Gadobutrol Enhanced MRA of the Supra-aortic Vessels (GEMSAV)

• Proportion of assessable segments [ Time Frame: Up to 2 weeks ] [ Designated as safety issue: No ]
• Sensitivity for detection of clinically significant disease (70 to 99% stenosis) on a segmental basis [ Time Frame: Up to 2 weeks ] [ Designated as safety issue: No ]
• Specificity for exclusion of clinically significant disease (70 to 99% stenosis) on a segmental basis [ Time Frame: Up to 2 weeks ] [ Designated as safety issue: No ]
• Gadovist minimum performance criteria: Sensitivity > 50% [ Time Frame: Up to 2 weeks ] [ Designated as safety issue: No ]
• Gadobutrol minimum performance criteria: Specificity > 50% [ Time Frame: Up to 2 weeks ] [ Designated as safety issue: No ]

• Proportion of assessable segments [ Time Frame: At approximately 15 months after last patient, last visit ] [ Designated as safety issue: No ]
• Sensitivity for detection of clinically significant disease (70 to 99% stenosis) on a segmental basis [ Time Frame: At approximately 15 months after last patient, last visit ] [ Designated as safety issue: No ]
• Specificity for exclusion of clinically significant disease (70 to 99% stenosis) on a segmental basis [ Time Frame: At approximately 15 months after last patient, last visit ] [ Designated as safety issue: No ]
• Gadovist minimum performance criteria: Sensitivity > 50% [ Time Frame: At approximately 15 months after last patient, last visit ] [ Designated as safety issue: No ]
• Gadobutrol minimum performance criteria: Specificity > 50% [ Time Frame: At approximately 15 months after last patient, last visit ] [ Designated as safety issue: No ]

• Minimum diameter of the segment [ Time Frame: Up to 2 weeks ] [ Designated as safety issue: No ]
• Location and length of stenotic segments with ≥ 70% stenosis [ Time Frame: Up to 2 weeks ] [ Designated as safety issue: No ]
• Secondary radiologic indicators for diagnosis of clinically significant disease [ Time Frame: Up to 2 weeks ] [ Designated as safety issue: No ]
• Artifacts by type (segmental) [ Time Frame: Up to 2 weeks ] [ Designated as safety issue: No ]
• Diagnostic confidence (segmental) [ Time Frame: Up to 2 weeks ] [ Designated as safety issue: No ]
• Additional imaging studies recommended (example: CTA, CE MRA, Ultrasound, Nuclear Medicine) [ Time Frame: Up to 2 weeks ] [ Designated as safety issue: No ]
  What additional imaging studies would be necessary is a measure of 1) what test provides a definitive diagnosis for treatment decisions and 2) is a direct measure of additional cost a health system would incur for additional imaging studies to reach a definitive diagnosis. This is critical to determining the total cost of imaging for a patient diagnosis in any health system reimbursement structure. Therefore the social/societal cost for not providing a definitive diagnosis with a single imaging study can be determined for health policy and reimbursement decisions.

• Minimum diameter of the segment [ Time Frame: At approximately 15 months after last patient, last visit ] [ Designated as safety issue: No ]
• Location and length of stenotic segments with ≥ 70% stenosis [ Time Frame: At approximately 15 months after last patient, last visit ] [ Designated as safety issue: No ]
• Secondary radiologic indicators for diagnosis of clinically significant disease [ Time Frame: At approximately 15 months after last patient, last visit ] [ Designated as safety issue: No ]
• Artifacts by type (segmental) [ Time Frame: At approximately 15 months after last patient, last visit ] [ Designated as safety issue: No ]
• Diagnostic confidence (segmental) [ Time Frame: At approximately 15 months after last patient, last visit ] [ Designated as safety issue: No ]
• Additional imaging studies recommended (example: CTA, CE MRA, Ultrasound, Nuclear Medicine) [ Time Frame: At approximately 15 months after last patient, last visit ] [ Designated as safety issue: No ]

  What additional imaging studies would be necessary is a measure of 1) what test provides a definitive diagnosis for treatment decisions and 2) is a direct measure of additional cost a health system would incur for additional imaging studies to reach a definitive diagnosis. This is critical to determining the total cost of imaging for a patient diagnosis in any health system reimbursement structure.

  Therefore the social/societal cost for not providing a definitive diagnosis with a single imaging study can be determined for health policy and reimbursement decisions.

Subjects referred for a routine CTA (computed tomography angiography) or MRA (magnetic resonance angiography) will be invited to participate in the study and subjects will be involved in the study for between 2 and 12 days. Two to three visits to the study doctor will be required.

This study will compare the diagnostic results of Gadobutrol enhanced MRA images with MRA images taken without contrast agent using images from a CTA as the standard of reference, which may have been performed up to 60 days prior to enrolment. If a CTA has not been performed in this prior time period, a CTA is required for the study.

MRA and CTA images will be collected for an independent review (blinded read).

Inclusion Criteria:

• Male or female subjects, aged 18 years and older

• Any of the following:

  • Known or suspected supra-aortic arterial disease based on:

    • Prior stroke
    • Transient ischemic attack (TIA)
    • Amaurosis Fugax (transient monocular blindness)
  • Referred for evaluation of any supra-aortic vessel (for clinically significant stenosis)
  • Follow-up for a stent in a supra-aortic vessel
  • Prior imaging study (CTA or ultrasound) showing ≥ 50% stenosis of a supra-aortic vessel segment (within 60 days before consent). The proportion of subjects with positive disease (determined by the investigator, based on CTA or ultrasound) will be monitored during the study, and enrolment may be further restricted to require ≥ 70% stenosis to ensure that overall there are an adequate number of subjects with clinically significant disease for the evaluation of study endpoints.
• Willingness to undergo the routine Contrast Enhanced Magnetic Resonance Angiography [CE MRA] examination with gadobutrol
• Willingness and ability to follow directions and complete all study procedures specified in the protocol
• Females of childbearing potential only: Negative pregnancy test on the day of the MRA before the administration of study drug

Exclusion Criteria:

• Pregnant or nursing (including pumping for storage and feeding)
• Received any other investigational product or participation in any other clinical trial within 30 days before enrollment into this study
• Previous enrollment into this study or into any other Bayer sponsored study using gadobutrol
• Contraindication to the MRA examinations (e.g. inability to hold breath; severe arrhythmias; very low cardiac output, severe claustrophobia, defibrillators or other metallic devices not approved for MRI)
• Contraindication to the use of Gd-containing contrast agents (including subjects with suspicion for or known to have Nephrogenic Systemic Fibrosis [NSF])
• History of severe allergic or anaphylactoid reaction to any allergen including drugs and contrast agents
• Received any contrast agent within 72 hours before the study MRA, or scheduled receipt of any contrast agent within 24 hours after the study MRA (Note: This applies also to a CTA potentially scheduled during the course of the study.)
• Estimated glomerular filtration rate (eGFR) value < 30 ml/min/1.73 m2 derived from a serum creatinine result within 2 weeks before the gadobutrol injection. Any subject on hemodialysis or peritoneal dialysis is excluded from participation. Use the value obtained prior to and closest to the time of the MRA, if there are multiple creatinine values. (Do not use the core lab value if not available prior to the MRA.)
• Acute renal insufficiency of any intensity, either due to hepato-renal syndrome or occurring in the peri-operative liver transplantation period
• Severe cardiovascular disease (e.g. acute myocardial infarction [< 14 days], unstable angina, congestive heart failure New York Heart Association class IV) or known long QT syndrome
• Suspected clinical instability or unpredictability of the clinical course during the study period (e.g. due to previous surgery)

• Scheduled or potentially expected for the period between the CTA and gadobutrol MRA:

  • Any procedure that may alter the MRA or CTA interpretation, or
  • Any interventional or surgical procedure involving the supra-aortic vessels