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

Pediatric Crohns Disease Clinical Trial

— TOPIT  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02522169
• Other study ID #: 2014-000076-25
• Status: Not yet recruiting
• Phase: N/A
• First received: May 3, 2015
• Last updated: August 12, 2015
• Start date: September 2015
• Est. completion date: December 2016

Study information

• Verified date: August 2015
• Source: Klinikum Westbrandenburg GmbH
• Contact: Michael Radke, Prof. Dr. med.
• Phone: +49 331 241
• Email: mardke[@]klinikumwb.de
• Is FDA regulated: No
• Health authority: Ministry of Health: Germany
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 17 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Crohn Disease
• Inflammatory Bowel Diseases
• Pediatric Crohns Disease

Intervention

Drug:
• Infliximab
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Klinikum Westbrandenburg GmbH

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	12 months	No
Secondary	Secondary endpoint is the rate of adverse reactions	safety	12 months	Yes
Secondary	Costs of treatment		12 months	No
Secondary	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		12 months	No