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

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.

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.

Study Overview

• Status: Completed
• Conditions: Magnetic Resonance Imaging
• Intervention / Treatment: Drug: Gadobutrol (Gadavist, Gadovist, BAY86-4875)

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 1

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria, 1090
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
• Germany
  • Bayern
    • Erlangen, Bayern, Germany, 91054
  • Nordrhein-Westfalen
    • Bonn, Nordrhein-Westfalen, Germany, 53105
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
    • Leipzig, Sachsen, Germany, 04103
  • Sachsen-Anhalt
    • Halle, Sachsen-Anhalt, Germany, 06120
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24105
    • Kiel, Schleswig-Holstein, Germany, 24103
  • Thüringen
    • Jena, Thüringen, Germany, 07740
• Sweden
  • Göteborg, Sweden, 41485
  • Stockholm, Sweden, 17176
  • Uppsala, Sweden, 75185

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Clearance Estimates of Gadobutrol by Age Group	Total body clearance of Gadobutrol in plasma in L/h after intravenous injection.	From injection of Gadobutrol up to 8 hours after injection.
Body Weight-corrected Plasma Clearance Estimates of Gadobutrol by Age Group	Total body clearance of Gadobutrol in plasma corrected for body weight (L/h/kg) after intravenous injection.	From injection up to 8 hours after Gadobutrol injection
Volume Distribution at Steady State (Vss) Estimates of Gadobutrol by Age Group	Apparent volume of distribution at steady state expressed in L after intravenous injection.	From injection up to 8 hours after Gadobutrol injection
Body Weight-corrected Volume Distribution at Steady State (Vss) Estimates of Gadobutrol by Age Group	Apparent volume of distribution at steady state corrected for body weight (L/h/kg) after intravenous injection.	From injection to 8 hours after Gadobutrol injection
Area Under the Drug Concentration-time Curve of Gadobutrol by Age Group	Area under the concentration versus time curve from zero to infinity after intravenous injection expressed in µmol*h/L.	From injection to 8 hours after Gadobutrol injection
Terminal Elimination Half Life Estimates of Gadobutrol by Age Group	Terminal elimination half-life of Gadobutrol from plasma expressed in h and derived from the terminal slope of the concentration versus time curve.	From injection to 8 hours after Gadobutrol injection
Mean Residence Time (MRT) Estimates of Gadobutrol by Age Group	Mean residence time of Gadobutrol in plasma expressed in h.	From injection to 8 hours after Gadobutrol injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urinary Excretion of Gadolinium as Percent of Administered Dose	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.	up to 6 hours after Gadobutrol injection
Number of Participants With Basic Technical Adequacy of Magnetic Resonance (MR) Images for Diagnosis by Age Group	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).	Up to 1 hour after Gadobutrol injection
Number of Participants With Overall Contrast Quality of Post Contrast Images by Age Group	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).	up to 1 hour after Gadobutrol injection
Pre-Contrast Lesions by Location and by Age Group	Number of lesions on pre-contrast images by organ location and age group.	up to 1 hour after Gadobutrol injection
Post-Contrast Lesions by Location and by Age Group	Number of lesions on post-contrast images by organ location and age group.	up to 1 hour after Gadobutrol injection
Pre-Contrast Delineation of Lesion/Vessel Border by Age Group	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).	up to 1 hour after Gadobutrol injection
Post-Contrast Delineation of Lesion/Vessel Border by Age Group	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).	up to 1 hour after Gadobutrol injection
Pre-Contrast Lesion Characterization by Age Group	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).	up to 1 hour after Gadobutrol injection
Post-Contrast Lesion Characterization by Age Group	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).	up to 1 hour after Gadobutrol injection
Degree of Contrast Enhancement in Lesion/Vessel by Age Group (Given Are Total Numbers of Lesions)	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).	up to 1 hour after Gadobutrol injection
Number of Participants With Change in Diagnostic Confidence by Age Group	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).	up to 1 hour after Gadobutrol injection

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: May 2, 2007
• First Submitted That Met QC Criteria: May 2, 2007
• First Posted (Estimate): May 3, 2007

Study Record Updates

• Last Update Posted (Estimate): July 22, 2015
• Last Update Submitted That Met QC Criteria: June 29, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: Contrast-enhanced MRI; MR angiography (MRA) Children 2-17 years
• Other Study ID Numbers: 91552; 2006-004153-22 (EudraCT Number); 310788 (Other Identifier: Company internal)