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 (TOPIT)

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.

Study Overview

• Status: Unknown
• Conditions: Pediatric Crohns Disease
• Intervention / Treatment: Drug: Infliximab

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 Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michael Radke, Prof. Dr. med.; Phone Number: 5901 +49 331 241; Email: mardke@klinikumwb.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Conventional treatment; 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.	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.; Other Names: Remicade
Experimental: Intervention Group; 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.	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.; Other Names: Remicade

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary endpoint is the rate of adverse reactions	safety	12 months
Costs of treatment		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		12 months

Collaborators and Investigators

• Sponsor: Klinikum Westbrandenburg GmbH
• Investigators: Principal Investigator: Matthias Augustin Gonçalves, Klinikum Westbrandenburg

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Anticipated): December 1, 2016
• Study Completion (Anticipated): December 1, 2016

Study Registration Dates

• First Submitted: May 3, 2015
• First Submitted That Met QC Criteria: August 12, 2015
• First Posted (Estimate): August 13, 2015

Study Record Updates

• Last Update Posted (Estimate): August 13, 2015
• Last Update Submitted That Met QC Criteria: August 12, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Antirheumatic Agents; Gastrointestinal Agents; Dermatologic Agents; Infliximab
• Other Study ID Numbers: 2014-000076-25