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

NCT00468819 | Completed Phase 1 Results

• 3 other identifiers: 915522006-004153-22310788
• Study Type: interventional
• Target: 140
• Locations: 4 countries
• Sites: 14

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.

Conditions

Magnetic Resonance Imaging

Keywords

Contrast-enhanced MRI; MR angiography (MRA) Children 2-17 years

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (11)

• Urinary Excretion of Gadolinium as Percent of Administered Dose

  up to 6 hours after Gadobutrol injection

• Number of Participants With Basic Technical Adequacy of Magnetic Resonance (MR) Images for Diagnosis by Age Group

  Up to 1 hour after Gadobutrol injection

• Number of Participants With Overall Contrast Quality of Post Contrast Images by Age Group

  up to 1 hour after Gadobutrol injection

• Pre-Contrast Lesions by Location and by Age Group

  up to 1 hour after Gadobutrol injection

• Post-Contrast Lesions by Location and by Age Group

  up to 1 hour after Gadobutrol injection

Study Arms (4)

Gadobutrol (Gadavist, BAY86-4875) - age 2 to 6 years

EXPERIMENTAL

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)

Gadobutrol (Gadavist, BAY86-4875) - age 7 to 11 years

EXPERIMENTAL

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)

Gadobutrol (Gadavist, BAY86-4875) - age 12 to 17 years

EXPERIMENTAL

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)

Gadobutrol (Gadavist, BAY86-4875) - age 2 to 17 years

EXPERIMENTAL

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)

Interventions

Gadobutrol (Gadavist, Gadovist, BAY86-4875) DRUG

In an open-label design, all patients will receive a total dose of 0.1 mmol/kg BW Gadovist 1.01 Days Injection

Gadobutrol (Gadavist, BAY86-4875) - age 12 to 17 years; Gadobutrol (Gadavist, BAY86-4875) - age 2 to 17 years; Gadobutrol (Gadavist, BAY86-4875) - age 2 to 6 years; Gadobutrol (Gadavist, BAY86-4875) - age 7 to 11 years

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bayer: lead

Study Sites (14)

Unknown Facility

Vienna, Vienna, 1090, Austria

Location

Unknown Facility

Edmonton, Alberta, T6G 2B7, Canada

Location

Unknown Facility

Toronto, Ontario, M5G 1X8, Canada

Location

Unknown Facility

Erlangen, Bavaria, 91054, Germany

Location

Unknown Facility

Bonn, North Rhine-Westphalia, 53105, Germany

Location

Unknown Facility

Dresden, Saxony, 01307, Germany

Location

Unknown Facility

Leipzig, Saxony, 04103, Germany

Location

Unknown Facility

Halle, Saxony-Anhalt, 06120, Germany

Location

Unknown Facility

Kiel, Schleswig-Holstein, 24103, Germany

Location

Unknown Facility

Kiel, Schleswig-Holstein, 24105, Germany

Location

Unknown Facility

Jena, Thuringia, 07740, Germany

Location

Unknown Facility

Gothenburg, 41485, Sweden

Location

Unknown Facility

Stockholm, 17176, Sweden

Location

Unknown Facility

Uppsala, 75185, Sweden

Location

Related Publications (2)

• 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.

  PMID: 19858730 RESULT

• 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.

  PMID: 22409261 RESULT

Related Links

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

MeSH Terms

Interventions

gadobutrol

Limitations and Caveats

Originally, urine was collected up to 6 hours post injection in patients \> 9 years. This was amended to patients of all age groups. As a result, urine was collected in 102 of 138 patients with gadobutrol injection (lowest rate in patients 2-6 years).

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: BAYER

clinical-trials-contact@bayerhealthcare.com

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2007
• First Posted: May 3, 2007
• Study Start: May 1, 2007
• Primary Completion: April 1, 2008
• Study Completion: April 1, 2008
• Last Updated: July 22, 2015
• Results First Posted: September 5, 2011

Record last verified: 2015-06

Locations

AU (1); SE (3); DE (8); CA (2)