A Study of Magnetic Resonance Imaging (MRI) With Gadavist in Children

This study has been completed.
Sponsor:
Information provided by:
Bayer
ClinicalTrials.gov Identifier:
NCT00468819
First received: May 2, 2007
Last updated: September 10, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Magnetic Resonance Imaging
Drug: Gadobutrol (Gadavist, Gadovist, BAY86-4875)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
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.

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Plasma Clearance Estimates of Gadobutrol by Age Group [ Time Frame: From injection of Gadobutrol up to 8 hours after injection. ] [ Designated as safety issue: No ]
    Total body clearance of Gadobutrol in plasma in L/h after intravenous injection.

  • Body Weight-corrected Plasma Clearance Estimates of Gadobutrol by Age Group [ Time Frame: From injection up to 8 hours after Gadobutrol injection ] [ Designated as safety issue: No ]
    Total body clearance of Gadobutrol in plasma corrected for body weight (L/h/kg) after intravenous injection.

  • Volume Distribution at Steady State (Vss) Estimates of Gadobutrol by Age Group [ Time Frame: From injection up to 8 hours after Gadobutrol injection ] [ Designated as safety issue: No ]
    Apparent volume of distribution at steady state expressed in L after intravenous injection.

  • Body Weight-corrected Volume Distribution at Steady State (Vss) Estimates of Gadobutrol by Age Group [ Time Frame: From injection to 8 hours after Gadobutrol injection ] [ Designated as safety issue: No ]
    Apparent volume of distribution at steady state corrected for body weight (L/h/kg) after intravenous injection.

  • Area Under the Drug Concentration-time Curve of Gadobutrol by Age Group [ Time Frame: From injection to 8 hours after Gadobutrol injection ] [ Designated as safety issue: No ]
    Area under the concentration versus time curve from zero to infinity after intravenous injection expressed in µmol*h/L.

  • Terminal Elimination Half Life Estimates of Gadobutrol by Age Group [ Time Frame: From injection to 8 hours after Gadobutrol injection ] [ Designated as safety issue: No ]
    Terminal elimination half-life of Gadobutrol from plasma expressed in h and derived from the terminal slope of the concentration versus time curve.

  • Mean Residence Time (MRT) Estimates of Gadobutrol by Age Group [ Time Frame: From injection to 8 hours after Gadobutrol injection ] [ Designated as safety issue: No ]
    Mean residence time of Gadobutrol in plasma expressed in h.


Secondary Outcome Measures:
  • Urinary Excretion of Gadolinium as Percent of Administered Dose [ Time Frame: up to 6 hours after Gadobutrol injection ] [ Designated as safety issue: Yes ]
    Amount of gadolinium* excreted into urine during the collection interval 0 - 6 h post dose expressed as % of administered dose. *A metallic rare-earth element, used as a contrast medium for magnetic resonance imaging.

  • Number of Participants With Basic Technical Adequacy of Magnetic Resonance (MR) Images for Diagnosis by Age Group [ Time Frame: Up to 1 hour after Gadobutrol injection ] [ Designated as safety issue: No ]
    In the participants the technical adequacy (evaluability) of MR images was assessed on the following 4-point scale (1=not adequate [compromised quality], 2=partially adequate [evaluation possible], 3=adequate despite artifacts, 4=adequate with excellent quality).

  • Number of Participants With Overall Contrast Quality of Post Contrast Images by Age Group [ Time Frame: up to 1 hour after Gadobutrol injection ] [ Designated as safety issue: No ]
    In the participants qualitative overall contrast quality of post contrast images was assessed on the following 6-point scale (none, poor, moderate, good, excellent, not assessable).

  • Pre-Contrast Lesions by Location and by Age Group [ Time Frame: up to 1 hour after Gadobutrol injection ] [ Designated as safety issue: No ]
    Number of lesions on pre-contrast images by organ location and age group.

  • Post-Contrast Lesions by Location and by Age Group [ Time Frame: up to 1 hour after Gadobutrol injection ] [ Designated as safety issue: No ]
    Number of lesions on post-contrast images by organ location and age group.

  • Pre-Contrast Delineation of Lesion/Vessel Border by Age Group [ Time Frame: up to 1 hour after Gadobutrol injection ] [ Designated as safety issue: No ]
    In the participants pre-contrast delineation of each lesion/vessel border was assessed on the following 5-point scale (no, moderate, good, excellent, not assessable).

  • Post-Contrast Delineation of Lesion/Vessel Border by Age Group [ Time Frame: up to 1 hour after Gadobutrol injection ] [ Designated as safety issue: No ]
    In the participants post-contrast delineation of each lesion/vessel border was assessed on the following 5-point scale (no, moderate, good, excellent, not assessable).

  • Pre-Contrast Lesion Characterization by Age Group [ Time Frame: up to 1 hour after Gadobutrol injection ] [ Designated as safety issue: No ]
    In the participants the internal morphology and structure of each pre-contrast lesion was assessed on the following 4-point scale (1=poor, 2=moderate, 3=good, 4=not applicable).

  • Post-Contrast Lesion Characterization by Age Group [ Time Frame: up to 1 hour after Gadobutrol injection ] [ Designated as safety issue: No ]
    In the participants the internal morphology and structure of each post-contrast lesion was assessed on the following 4-point scale (1=poor, 2=moderate, 3=good, 4=not applicable).

  • Degree of Contrast Enhancement in Lesion/Vessel by Age Group (Given Are Total Numbers of Lesions) [ Time Frame: up to 1 hour after Gadobutrol injection ] [ Designated as safety issue: No ]
    In the participants the degree of contrast enhancement in each lesion/vessel was assessed on the following 5-point scale (1=no, 2=moderate, 3=good, 4=excellent, 5=not applicable).

  • Number of Participants With Change in Diagnostic Confidence by Age Group [ Time Frame: up to 1 hour after Gadobutrol injection ] [ Designated as safety issue: No ]
    In the participants the change in diagnostic confidence (additional diagnostic gain by the post-contrast scan) was assessed on the following 3-point scale (1=unchanged, 2=improved, 3=worsened).


Enrollment: 140
Study Start Date: May 2007
Study Completion Date: April 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Gadobutrol (Gadavist, BAY86-4875) - age 2 to 6 years
Participants received Gadobutrol 0.1 mmol/kg body weight (BW) = 0.1 mL/kg BW as single intravenous bolus injection
Drug: Gadobutrol (Gadavist, Gadovist, BAY86-4875)
In an open-label design, all patients will receive a total dose of 0.1 mmol/kg BW Gadovist 1.01 Days Injection
Experimental: Gadobutrol (Gadavist, BAY86-4875) - age 7 to 11 years
Participants received Gadobutrol 0.1 mmol/kg body weight (BW) = 0.1 mL/kg BW as single intravenous bolus injection
Drug: Gadobutrol (Gadavist, Gadovist, BAY86-4875)
In an open-label design, all patients will receive a total dose of 0.1 mmol/kg BW Gadovist 1.01 Days Injection
Experimental: Gadobutrol (Gadavist, BAY86-4875) - age 12 to 17 years
Participants received Gadobutrol 0.1 mmol/kg body weight (BW) = 0.1 mL/kg BW as single intravenous bolus injection
Drug: Gadobutrol (Gadavist, Gadovist, BAY86-4875)
In an open-label design, all patients will receive a total dose of 0.1 mmol/kg BW Gadovist 1.01 Days Injection
Experimental: Gadobutrol (Gadavist, BAY86-4875) - age 2 to 17 years
Participants received Gadobutrol 0.1 mmol/kg body weight (BW) = 0.1 mL/kg BW as single intravenous bolus injection
Drug: Gadobutrol (Gadavist, Gadovist, BAY86-4875)
In an open-label design, all patients will receive a total dose of 0.1 mmol/kg BW Gadovist 1.01 Days Injection

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   2 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00468819

Locations
Austria
Wien, Austria, 1090
Canada, Alberta
Edmonton, Alberta, Canada, T6G 2B7
Canada, Ontario
Toronto, Ontario, Canada, M5G 1X8
Germany
Erlangen, Bayern, Germany, 91054
Bonn, Nordrhein-Westfalen, Germany, 53105
Halle, Sachsen-Anhalt, Germany, 06120
Dresden, Sachsen, Germany, 01307
Leipzig, Sachsen, Germany, 04103
Kiel, Schleswig-Holstein, Germany, 24105
Kiel, Schleswig-Holstein, Germany, 24103
Jena, Thüringen, Germany, 07740
Sweden
Göteborg, Sweden, 41485
Stockholm, Sweden, 17176
Uppsala, Sweden, 75185
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Publications:
Responsible Party: Therapeutic Area Head, Bayer HealthCare Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT00468819     History of Changes
Other Study ID Numbers: 91552, 2006-004153-22, 310788
Study First Received: May 2, 2007
Results First Received: June 10, 2011
Last Updated: September 10, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Denmark: Danish Medicines Agency
Sweden: Medical Products Agency
Austria: Agency for Health and Food Safety
Canada: Health Canada

Keywords provided by Bayer:
Contrast-enhanced MRI
MR angiography (MRA) Children 2-17 years

Additional relevant MeSH terms:
Gadobutrol
Contrast Media
Diagnostic Uses of Chemicals
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014