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Dose Finding Study of Gadavist in Central Nervous System (CNS) Magnetic Resonance Imaging (MRI)

Primary Purpose

Brain Diseases, Spinal Cord Diseases

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Gadobutrol~0.03 mmol/kg BW (Gadavist, Gadovist, BAY86-4875)
Gadobutrol~0.1 mmol/kg BW (Gadavist, Gadovist, BAY86-4875)
Gadobutrol~0.3 mmol/kg BW (Gadavist, Gadovist, BAY86-4875)
OptiMARK~0.1 mmol/kg BW
Sponsored by
Bayer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Brain Diseases focused on measuring Contrast Agents

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with either known or highly suspected focal areas of disruption of the blood brain barrier (BBB) (eg, primary and secondary tumors, focal inflammatory or demyelinating disorders) and/or abnormal vascularity in the CNS, who are scheduled to undergo a routine contrast-enhanced MRI of the CNS.
  • Patients with untreated brain tumors should constitute a minimum of 50% of the study population and patients with treated brain tumors will be limited to a maximum of 20% of the study population

Exclusion Criteria:

  • Is a female patient who is pregnant or nursing.
  • Is a female of childbearing potential and did not have a negative urine pregnancy test the same day as the administration of gadobutrol or comparator treatment.
  • Has received any investigational product within 30 days prior to enrolling in this study.
  • Has been previously enrolled in this study or any other study using gadobutrol.
  • Has any contraindication to the MRI examinations.
  • Has a history of severe allergic or anaphylactoid reaction to any allergen including drugs and contrast agents.
  • Has received any contrast agent within 24 hours prior to gadobutrol contrast administration, or is scheduled to receive any contrast agent within 72 hours after the gadobutrol study.
  • Is considered to be clinically unstable or his/her clinical course during the study period is unpredictable (eg, due to previous surgery, acute renal failure).
  • Has been treated with high dose (>55 cobalt Gy equivalent) photon radiation or global radiotherapy for CNS lesions at any time before entering the study.
  • Is scheduled to receive chemotherapy or radiotherapy during the study period.
  • Is expected or scheduled to have a change in any treatment or procedure between the comparator and gadobutrol MRIs that may alter their interpretation.
  • Is scheduled or is likely to require a biopsy or surgery within the 72 hours after the gadobutrol MRI procedure, or is scheduled for or has undergone such interventions between the comparator and gadobutrol studies.
  • Has severe cardiovascular disease.
  • Has any contraindication to OptiMARK according to the package insert.
  • Has more than 30 brain lesions detected by any prior imaging examination.

Sites / Locations

  • University of California Davis Medical Center
  • University of California-San Diego Medical Center
  • Shands Jacksonville Medical Center
  • Emory University School of Medicine
  • Northwestern Memorial Hospital
  • Indiana Neuroscience Institute
  • Johns Hopkins University School of Medicine
  • Boston Medical Center
  • Washington University School of Medicine
  • Methodist Hospital
  • NYU Langone Medical Center
  • University of North Carolina
  • Hospital of the University of Pennsylvania
  • Temple University Hospital
  • University of Pittsburgh Medical Center Health System
  • Rhode Island Hospital
  • Medical University of South Carolina
  • Methodist Le Bonheur Healthcare
  • University of Washington Medical Center
  • University of Wisconsin - Madison
  • Fundacion Cientifica del Sur
  • TCba Salguero
  • Hospital da Beneficiência Portuguesa
  • Centro de Diagnostico Medico
  • Fundación Instituto de Alta tecnología médica de Antioquia
  • DIME Clinica Neurocardiovascular S.A.
  • Fundación Clínica Valle del Lili

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Gadobutrol~0.03 mmol/kg BW (Gadavist, BAY86-4875)

Gadobutrol~0.1 mmol/kg BW (Gadavist, BAY86-4875)

Gadobutrol~0.3 mmol/kg BW (Gadavist, BAY86-4875)

Arm Description

Participant received one dose of 0.03 mmol/kg BW of Gadobutrol and one dose of 0.1 mmol/kg body weight (BW) of OptiMARK. The order in which the participants received Gadobutrol and OptiMARK was randomized. Gadobutrol was administered via a power injector at a rate of 5 mL/s followed by a 20 mL 0.9% saline flush at the same rate.

Participant received one dose of 0.1 mmol/kg BW of Gadobutrol and one dose of 0.1 mmol/kg BW of OptiMARK. The order in which the participants received Gadobutrol and OptiMARK was randomized. Gadobutrol was administered via a power injector at a rate of 5 mL/s followed by a 20 mL 0.9% saline flush at the same rate.

Participant received one dose of 0.3 mmol/kg BW of Gadobutrol and one dose of 0.1 mmol/kg BW of OptiMARK. The order in which the participants received Gadobutrol and OptiMARK was randomized. Gadobutrol was administered via a power injector at a rate of 5 mL/s followed by a 20 mL 0.9% saline flush at the same rate.

Outcomes

Primary Outcome Measures

Categorical Visualization Score (CVS)
The primary visualization variables (number [no.] of lesions detected, border delineation, contrast enhancement, internal morphology) were condensed to a composite score (CVS). Each variable was considered a category; the CVS was calculated as: CVS=(No. of categories with increase over precontrast)-(No. of categories with decrease over precontrast). The possible outcomes of the CVS for a participant and each reader were in the range of - 3 to +4. The CVS was averaged across the 3 blinded readers, producing 1 mean CVS per participant. The higher the CVS, the more effective the treatment.
Difference in Number of Lesions Detected in Pre-contrast and Combined Pre-/Post-contrast MRI.
Three blinded readers evaluated the unenhanced MRI sets and the combined unenhanced/gadobutrol-enhanced MRI sets to evaluate the number of lesions, which was then averaged to produce an average reader value.
Assessment of Lesion Contrast Enhancement
The blinded readers assessed the degree of contrast enhancement for each lesion on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement, which was then averaged to produce an average reader score.
Assessment of Border Delineation
The blinded readers assessed the delineation for each lesion on a 4-point scale where 1 = none and 4 = excellent, which was then averaged to produce an average reader score.
Assessment of Internal Morphology
The blinded readers assessed the degree of information available about internal morphology and structure for each lesion on a 3-point scale where 1 = poor and 3 = good, which was then averaged to produce an average reader score.
Contrast to Noise Ratio (CNR) Between White and Gray Matter With Gadobutrol Perfusion MRI
CNR between white and gray matter in the perfusion imaging was defined as the signal intensity (SI) difference between white and gray matter divided by the standard deviation of the SI of white matter. An independent radiologist evaluated the gadobutrol-enhanced perfusion MRI for signal intensity.

Secondary Outcome Measures

Accuracy Comparison of Gadobutrol Doses - Detection of Matched Lesions: Blinded Reader 1
The percent accuracy (total number of lesions matching the comparator divided by the total number of lesions identified by gadobutrol) comparison of the 0.03 and 0.1 mmol/kg gadobutrol doses and the 0.1 and 0.3 mmol/kg gadobutrol doses using detection of all comparator-detected matched lesions was performed for blinded reader (BR) 1.
Accuracy Comparison of Gadobutrol Doses - Detection of Matched Lesions: Blinded Reader 2
The percent accuracy (total number of lesions matching the comparator divided by the total number of lesions identified by gadobutrol) comparison of the 0.03 and 0.1 mmol/kg gadobutrol doses and the 0.1 and 0.3 mmol/kg gadobutrol doses using detection of all comparator-detected matched lesions was performed for BR 2
Accuracy Comparison of Gadobutrol Doses - Detection of Matched Lesions: Blinded Reader 3
The percent accuracy (total number of lesions matching the comparator divided by the total number of lesions identified by gadobutrol) comparison of the 0.03 and 0.1 mmol/kg gadobutrol doses and the 0.1 and 0.3 mmol/kg gadobutrol doses using detection of all comparator-detected matched lesions was performed for BR 3
Accuracy Comparison of Gadobutrol Doses - Detection of Matched Enhanced Lesions: Blinded Reader 1
The percent accuracy (total number of lesions matching the comparator divided by the total number of lesions identified by gadobutrol) comparison of the 0.03 and 0.1 mmol/kg gadobutrol doses and the 0.1 and 0.3 mmol/kg gadobutrol doses using detection of all comparator-detected matched enhanced lesions was performed for BR 1
Accuracy Comparison of Gadobutrol Doses - Detection of Matched Enhanced Lesions: Blinded Reader 2
The percent accuracy (total number of lesions matching the comparator divided by the total number of lesions identified by gadobutrol) comparison of the 0.03 and 0.1 mmol/kg gadobutrol doses and the 0.1 and 0.3 mmol/kg gadobutrol doses using detection of all comparator-detected matched enhanced lesions was performed for BR 2
Accuracy Comparison of Gadobutrol Doses - Detection of Matched Enhanced Lesions: Blinded Reader 3
The percent accuracy (total number of lesions matching the comparator divided by the total number of lesions identified by gadobutrol) comparison of the 0.03 and 0.1 mmol/kg gadobutrol doses and the 0.1 and 0.3 mmol/kg gadobutrol doses using detection of all comparator-detected matched enhanced lesions was performed for BR 3
Evaluation of the Correct Diagnosis Following Gadobutrol-enhanced and Unenhanced MRI
The gadobutrol-enhanced and unenhanced MRI diagnoses of the average reader were compared to the final diagnosis.
Evaluation of the Diagnostic Confidence Based on Unenhanced MRI and Combined Unenhanced and Enhanced MRI
The diagnostic confidence, the level of certainty in a diagnosis, was determined based on the average of the blinded readers.
Evaluation of Perfusion Map Quality (Uncorrected Cerebral Blood Volume [CBV]) - Blinded Reader 1
BR 1 evaluated the visibility of the lesion(s) on the uncorrected CBV perfusion map.
Evaluation of Perfusion Map Quality (Uncorrected Cerebral Blood Volume (CBV)) - Blinded Reader 2
BR 2 evaluated the visibility of the lesion(s) on the uncorrected CBV perfusion map.
Evaluation of Perfusion Map Quality (Uncorrected Cerebral Blood Volume (CBV)) - Blinded Reader 3
BR 3 evaluated the visibility of the lesion(s) on the uncorrected CBV perfusion map.
Evaluation of Perfusion Map Quality (Corrected Cerebral Blood Volume (CBV)) - Blinded Reader 1
BR 1 evaluated the visibility of the lesion(s) on the corrected CBV perfusion map.
Evaluation of Perfusion Map Quality (Corrected Cerebral Blood Volume (CBV)) - Blinded Reader 2
BR 2 evaluated the visibility of the lesion(s) on the corrected CBV perfusion map.
Evaluation of Perfusion Map Quality (Corrected Cerebral Blood Volume (CBV)) - Blinded Reader 3
BR 3 evaluated the visibility of the lesion(s) on the corrected CBV perfusion map.
Evaluation of Perfusion Map Quality (Cerebral Blood Flow (CBF)) - Blinded Reader 1
BR 1 evaluated the visibility of the lesion(s) on the CBF perfusion map.
Evaluation of Perfusion Map Quality (Cerebral Blood Flow (CBF)) - Blinded Reader 2
BR 2 evaluated the visibility of the lesion(s) on the CBF perfusion map.
Evaluation of Perfusion Map Quality (Cerebral Blood Flow (CBF)) - Blinded Reader 3
BR 3 evaluated the visibility of the lesion(s) on the CBF perfusion map.
Evaluation of Perfusion Map Quality (Time to Peak (TTP)) - Blinded Reader 1
BR 1 evaluated the visibility of the lesion(s) on the TTP perfusion map.
Evaluation of Perfusion Map Quality (Time to Peak (TTP)) - Blinded Reader 2
BR 2 evaluated the visibility of the lesion(s) on the TTP perfusion map.
Evaluation of Perfusion Map Quality (Time to Peak (TTP)) - Blinded Reader 3
BR 3 evaluated the visibility of the lesion(s) on the TTP perfusion map.
Evaluation of Perfusion Map Quality (Mean Transit Time (MTT)) - Blinded Reader 1
BR 1 evaluated the visibility of the lesion(s) on the MTT perfusion map.
Evaluation of Perfusion Map Quality (Mean Transit Time (MTT)) - Blinded Reader 2
BR 2 evaluated the visibility of the lesion(s) on the MTT perfusion map.
Evaluation of Perfusion Map Quality (Mean Transit Time (MTT)) - Blinded Reader 3
BR 3 evaluated the visibility of the lesion(s) on the MTT perfusion map.
Evaluation of Perfusion Map Quality (Permeability Factor (PF) - Blinded Reader 1
BR 1 evaluated the visibility of the lesion(s) on the PF perfusion map.
Evaluation of Perfusion Map Quality (Permeability Factor (PF) - Blinded Reader 2
BR 2 evaluated the visibility of the lesion(s) on the PF perfusion map.
Evaluation of Perfusion Map Quality (Permeability Factor (PF)) - Blinded Reader 3
BR 3 evaluated the visibility of the lesion(s) on the PF perfusion map.
Evaluation of Perfusion Map Parameter Value (Uncorrected Cerebral Blood Volume (CBV)) - Independent Radiologist
The independent radiologist determined the uncorrected CBV for each lesion. CBV is the volume of blood in the tissue.
Evaluation of Perfusion Map Parameter Value (Corrected Cerebral Blood Volume (CBV)) - Independent Radiologist
The independent radiologist determined the corrected CBV for each lesion. CBV is the volume of blood in the tissue.
Evaluation of Perfusion Map Parameter Value (Cerebral Blood Flow (CBF)) - Independent Radiologist
The independent radiologist determined the CBF for each lesion. CBF is the volume of blood passing through tissue per unit of time.
Evaluation of Perfusion Map Parameter Value (Time to Peak (TTP)) - Independent Radiologist
The independent radiologist determined the TTP for each lesion. TTP is the delay between the arrival of the contrast agent bolus arrival time and the peak of the concentration curve.
Evaluation of Perfusion Map Parameter Value (Mean Transit Time (MTT)) - Independent Radiologist
The independent radiologist determined the MTT for each lesion. The MTT is the time (seconds) for contrast to pass through tissues.
Evaluation of Perfusion Map Parameter Value (Permeability Factor (PF)) - Independent Radiologist
The independent radiologist determined the PF for each lesion
Evaluation of Perfusion Map Artifacts (Uncorrected Cerebral Blood Volume (CBV)) - Blinded Reader
The blinded reader evaluated if artifacts were present on the uncorrected CBV perfusion map and recorded the type of the major artifact. EPI: echo-planar imaging; T2: transversal relaxation time.
Evaluation of Perfusion Map Artifacts (Corrected Cerebral Blood Volume (CBV)) - Blinded Reader
The blinded reader evaluated if artifacts were present on the corrected CBV perfusion map and recorded the type of the major artifact. EPI: echo-planar imaging; T2: transversal relaxation time. CBV is the fraction of the tissue volume occupied by the blood.
Evaluation of Perfusion Map Artifacts (Cerebral Blood Flow (CBF)) - Blinded Reader
The blinded reader evaluated if artifacts were present on the CBF perfusion map and recorded the type of the major artifact. EPI: echo-planar imaging; T2: transversal relaxation time
Evaluation of Perfusion Map Artifacts (Time to Peak (TTP)) - Blinded Reader
The blinded reader evaluated if artifacts were present on the TTP perfusion map and recorded the type of the major artifact. EPI: echo-planar imaging; T2: transversal relaxation time
Evaluation of Perfusion Map Artifacts (Mean Transit Time (MTT)) - Blinded Reader
The blinded reader evaluated if artifacts were present on the MTT perfusion map and recorded the type of the major artifact. EPI: echo-planar imaging; T2: transversal relaxation time
Evaluation of Perfusion Map Artifacts (Permeability Factor (PF)) - Blinded Reader
The blinded reader evaluated if artifacts were present on the PF perfusion map and recorded the type of the major artifact. EPI: echo-planar imaging; T2: transversal relaxation time
Evaluation of MRI Tumor Grade Agreement With Biopsy Results by Dose Group
The blinded readers gave an estimation of the tumor grade of brain tumors (low grade [I or II] or high grade [III or IV]) in terms of malignancy using the information obtained by perfusion imaging, which was compared to the biopsy sample results
Contrast to Noise Ratio (CNR) of Lesion/Gray Matter and Lesion/White Matter
CNR between lesion/gray matter and lesion/white matter in the perfusion imaging was defined as the signal intensity (SI) difference between lesion and gray or white matter divided by the standard deviation of background noise. An independent radiologist evaluated the gadobutrol-enhanced perfusion MRI for signal intensity.

Full Information

First Posted
November 26, 2008
Last Updated
December 11, 2013
Sponsor
Bayer
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1. Study Identification

Unique Protocol Identification Number
NCT00862459
Brief Title
Dose Finding Study of Gadavist in Central Nervous System (CNS) Magnetic Resonance Imaging (MRI)
Official Title
Multi-center, Double-blind, Randomized, Controlled, Parallel Group, Dose Comparison Study With Corresponding Blinded Image Evaluation Following a Single Intravenous Injection of Three Different Doses of Gadobutrol 1.0 Molar (Gadavist) in Patients With Known or Suspected Focal Blood Brain Barrier Disturbances and/or Abnormal Vascularity of the Central Nervous System
Study Type
Interventional

2. Study Status

Record Verification Date
December 2013
Overall Recruitment Status
Completed
Study Start Date
August 2005 (undefined)
Primary Completion Date
March 2007 (Actual)
Study Completion Date
March 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to look at the safety (what are the side effects) and efficacy (how well does it work) of Gadavist when used for taking images of the brain and spine. The results of the MRI with Gadavist Injection will be compared to the results of MR images taken without contrast and with the results of the MR images taken with OptiMARK.
Detailed Description
Safety issues are addressed in the Adverse Events section

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Diseases, Spinal Cord Diseases
Keywords
Contrast Agents

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
237 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Gadobutrol~0.03 mmol/kg BW (Gadavist, BAY86-4875)
Arm Type
Experimental
Arm Description
Participant received one dose of 0.03 mmol/kg BW of Gadobutrol and one dose of 0.1 mmol/kg body weight (BW) of OptiMARK. The order in which the participants received Gadobutrol and OptiMARK was randomized. Gadobutrol was administered via a power injector at a rate of 5 mL/s followed by a 20 mL 0.9% saline flush at the same rate.
Arm Title
Gadobutrol~0.1 mmol/kg BW (Gadavist, BAY86-4875)
Arm Type
Experimental
Arm Description
Participant received one dose of 0.1 mmol/kg BW of Gadobutrol and one dose of 0.1 mmol/kg BW of OptiMARK. The order in which the participants received Gadobutrol and OptiMARK was randomized. Gadobutrol was administered via a power injector at a rate of 5 mL/s followed by a 20 mL 0.9% saline flush at the same rate.
Arm Title
Gadobutrol~0.3 mmol/kg BW (Gadavist, BAY86-4875)
Arm Type
Experimental
Arm Description
Participant received one dose of 0.3 mmol/kg BW of Gadobutrol and one dose of 0.1 mmol/kg BW of OptiMARK. The order in which the participants received Gadobutrol and OptiMARK was randomized. Gadobutrol was administered via a power injector at a rate of 5 mL/s followed by a 20 mL 0.9% saline flush at the same rate.
Intervention Type
Drug
Intervention Name(s)
Gadobutrol~0.03 mmol/kg BW (Gadavist, Gadovist, BAY86-4875)
Intervention Description
Participant received one dose of 0.03 mmol/kg BW of Gadobutrol. Gadobutrol was administered via a power injector at a rate of 5 mL/s followed by a 20 mL 0.9% saline flush at the same rate.
Intervention Type
Drug
Intervention Name(s)
Gadobutrol~0.1 mmol/kg BW (Gadavist, Gadovist, BAY86-4875)
Intervention Description
Participant received one dose of 0.1 mmol/kg BW of Gadobutrol. Gadobutrol was administered via a power injector at a rate of 5 mL/s followed by a 20 mL 0.9% saline flush at the same rate.
Intervention Type
Drug
Intervention Name(s)
Gadobutrol~0.3 mmol/kg BW (Gadavist, Gadovist, BAY86-4875)
Intervention Description
Participant received one dose of 0.3 mmol/kg BW of Gadobutrol. Gadobutrol was administered via a power injector at a rate of 5 mL/s followed by a 20 mL 0.9% saline flush at the same rate.
Intervention Type
Drug
Intervention Name(s)
OptiMARK~0.1 mmol/kg BW
Intervention Description
Participant received one dose of 0.1 mmol/kg BW of OptiMARK. OptiMARK was administered via a power injector at a rate of 2 mL/s followed by a 20 mL 0.9% saline flush at the same rate.
Primary Outcome Measure Information:
Title
Categorical Visualization Score (CVS)
Description
The primary visualization variables (number [no.] of lesions detected, border delineation, contrast enhancement, internal morphology) were condensed to a composite score (CVS). Each variable was considered a category; the CVS was calculated as: CVS=(No. of categories with increase over precontrast)-(No. of categories with decrease over precontrast). The possible outcomes of the CVS for a participant and each reader were in the range of - 3 to +4. The CVS was averaged across the 3 blinded readers, producing 1 mean CVS per participant. The higher the CVS, the more effective the treatment.
Time Frame
up to 2 hours after the injection of study medication
Title
Difference in Number of Lesions Detected in Pre-contrast and Combined Pre-/Post-contrast MRI.
Description
Three blinded readers evaluated the unenhanced MRI sets and the combined unenhanced/gadobutrol-enhanced MRI sets to evaluate the number of lesions, which was then averaged to produce an average reader value.
Time Frame
up to 2 hours after the injection of study medication
Title
Assessment of Lesion Contrast Enhancement
Description
The blinded readers assessed the degree of contrast enhancement for each lesion on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement, which was then averaged to produce an average reader score.
Time Frame
up to 2 hours after the injection of study medication
Title
Assessment of Border Delineation
Description
The blinded readers assessed the delineation for each lesion on a 4-point scale where 1 = none and 4 = excellent, which was then averaged to produce an average reader score.
Time Frame
up to 2 hours after the injection of study medication
Title
Assessment of Internal Morphology
Description
The blinded readers assessed the degree of information available about internal morphology and structure for each lesion on a 3-point scale where 1 = poor and 3 = good, which was then averaged to produce an average reader score.
Time Frame
up to 2 hours after the injection of study medication
Title
Contrast to Noise Ratio (CNR) Between White and Gray Matter With Gadobutrol Perfusion MRI
Description
CNR between white and gray matter in the perfusion imaging was defined as the signal intensity (SI) difference between white and gray matter divided by the standard deviation of the SI of white matter. An independent radiologist evaluated the gadobutrol-enhanced perfusion MRI for signal intensity.
Time Frame
up to 2 hours after the injection of study medication
Secondary Outcome Measure Information:
Title
Accuracy Comparison of Gadobutrol Doses - Detection of Matched Lesions: Blinded Reader 1
Description
The percent accuracy (total number of lesions matching the comparator divided by the total number of lesions identified by gadobutrol) comparison of the 0.03 and 0.1 mmol/kg gadobutrol doses and the 0.1 and 0.3 mmol/kg gadobutrol doses using detection of all comparator-detected matched lesions was performed for blinded reader (BR) 1.
Time Frame
up to 2 hours after the injection of study medication
Title
Accuracy Comparison of Gadobutrol Doses - Detection of Matched Lesions: Blinded Reader 2
Description
The percent accuracy (total number of lesions matching the comparator divided by the total number of lesions identified by gadobutrol) comparison of the 0.03 and 0.1 mmol/kg gadobutrol doses and the 0.1 and 0.3 mmol/kg gadobutrol doses using detection of all comparator-detected matched lesions was performed for BR 2
Time Frame
up to 2 hours after the injection of study medication
Title
Accuracy Comparison of Gadobutrol Doses - Detection of Matched Lesions: Blinded Reader 3
Description
The percent accuracy (total number of lesions matching the comparator divided by the total number of lesions identified by gadobutrol) comparison of the 0.03 and 0.1 mmol/kg gadobutrol doses and the 0.1 and 0.3 mmol/kg gadobutrol doses using detection of all comparator-detected matched lesions was performed for BR 3
Time Frame
up to 2 hours after the injection of study medication
Title
Accuracy Comparison of Gadobutrol Doses - Detection of Matched Enhanced Lesions: Blinded Reader 1
Description
The percent accuracy (total number of lesions matching the comparator divided by the total number of lesions identified by gadobutrol) comparison of the 0.03 and 0.1 mmol/kg gadobutrol doses and the 0.1 and 0.3 mmol/kg gadobutrol doses using detection of all comparator-detected matched enhanced lesions was performed for BR 1
Time Frame
up to 2 hours after the injection of study medication
Title
Accuracy Comparison of Gadobutrol Doses - Detection of Matched Enhanced Lesions: Blinded Reader 2
Description
The percent accuracy (total number of lesions matching the comparator divided by the total number of lesions identified by gadobutrol) comparison of the 0.03 and 0.1 mmol/kg gadobutrol doses and the 0.1 and 0.3 mmol/kg gadobutrol doses using detection of all comparator-detected matched enhanced lesions was performed for BR 2
Time Frame
up to 2 hours after the injection of study medication
Title
Accuracy Comparison of Gadobutrol Doses - Detection of Matched Enhanced Lesions: Blinded Reader 3
Description
The percent accuracy (total number of lesions matching the comparator divided by the total number of lesions identified by gadobutrol) comparison of the 0.03 and 0.1 mmol/kg gadobutrol doses and the 0.1 and 0.3 mmol/kg gadobutrol doses using detection of all comparator-detected matched enhanced lesions was performed for BR 3
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of the Correct Diagnosis Following Gadobutrol-enhanced and Unenhanced MRI
Description
The gadobutrol-enhanced and unenhanced MRI diagnoses of the average reader were compared to the final diagnosis.
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of the Diagnostic Confidence Based on Unenhanced MRI and Combined Unenhanced and Enhanced MRI
Description
The diagnostic confidence, the level of certainty in a diagnosis, was determined based on the average of the blinded readers.
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of Perfusion Map Quality (Uncorrected Cerebral Blood Volume [CBV]) - Blinded Reader 1
Description
BR 1 evaluated the visibility of the lesion(s) on the uncorrected CBV perfusion map.
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of Perfusion Map Quality (Uncorrected Cerebral Blood Volume (CBV)) - Blinded Reader 2
Description
BR 2 evaluated the visibility of the lesion(s) on the uncorrected CBV perfusion map.
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of Perfusion Map Quality (Uncorrected Cerebral Blood Volume (CBV)) - Blinded Reader 3
Description
BR 3 evaluated the visibility of the lesion(s) on the uncorrected CBV perfusion map.
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of Perfusion Map Quality (Corrected Cerebral Blood Volume (CBV)) - Blinded Reader 1
Description
BR 1 evaluated the visibility of the lesion(s) on the corrected CBV perfusion map.
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of Perfusion Map Quality (Corrected Cerebral Blood Volume (CBV)) - Blinded Reader 2
Description
BR 2 evaluated the visibility of the lesion(s) on the corrected CBV perfusion map.
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of Perfusion Map Quality (Corrected Cerebral Blood Volume (CBV)) - Blinded Reader 3
Description
BR 3 evaluated the visibility of the lesion(s) on the corrected CBV perfusion map.
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of Perfusion Map Quality (Cerebral Blood Flow (CBF)) - Blinded Reader 1
Description
BR 1 evaluated the visibility of the lesion(s) on the CBF perfusion map.
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of Perfusion Map Quality (Cerebral Blood Flow (CBF)) - Blinded Reader 2
Description
BR 2 evaluated the visibility of the lesion(s) on the CBF perfusion map.
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of Perfusion Map Quality (Cerebral Blood Flow (CBF)) - Blinded Reader 3
Description
BR 3 evaluated the visibility of the lesion(s) on the CBF perfusion map.
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of Perfusion Map Quality (Time to Peak (TTP)) - Blinded Reader 1
Description
BR 1 evaluated the visibility of the lesion(s) on the TTP perfusion map.
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of Perfusion Map Quality (Time to Peak (TTP)) - Blinded Reader 2
Description
BR 2 evaluated the visibility of the lesion(s) on the TTP perfusion map.
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of Perfusion Map Quality (Time to Peak (TTP)) - Blinded Reader 3
Description
BR 3 evaluated the visibility of the lesion(s) on the TTP perfusion map.
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of Perfusion Map Quality (Mean Transit Time (MTT)) - Blinded Reader 1
Description
BR 1 evaluated the visibility of the lesion(s) on the MTT perfusion map.
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of Perfusion Map Quality (Mean Transit Time (MTT)) - Blinded Reader 2
Description
BR 2 evaluated the visibility of the lesion(s) on the MTT perfusion map.
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of Perfusion Map Quality (Mean Transit Time (MTT)) - Blinded Reader 3
Description
BR 3 evaluated the visibility of the lesion(s) on the MTT perfusion map.
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of Perfusion Map Quality (Permeability Factor (PF) - Blinded Reader 1
Description
BR 1 evaluated the visibility of the lesion(s) on the PF perfusion map.
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of Perfusion Map Quality (Permeability Factor (PF) - Blinded Reader 2
Description
BR 2 evaluated the visibility of the lesion(s) on the PF perfusion map.
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of Perfusion Map Quality (Permeability Factor (PF)) - Blinded Reader 3
Description
BR 3 evaluated the visibility of the lesion(s) on the PF perfusion map.
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of Perfusion Map Parameter Value (Uncorrected Cerebral Blood Volume (CBV)) - Independent Radiologist
Description
The independent radiologist determined the uncorrected CBV for each lesion. CBV is the volume of blood in the tissue.
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of Perfusion Map Parameter Value (Corrected Cerebral Blood Volume (CBV)) - Independent Radiologist
Description
The independent radiologist determined the corrected CBV for each lesion. CBV is the volume of blood in the tissue.
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of Perfusion Map Parameter Value (Cerebral Blood Flow (CBF)) - Independent Radiologist
Description
The independent radiologist determined the CBF for each lesion. CBF is the volume of blood passing through tissue per unit of time.
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of Perfusion Map Parameter Value (Time to Peak (TTP)) - Independent Radiologist
Description
The independent radiologist determined the TTP for each lesion. TTP is the delay between the arrival of the contrast agent bolus arrival time and the peak of the concentration curve.
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of Perfusion Map Parameter Value (Mean Transit Time (MTT)) - Independent Radiologist
Description
The independent radiologist determined the MTT for each lesion. The MTT is the time (seconds) for contrast to pass through tissues.
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of Perfusion Map Parameter Value (Permeability Factor (PF)) - Independent Radiologist
Description
The independent radiologist determined the PF for each lesion
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of Perfusion Map Artifacts (Uncorrected Cerebral Blood Volume (CBV)) - Blinded Reader
Description
The blinded reader evaluated if artifacts were present on the uncorrected CBV perfusion map and recorded the type of the major artifact. EPI: echo-planar imaging; T2: transversal relaxation time.
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of Perfusion Map Artifacts (Corrected Cerebral Blood Volume (CBV)) - Blinded Reader
Description
The blinded reader evaluated if artifacts were present on the corrected CBV perfusion map and recorded the type of the major artifact. EPI: echo-planar imaging; T2: transversal relaxation time. CBV is the fraction of the tissue volume occupied by the blood.
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of Perfusion Map Artifacts (Cerebral Blood Flow (CBF)) - Blinded Reader
Description
The blinded reader evaluated if artifacts were present on the CBF perfusion map and recorded the type of the major artifact. EPI: echo-planar imaging; T2: transversal relaxation time
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of Perfusion Map Artifacts (Time to Peak (TTP)) - Blinded Reader
Description
The blinded reader evaluated if artifacts were present on the TTP perfusion map and recorded the type of the major artifact. EPI: echo-planar imaging; T2: transversal relaxation time
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of Perfusion Map Artifacts (Mean Transit Time (MTT)) - Blinded Reader
Description
The blinded reader evaluated if artifacts were present on the MTT perfusion map and recorded the type of the major artifact. EPI: echo-planar imaging; T2: transversal relaxation time
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of Perfusion Map Artifacts (Permeability Factor (PF)) - Blinded Reader
Description
The blinded reader evaluated if artifacts were present on the PF perfusion map and recorded the type of the major artifact. EPI: echo-planar imaging; T2: transversal relaxation time
Time Frame
up to 2 hours after the injection of study medication
Title
Evaluation of MRI Tumor Grade Agreement With Biopsy Results by Dose Group
Description
The blinded readers gave an estimation of the tumor grade of brain tumors (low grade [I or II] or high grade [III or IV]) in terms of malignancy using the information obtained by perfusion imaging, which was compared to the biopsy sample results
Time Frame
up to 2 hours after the injection of study medication
Title
Contrast to Noise Ratio (CNR) of Lesion/Gray Matter and Lesion/White Matter
Description
CNR between lesion/gray matter and lesion/white matter in the perfusion imaging was defined as the signal intensity (SI) difference between lesion and gray or white matter divided by the standard deviation of background noise. An independent radiologist evaluated the gadobutrol-enhanced perfusion MRI for signal intensity.
Time Frame
up to 2 hours after the injection of study medication

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with either known or highly suspected focal areas of disruption of the blood brain barrier (BBB) (eg, primary and secondary tumors, focal inflammatory or demyelinating disorders) and/or abnormal vascularity in the CNS, who are scheduled to undergo a routine contrast-enhanced MRI of the CNS. Patients with untreated brain tumors should constitute a minimum of 50% of the study population and patients with treated brain tumors will be limited to a maximum of 20% of the study population Exclusion Criteria: Is a female patient who is pregnant or nursing. Is a female of childbearing potential and did not have a negative urine pregnancy test the same day as the administration of gadobutrol or comparator treatment. Has received any investigational product within 30 days prior to enrolling in this study. Has been previously enrolled in this study or any other study using gadobutrol. Has any contraindication to the MRI examinations. Has a history of severe allergic or anaphylactoid reaction to any allergen including drugs and contrast agents. Has received any contrast agent within 24 hours prior to gadobutrol contrast administration, or is scheduled to receive any contrast agent within 72 hours after the gadobutrol study. Is considered to be clinically unstable or his/her clinical course during the study period is unpredictable (eg, due to previous surgery, acute renal failure). Has been treated with high dose (>55 cobalt Gy equivalent) photon radiation or global radiotherapy for CNS lesions at any time before entering the study. Is scheduled to receive chemotherapy or radiotherapy during the study period. Is expected or scheduled to have a change in any treatment or procedure between the comparator and gadobutrol MRIs that may alter their interpretation. Is scheduled or is likely to require a biopsy or surgery within the 72 hours after the gadobutrol MRI procedure, or is scheduled for or has undergone such interventions between the comparator and gadobutrol studies. Has severe cardiovascular disease. Has any contraindication to OptiMARK according to the package insert. Has more than 30 brain lesions detected by any prior imaging examination.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bayer Study Director
Organizational Affiliation
Bayer
Official's Role
Study Director
Facility Information:
Facility Name
University of California Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
University of California-San Diego Medical Center
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
Shands Jacksonville Medical Center
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32209
Country
United States
Facility Name
Emory University School of Medicine
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Northwestern Memorial Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Indiana Neuroscience Institute
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
Facility Name
Johns Hopkins University School of Medicine
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Boston Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Washington University School of Medicine
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Methodist Hospital
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
NYU Langone Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
University of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Hospital of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Temple University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19146
Country
United States
Facility Name
University of Pittsburgh Medical Center Health System
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Methodist Le Bonheur Healthcare
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38104
Country
United States
Facility Name
University of Washington Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
Facility Name
University of Wisconsin - Madison
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Fundacion Cientifica del Sur
City
Lornas de Zamora
State/Province
Buenos Aires
ZIP/Postal Code
B1832BQS
Country
Argentina
Facility Name
TCba Salguero
City
Buenos Aires
Country
Argentina
Facility Name
Hospital da Beneficiência Portuguesa
City
Sao Paulo
ZIP/Postal Code
01323-001
Country
Brazil
Facility Name
Centro de Diagnostico Medico
City
Medellín
State/Province
Antioquia
Country
Colombia
Facility Name
Fundación Instituto de Alta tecnología médica de Antioquia
City
Medellín
State/Province
Antioquia
Country
Colombia
Facility Name
DIME Clinica Neurocardiovascular S.A.
City
Cali
State/Province
Valle del Cauca
Country
Colombia
Facility Name
Fundación Clínica Valle del Lili
City
Cali
Country
Colombia

12. IPD Sharing Statement

Citations:
PubMed Identifier
23681501
Citation
Breuer J, Gutierrez J, Latchaw R, Lehr R, Sorensen AG. Gadobutrol in the central nervous system at three doses: results from a phase II, randomized, multicenter trial. J Magn Reson Imaging. 2014 Feb;39(2):410-8. doi: 10.1002/jmri.24180. Epub 2013 May 16.
Results Reference
derived

Learn more about this trial

Dose Finding Study of Gadavist in Central Nervous System (CNS) Magnetic Resonance Imaging (MRI)

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