Pediatric Crohns DiseaseTOPITNCT02522169
TOPIT; Trough Level Optimized Pediatric Inflammatory Bowel Disease Therapy: A Multicenter Study Comparing Effectiveness of Trough Level Optimized Infliximab Maintenance Therapy With Standard Dosing Regimen of Pediatric Patients With Crohn's Disease
A study testing Infliximab in people with Pediatric Crohns Disease, run by Klinikum Westbrandenburg GmbH.
Trial summary
This clinical trail intends to evaluate interventions based on the Infliximab trough levels for an individualized therapy adaption for pediatric IBD-patients undergoing anti-TNF-alpha-therapy. Read more about this study
- Who is it for?
- Ages 6 to 17 years
- Conditions the study is for
- Pediatric Crohns Disease
- What is being tested?
- Infliximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- No sites listed yet
- Study dates
- Sep 2015to Dec 2016
- Phase
- Interventional
- 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 6 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Pediatric patients of both sexes with Cohn's disease
- Assured diagnosis of Cohn's disease according to the Porto criteria
- Regular attendance of gastroenteric consultations at one of the study centers
- Minimum patients age of 6 years, maximum age of 16 years
- Infliximab therapy with permitted / without co- medication
- Completed induction with Infliximab in accordance to the approved conventional scheme with primary therapy response
- Written consent of the patient and the legal guardian
Who cannot join
- No consent of the patient and / or legal guardian
- Serious side effects under Infliximab therapy in the past
- Primary non-responder to Infliximab after first three cycles
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Verbessertes Therapiemanagement für pädiatrische CED-Patienten Mit Chronisch-entzündlicher Darmerkrankung: Eine Randomisierte Multizentrische Studie, Welche Die Effektivität Einer Talspiegel-gesteuerten Infliximab-Erhaltungsphase Mit Dem herkömmlichen Dosierungsregime Vergleicht Trough Level Optimized Pediatric Inflammatory Bowel Disease Therapy: A Randomized Multicenter Study Comparing Effectiveness of Trough Level Optimized Infliximab Maintenance Therapy With Standard Dosing Regimen of Pediatric Patients With Crohn's Disease
This clinical trail intends to evaluate interventions based on the Infliximab trough levels for an individualized therapy adaption for pediatric IBD-patients undergoing anti-TNF-alpha-therapy. Main aim of the individualized strategy is to attain and maintain early disease control in order to keep as many patients as possible in disease remission, and to avoid primary and secondary therapy failure.
Read the detailed description
Anti TNF-alpha agents such as Infliximab are efficient and safe in treating pediatric IBD-patients. However maintaining the remission and therapeutic response is still a challenge for the practitioner. In addition to a relevant number of primary non-responding patients individual clearance and immunogenic effects lead to secondary loss of response in a significant number of patients. So far these patients are clinically managed by decrease of the infusion interval or increasing the dose. Besides an increased risk for potential side effect a high number of patients need to switch treatment to other biologicals despite interventions. Improved strategies are needed to avoid primary and secondary therapeutic failure, and a promising lead seems to be the individualized therapy.
Especially in pediatric IDB-patients with faster turnover of anti-TNF based on a higher metabolism rate new ways of adapting the dose and maintaining therapeutic serum levels are necessary. In this context the role of IFX-trough levels is not fully clear. Previous studies have shown that serum IFX trough levels correlate inversely with the turnover rate and directly to therapeutic response. Thus it is highly desirable to keep trough levels in therapeutic window. In adult patients recent studies have shown advantages in using IFX-trough levels for therapy optimization, leading to better disease control in short and long term. However there is until now no clear evidence that shows benefits for an IFX-target-level approach during the maintenance of therapy.
An early therapy optimization from the beginning on with rapid control of mucosal inflammation seems to set the pathway for sustained therapy response and disease remission.
We assume a clear benefit for an individualized, IFX-trough-level guided therapy optimization for pediatric IDB-patients and intend to clarify the role of Infliximab trough levels in this planned trial.
- Conditions
- Pediatric Crohns Disease
- Being tested
- Infliximab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InfliximabDrug
Also called Remicade
This is a randomized, prospective, parallel -controlled study, simple blinded and multicenter designed. Study centers are the Department of Child and Adolescent Medicine of the Ernst von Bergmann Hospital, Potsdam, and the Department of Child and Adolescent Medicine of Charité, Berlin.
We estimate a sample size of 50 patients per center. Study inclusion begins with given consent of the patient and the legal guardian. Patients will be randomized in control- and intervention group separately for Cohn's disease. An equal age and gender distribution is targeted for both control and intervention group. Sub groups will be formed depending on the time span from completed Infliximab induction to study enrollment (group A< 6month, group B < 6 month). Observation period is one year.
| Study group | Role | What they receive |
|---|---|---|
| Conventional treatment | Active comparator | The patients of the control group undergo Infliximab-maintenance according to the approved dosing scheme, initially with 5 mg/kg body weight Infliximab. Before each administration laboratory parameters will be controlled (Albumin, CrP, Calprotectin) and disease activity scores will be obtained (PCDAI / PUCAI). Infliximab trough levels will be assessed but not have any implication. In the presence of clinical signs of a disease exacerbation and after exclusion of other causes an adjustment of the dosage will follow for the next Infliximab-infusion:
A) interval shortening, or B) Dose increase to 10 mg / kg body weight. With a clinical stable course of the disease without signs of deterioration, the dosage and the eight-week interval will be maintained. Receives: Drug: Infliximab |
| Intervention Group | Experimental | Aiming to maintain the therapeutic window of Infliximab a de- or increase of the dose or infusion interval will be carried out for the following administration, provided the patient shows no signs of a clinical worsening. With good trough levels and clinically stable conditions the therapy will be continued without modification until next check-up. In the case of an eminent disease exacerbation Infliximab trough levels and the search for anti - Infliximab antibodies should guide further treatment decisions. With trough levels below the target range antibody testing should be performed. Receives: Drug: Infliximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
disease remission
The trial's primary endpoint is the disease remission of pediatric patients receiving Infliximab therapy after an observation period of twelve month. This will be done by comapring the PCDAI of both groups after 12 month and the PCDAI perfomance in the respective group during the observation period.
For monitoring the disease activity the PCDAI (Pediatric Crohn's Disease Activity Index) is deployed.
Measured: 12 months
Secondary outcomes (3)
Secondary endpoint is the rate of adverse reactions
safety
Measured: 12 months
Costs of treatment
Measured: 12 months
The number of patients with a reset of therapy due to secondary loss of response, e.g. to a differend biological therapy, is the focus of ths secondary outcome
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2015 (estimated)
- Study startSep 2015
- Primary completionDec 2016 (estimated)
- Study completionDec 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pediatric Crohns DiseaseStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Klinikum Westbrandenburg GmbH
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Matthias Augustin Gonçalves, Principal investigator, Klinikum Westbrandenburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02522169
- Sponsor's protocol ID
- 2014-000076-25
- Other IDs
- 2014
- Acronym
- TOPIT
- Status last verified
- Aug 2015
- First submitted
- 3 May 2015
- Last updated
- 13 Aug 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Verbessertes Therapiemanagement für pädiatrische CED-Patienten Mit Chronisch-entzündlicher Darmerkrankung: Eine Randomisierte Multizentrische Studie, Welche Die Effektivität Einer Talspiegel-gesteuerten Infliximab-Erhaltungsphase Mit Dem herkömmlichen Dosierungsregime Vergleicht Trough Level Optimized Pediatric Inflammatory Bowel Disease Therapy: A Randomized Multicenter Study Comparing Effectiveness of Trough Level Optimized Infliximab Maintenance Therapy With Standard Dosing Regimen of Pediatric Patients With Crohn's Disease
- ClinicalTrials.gov ID
- NCT02522169
- Acronym / sponsor ID
- TOPIT / 2014-000076-25
- Conditions
- Pediatric Crohns Disease
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Klinikum Westbrandenburg GmbHUniversity, hospital or other
- Study start
- Sep 2015
- Primary completion
- Dec 2016 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 13 Aug 2015 (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.
This clinical trail intends to evaluate interventions based on the Infliximab trough levels for an individualized therapy adaption for pediatric IBD-patients undergoing anti-TNF-alpha-therapy. Main aim of the individualized strategy is to attain and maintain early disease control in order to keep as many patients as possible in disease remission, and to avoid primary and secondary therapy failure.
Detailed description
Anti TNF-alpha agents such as Infliximab are efficient and safe in treating pediatric IBD-patients. However maintaining the remission and therapeutic response is still a challenge for the practitioner. In addition to a relevant number of primary non-responding patients individual clearance and immunogenic effects lead to secondary loss of response in a significant number of patients. So far these patients are clinically managed by decrease of the infusion interval or increasing the dose. Besides an increased risk for potential side effect a high number of patients need to switch treatment to other biologicals despite interventions. Improved strategies are needed to avoid primary and secondary therapeutic failure, and a promising lead seems to be the individualized therapy.
Especially in pediatric IDB-patients with faster turnover of anti-TNF based on a higher metabolism rate new ways of adapting the dose and maintaining therapeutic serum levels are necessary. In this context the role of IFX-trough levels is not fully clear. Previous studies have shown that serum IFX trough levels correlate inversely with the turnover rate and directly to therapeutic response. Thus it is highly desirable to keep trough levels in therapeutic window. In adult patients recent studies have shown advantages in using IFX-trough levels for therapy optimization, leading to better disease control in short and long term. However there is until now no clear evidence that shows benefits for an IFX-target-level approach during the maintenance of therapy.
An early therapy optimization from the beginning on with rapid control of mucosal inflammation seems to set the pathway for sustained therapy response and disease remission.
We assume a clear benefit for an individualized, IFX-trough-level guided therapy optimization for pediatric IDB-patients and intend to clarify the role of Infliximab trough levels in this planned trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Conventional treatment | Active comparator | Drug: InfliximabThe patients of the control group undergo Infliximab-maintenance according to the approved dosing scheme, initially with 5 mg/kg body weight Infliximab. Before each administration laboratory parameters will be controlled (Albumin, CrP, Calprotectin) and disease activity scores will be obtained (PCDAI / PUCAI). Infliximab trough levels will be assessed but not have any implication. In the presence of clinical signs of a disease exacerbation and after exclusion of other causes an adjustment of the dosage will follow for the next Infliximab-infusion: A) interval shortening, or B) Dose increase to 10 mg / kg body weight. With a clinical stable course of the disease without signs of deterioration, the dosage and the eight-week interval will be maintained. |
| Intervention Group | Experimental | Drug: InfliximabAiming to maintain the therapeutic window of Infliximab a de- or increase of the dose or infusion interval will be carried out for the following administration, provided the patient shows no signs of a clinical worsening. With good trough levels and clinically stable conditions the therapy will be continued without modification until next check-up. In the case of an eminent disease exacerbation Infliximab trough levels and the search for anti - Infliximab antibodies should guide further treatment decisions. With trough levels below the target range antibody testing should be performed. |
Who may qualify
- Ages
- 6 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Pediatric patients of both sexes with Cohn's disease
- Assured diagnosis of Cohn's disease according to the Porto criteria
- Regular attendance of gastroenteric consultations at one of the study centers
- Minimum patients age of 6 years, maximum age of 16 years
- Infliximab therapy with permitted / without co- medication
Key exclusion criteria (3 listed)
- No consent of the patient and / or legal guardian
- Serious side effects under Infliximab therapy in the past
- Primary non-responder to Infliximab after first three cycles
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 |
|---|---|---|
| InfliximabAlso: RemicadeThis is a randomized, prospective, parallel -controlled study, simple blinded and multicenter designed. Study centers are the Department of Child and Adolescent Medicine of the Ernst von Bergmann Hospital, Potsdam, and the Department of Child and Adolescent Medicine of Charité, Berlin. We estimate a sample size of 50 patients per center. Study inclusion begins with given consent of the patient and the legal guardian. Patients will be randomized in control- and intervention group separately for Cohn's disease. An equal age and gender distribution is targeted for both control and intervention group. Sub groups will be formed depending on the time span from completed Infliximab induction to study enrollment (group A< 6month, group B < 6 month). Observation period is one year. | Drug | Conventional treatment, Intervention Group |
Primary outcome
disease remission
Time frame: 12 months
The trial's primary endpoint is the disease remission of pediatric patients receiving Infliximab therapy after an observation period of twelve month. This will be done by comapring the PCDAI of both groups after 12 month and the PCDAI perfomance in the respective group during the observation period. For monitoring the disease activity the PCDAI (Pediatric Crohn's Disease Activity Index) is deployed.
3 secondary outcomes
Secondary endpoint is the rate of adverse reactions
Time frame: 12 months
Costs of treatment
Time frame: 12 months
The number of patients with a reset of therapy due to secondary loss of response, e.g. to a differend biological therapy, is the focus of ths secondary outcome
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2015.
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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.
Matthias Augustin Gonçalves principal investigator
Klinikum Westbrandenburg
Questions about this trial
What is this clinical trial studying?
A study testing Infliximab in people with Pediatric Crohns Disease, run by Klinikum Westbrandenburg GmbH.
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 7 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 13 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Michael Radke, Prof. Dr. med. (+49 331 241 ext. 5901, mardke@klinikumwb.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
disease remission (time frame: 12 months). 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 13 Aug 2015.