Clinical trial NCT02522169: 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
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Pediatric Crohns Disease
Lead sponsor: Klinikum Westbrandenburg GmbH
Sponsor class: OTHER
First posted: 2015-08-13
Enrollment: 120
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: disease remission
timeFrame: 12 months
Secondary outcomes:
measure: Secondary endpoint is the rate of adverse reactions
timeFrame: 12 months
measure: Costs of treatment
timeFrame: 12 months
measure: 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
timeFrame: 12 months
Other outcomes:
Locations:
Study officials:
affiliation: Klinikum Westbrandenburg
name: Matthias Augustin Gonçalves
role: PRINCIPAL_INVESTIGATOR
References: