospira, now a wholly owned subsidiary of Pfizer
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 (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.

Condition or disease Intervention/treatment Phase
Crohn's Disease Drug: Infliximab Drug: Prednisolone Other: Exclusive enteral nutrition Drug: Azathioprine Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Top-down Infliximab Study in Kids With Crohn's Disease
Actual Study Start Date : April 2015
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2023

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: Infliximab
Other Name: Inflectra

Drug: Azathioprine
Other Name: Imuran

Active Comparator: 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.
Drug: Prednisolone
Other: Exclusive enteral nutrition
Drug: Azathioprine
Other Name: Imuran




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 weighted Pediatric Crohn's Disease Activity Index (wPCDAI) score of less than 12.5 points


Secondary Outcome Measures :
  1. Clinical response rates [ Time Frame: 10 weeks ]
    Response is defined by a decrease in wPCDAI score above 17.5 points compared to baseline

  2. Clinical remission rates [ Time Frame: 10 and 52 weeks ]
    Remission is wPCDAI<12.5

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

  4. Change in height Z-scores [ Time Frame: 10 and 52 weeks ]
  5. Change in BMI Z-scores [ Time Frame: 10 and 52 weeks ]
  6. Change bone age [ Time Frame: 10 and 52 weeks ]
  7. Change in Tanner stage [ Time Frame: 10 and 52 weeks ]
  8. Therapy failure rates over time [ Time Frame: 52 weeks ]
    Therapy failure: primary non-response, loss of response according to wPCDAI and medication intolerance

  9. Adverse events rates [ Time Frame: 52 weeks, and 260 weeks ]
    Adverse events includes therapy side effects, disease complications (fistulas, abscesses, strictures, surgery, extra-intestinal manifestations)

  10. Cumulative therapy use [ Time Frame: 52 weeks, and 260 weeks ]
  11. Long-term yearly remission rates without need for additional CD related therapy or surgery [ Time Frame: 260 weeks ]
    Clinical remission is defined as a weighted Pediatric Crohn's Disease Activity Index (wPCDAI) score of less than 12.5 points

  12. Long-term yearly number of flares [ Time Frame: 260 weeks ]
  13. Long-term yearly clinical remission rates [ Time Frame: 260 weeks ]
    Clinical remission is defined as a weighted Pediatric Crohn's Disease Activity Index (wPCDAI) score of less than 12.5 points

  14. Long-term yearly mucosal healing (calprotectin) rates [ Time Frame: 260 weeks ]
    fecal calprotectin <100microgram/gram



Information from the National Library of Medicine

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

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): NCT02517684


Locations
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Belgium
University Hospital Brussels
Brussels, Belgium
University Hospitals Leuven
Leuven, Belgium
Finland
Helsinki University Central Hospital
Helsinki, Finland
Netherlands
Erasmus Medical Center
Rotterdam, Zuid-Holland, Netherlands, 3000 CA
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
Sponsors and Collaborators
Erasmus Medical Center
ZonMw: The Netherlands Organisation for Health Research and Development
Hospira, now a wholly owned subsidiary of Pfizer
Investigators
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Principal Investigator: Lissy de Ridder, MD PhD Erasmus Medical Center

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Lissy de Ridder, Pediatric Gastroenterologist, Erasmus Medical Center
ClinicalTrials.gov Identifier: NCT02517684     History of Changes
Other Study ID Numbers: NL52030.078.15
2014-005702-37 ( EudraCT Number )
MEC-2015-080 ( Other Identifier: Medical Ethical Trial Committee Erasmus MC )
First Posted: August 7, 2015    Key Record Dates
Last Update Posted: February 8, 2019
Last Verified: February 2019
Keywords provided by Lissy de Ridder, Erasmus Medical Center:
Crohn's disease
pediatric
infliximab
top-down
TISKids
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