Clinical trial NCT00468819: A Study of Magnetic Resonance Imaging (MRI) With Gadavist in Children
Official title: Open-label Multi-center Study of Magnetic Resonance Imaging (MRI) With 0.1 mmol/kg Body Weight (BW) Gadavist (1.0 M) to Assess Pharmacokinetics, Safety and Tolerability in Children.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Magnetic Resonance Imaging
Keywords: Contrast-enhanced MRI
MR angiography (MRA) Children 2-17 years
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2007-05-03
Enrollment: 140
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: In this clinical study a contrast agent for magnetic resonance imaging (MRI), which has already been approved for application in adults, will be investigated in children and adolescents. MRI is a modern and safe examination method without delivering radiation burden using magnetic fields to produce cross-sectional images of the human body. A special computer program then puts these images together and creates a two or three-dimensional image of the inner organs thus facilitating the detection and evaluation of pathological changes. In contrast-enhanced MRI a contrast agent is injected into a peripheral vein before the examination which results in a stronger contrast in the examined area. Therefore, pathological changes can be more easily detected and evaluated compared to non-enhanced MRI. The company Bayer HealthCare Pharmaceuticals has developed a contrast agent for MRI called Gadavist 1.0 which was first approved in 1998 in Switzerland for MRI of brain and spine. Since 2003 Gadavist can also be used in magnetic resonance angiography (MRA) in adults, i.e. in the MRI examination of the blood vessels and since 2006 in MRI of liver and kidney disease. Gadavist was examined in more than 2,900 adults within the framework of clinical studies during development and has been used after its marketing authorization in meanwhile more than 600,000 patients. Yet, clinical studies investigating Gadavist have been only conducted with adults so far. Diseases requiring MRI examinations, however, often occur in children, too. Therefore, many contrast agents are already used on a regular basis in MRI examinations of children, some of these contrast agents being authorized already. Within the framework of this study the pharmacokinetic characteristics of Gadavist in children or adolescents will be investigated, i.e. how the contrast agent is distributed and behaves in the body. In addition, safety and tolerability will be evaluated in order to demonstrate that Gadavist 1.0 is a safe and well tolerated contrast agent also for children and adolescents. Furthermore, the study aims to obtain the dosage recommendation of 0.1 ml per kilogram body weight also for this population group.

Detailed description: Please note that the present study is allocated two study phases, i.e. phase I and phase III.

Eligibility criteria: Inclusion Criteria:

* Patients (male/ female) of specific age groups (2-6 years, 7-11 years, 12-17 years) who are scheduled to undergo Gadolinium (Gd)-enhanced MRI of brain, spine, liver and/or kidneys or Gd-enhanced MRA (single field of view).

Exclusion Criteria:

* Clinically unstable patients (e.g. intensive care unit)
* Renal insufficiency
* Patients undergoing a relevant change in chemotherapy \</= 48 hours prior to and up to 24 hours after the administration of Gadovist.

Primary outcomes:
measure: Plasma Clearance Estimates of Gadobutrol by Age Group
timeFrame: From injection of Gadobutrol up to 8 hours after injection.
measure: Body Weight-corrected Plasma Clearance Estimates of Gadobutrol by Age Group
timeFrame: From injection up to 8 hours after Gadobutrol injection
measure: Volume Distribution at Steady State (Vss) Estimates of Gadobutrol by Age Group
timeFrame: From injection up to 8 hours after Gadobutrol injection
measure: Body Weight-corrected Volume Distribution at Steady State (Vss) Estimates of Gadobutrol by Age Group
timeFrame: From injection to 8 hours after Gadobutrol injection
measure: Area Under the Drug Concentration-time Curve of Gadobutrol by Age Group
timeFrame: From injection to 8 hours after Gadobutrol injection
measure: Terminal Elimination Half Life Estimates of Gadobutrol by Age Group
timeFrame: From injection to 8 hours after Gadobutrol injection
measure: Mean Residence Time (MRT) Estimates of Gadobutrol by Age Group
timeFrame: From injection to 8 hours after Gadobutrol injection
Secondary outcomes:
measure: Urinary Excretion of Gadolinium as Percent of Administered Dose
timeFrame: up to 6 hours after Gadobutrol injection
measure: Number of Participants With Basic Technical Adequacy of Magnetic Resonance (MR) Images for Diagnosis by Age Group
timeFrame: Up to 1 hour after Gadobutrol injection
measure: Number of Participants With Overall Contrast Quality of Post Contrast Images by Age Group
timeFrame: up to 1 hour after Gadobutrol injection
measure: Pre-Contrast Lesions by Location and by Age Group
timeFrame: up to 1 hour after Gadobutrol injection
measure: Post-Contrast Lesions by Location and by Age Group
timeFrame: up to 1 hour after Gadobutrol injection
measure: Pre-Contrast Delineation of Lesion/Vessel Border by Age Group
timeFrame: up to 1 hour after Gadobutrol injection
measure: Post-Contrast Delineation of Lesion/Vessel Border by Age Group
timeFrame: up to 1 hour after Gadobutrol injection
measure: Pre-Contrast Lesion Characterization by Age Group
timeFrame: up to 1 hour after Gadobutrol injection
measure: Post-Contrast Lesion Characterization by Age Group
timeFrame: up to 1 hour after Gadobutrol injection
measure: Degree of Contrast Enhancement in Lesion/Vessel by Age Group (Given Are Total Numbers of Lesions)
timeFrame: up to 1 hour after Gadobutrol injection
measure: Number of Participants With Change in Diagnostic Confidence by Age Group
timeFrame: up to 1 hour after Gadobutrol injection
Other outcomes:
Locations:
city: Wien
country: Austria
city: Edmonton
country: Canada
state: Alberta
city: Toronto
country: Canada
state: Ontario
city: Erlangen
country: Germany
state: Bayern
city: Bonn
country: Germany
state: Nordrhein-Westfalen
city: Halle
country: Germany
state: Sachsen-Anhalt
city: Dresden
country: Germany
state: Sachsen
city: Leipzig
country: Germany
state: Sachsen
city: Kiel
country: Germany
state: Schleswig-Holstein
city: Kiel
country: Germany
state: Schleswig-Holstein
city: Jena
country: Germany
state: Thüringen
city: Göteborg
country: Sweden
city: Stockholm
country: Sweden
city: Uppsala
country: Sweden
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Hahn G, Sorge I, Gruhn B, Glutig K, Hirsch W, Bhargava R, Furtner J, Born M, Schroder C, Ahlstrom H, Kaiser S, Moritz JD, Kunze CW, Shroff M, Stokland E, Trnkova ZJ, Schultze-Mosgau M, Reif S, Bacher-Stier C, Mentzel HJ. Pharmacokinetics and safety of gadobutrol-enhanced magnetic resonance imaging in pediatric patients. Invest Radiol. 2009 Dec;44(12):776-83. doi: 10.1097/RLI.0b013e3181bfe2d2.
citation: Reif S, Schultze-Mosgau M, Sutter G. From adults to children: simulation-based choice of an appropriate sparse-sampling schedule. Paediatr Drugs. 2012 Jun 1;14(3):189-200. doi: 10.2165/11595430-000000000-00000.