Crohn's DiseasePhase 4ITSKidsNCT01880307
Infliximab Top-down in Pediatric Crohn
A Phase 4 study testing Azathioprine, Infliximab and Prednisolon in people with Crohn's Disease, run by Erasmus Medical Center at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 to 17 years
- Conditions the study is for
- Crohn's Disease
- What is being tested?
- Azathioprine, Infliximab and Prednisolon
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Jan 2013to Dec 2014
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
Netherlands1 site
Erasmus Medical Center
Rotterdam, South Holland, 3000 CA
About this study
Official title: Infliximab Top-down Study in Kids With Crohn's Disease
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.
Read the 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.
- Conditions
- Crohn's Disease
- Being tested
- Azathioprine, Infliximab, Prednisolon
- Keywords
- Crohn's disease, pediatric, infliximab, top-down, ITSKids
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzathioprineDrug
Also called Imuran
InfliximabDrug
Also called Remicade
PrednisolonDrug
| Study group | Role | What they receive |
|---|---|---|
| Top-down | Experimental | 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. Receives: Drug: Azathioprine; Drug: Infliximab |
| Step-up | Active comparator | 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. Receives: Drug: Azathioprine; Drug: Prednisolon |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 52 weeks
Secondary outcomes (11)
Clinical response and remission rate
Response is defined by a decrease in PCDAI score above 15 points compared to baseline. Remission is PCDAI<10
Measured: 10 weeks
Mucosal healing
Assessed by endoscopy (SES-CD) and/or fecal calprotectin (<100microgram/gram)
Measured: 10 and 52 weeks
Growth
Change in height and BMI Z-scores, bone age and pubertal development
Measured: 10 and 52 weeks
Therapy failure rates over time
Therapy failure: primary non-response, loss of response according to wPCDAI and medication intolerance
Measured: 52 weeks
Cumulative therapy use
Measured: 52 weeks
Adverse events rates
Adverse events includes therapy side effects, disease complications (fistulas, abscesses, strictures, surgery, extra-intestinal manifestations)
Measured: 52 weeks
Long-term yearly remission rates without need for additional CD related therapy or surgery
Measured: 260 weeks
Long-term yearly clinical remission, response and mucosal healing (calprotectin) rates
Measured: 260 weeks
Yearly number of flares
Measured: 260 weeks
Cumulative therapy use
Measured: 260 weeks
Adverse event rates
Measured: 260 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2013 (estimated)
- Study startJan 2013
- Primary completionDec 2014
Why it stopped: Not enough study subjects
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Crohn's DiseaseStudies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lissy de Ridder, Erasmus Medical Center
- Investigators
- Lissy Ridder, de, MD, PhD, Principal investigator, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01880307
- Sponsor's protocol ID
- NL39202.078.12
- Other IDs
- 2012-000645-13, 2014-005702-37, 2014
- Acronym
- ITSKids
- Status last verified
- Jul 2015
- First submitted
- 7 Jun 2013
- Last updated
- 2 Jul 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Infliximab Top-down Study in Kids With Crohn's Disease
- ClinicalTrials.gov ID
- NCT01880307
- Acronym / sponsor ID
- ITSKids / NL39202.078.12
- Conditions
- Crohn's Disease
- Keywords
- Crohn's disease, pediatric, infliximab, top-down, ITSKids
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Not enough study subjects
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Collaborators
- University of Roma La Sapienza, Universitair Ziekenhuis Brussel
- Study start
- Jan 2013
- Primary completion
- Dec 2014 (actual)
- First posted
- 18 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Top-down | Experimental | Drug: Azathioprine, Drug: InfliximabInfliximab 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. |
| Step-up | Active comparator | Drug: Azathioprine, Drug: PrednisolonPrednisolon 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. |
Who may qualify
- Ages
- 3 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AzathioprineAlso: Imuran | Drug | Step-up, Top-down |
| InfliximabAlso: Remicade | Drug | Top-down |
| Prednisolon | Drug | Step-up |
Primary outcome
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
11 secondary outcomes
Clinical response and remission rate
Time frame: 10 weeks
Mucosal healing
Time frame: 10 and 52 weeks
Growth
Time frame: 10 and 52 weeks
Therapy failure rates over time
Time frame: 52 weeks
Cumulative therapy use
Time frame: 52 weeks
Adverse events rates
Time frame: 52 weeks
Long-term yearly remission rates without need for additional CD related therapy or surgery
Time frame: 260 weeks
Long-term yearly clinical remission, response and mucosal healing (calprotectin) rates
Time frame: 260 weeks
Yearly number of flares
Time frame: 260 weeks
Cumulative therapy use
Time frame: 260 weeks
Adverse event rates
Time frame: 260 weeks
Results and safety
The study was stopped early (reason given: Not enough study subjects). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2015.
- Summary on Medicines for Children Research NetworkLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lissy Ridder, de, MD, PhD principal investigator
Erasmus Medical Center
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Azathioprine, Infliximab and Prednisolon in people with Crohn's Disease, run by Erasmus Medical Center at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Not enough study subjects). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical remission without need for additional CD related therapy or surgery (time frame: 52 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2015.