Clinical Trial: Gadobutrol Enhanced MRA of the Renal Arteries

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Multicenter, Open-label Study to Evaluate the Safety and Efficacy (by Blinded Reading) of Gadobutrol-enhanced Magnetic Resonance Angiography (MRA) After a Single Injection of 0.1 mmol/kg of Gadobutrol

Brief Summary:

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).


Detailed Summary:
Sponsor: Bayer

Current Primary Outcome:

  • Percentage of Assessable Vascular Segments Using Gadobutrol-Enhanced MRA and Unenhanced MRA [ Time Frame: Images were taken pre-injection and post-injection ]
    Each vascular segment was visualized using unenhanced MRA and gadobutrol-enhanced MRA, characterized by the on-site investigators, three independent blinded readers (reader 1, 2 and 3) and majority readers (the outcome determined by at least two of the blinded readers). The segments were predefined to standardize the blinded reader evaluations. A segment was assessable if it was visualized along its entire length and if any region of stenosis, was measured reliably. There were 6 segments assessed per participant (3 segments in the right renal artery and 3 segments in the left renal artery) and up to 9 segments in participants with renal transplant.
  • Sensitivity for Detection of Clinically Significant Disease Using Gadobutrol-Enhanced MRA and Unenhanced MRA [ Time Frame: Images were taken pre-injection and post-injection ]
    Clinically significant disease was defined as 50 to 99 percent (%) stenosis of a segment, but not occluded as assessed by the SoR. For each segment, the most severe stenosis/narrowing was identified and considered for the evaluation of clinically significant disease.
  • Specificity for Exclusion of Clinically Significant Disease Using Gadobutrol-Enhanced MRA and Unenhanced MRA [ Time Frame: Images were taken pre-injection and post-injection ]
    Clinically significant disease (stenosis) was defined as 50 to 99 percent (%) stenosis of a segment, but not occluded as assessed by the SoR. For each segment, the most severe stenosis/narrowing was identified and cons

    Original Primary Outcome:

    • Fraction of assessable segments [ Time Frame: At approximately 15 months after last patient last visit. ]
    • Sensitivity for detection of clinically significant disease (50 to 99% stenosis) on a segmental basis [ Time Frame: At approximately 15 months after last patient last visit. ]
    • Specificity for exclusion of clinically significant disease (50 to 99% stenosis) on a segmental basis [ Time Frame: At approximately 15 months after last patient last visit. ]
    • Gadovist minimum performance criteria: Sensitivity > 50% [ Time Frame: At approximately 15 months after last patient last visit. ]
    • Gadovist minimum performance criteria: Specificity > 50% [ Time Frame: At approximately 15 months after last patient last visit. ]


    Current Secondary Outcome:

    • Length of the Right and Left Renal Arteries Assessed by Gadobutrol-enhanced MRA and Unenhanced MRA - Blinded Reader [ Time Frame: Images were taken pre-injection and post-injection ]
      The length of the left and right renal arteries were measured from the origin at the aorta to the bifurcation into the upper and lower pole arteries or the most distal point of the renal artery which could be visualized. This distal margin was the point where the diameter was still assessable. If there were more than 2 distal branches then the first large branch that was the dominant supply to a renal pole was used as the distal point.
    • Length of the Right and Left Renal Arteries Assessed by Computed Tomographic Angiography (CTA) - Blinded Reader [ Time Frame: Images were taken pre-injection and post-injection ]
      The length of the left and right renal arteries were measured from the origin at the aorta to the bifurcation into the upper and lower pole arteries or the most distal point of the renal artery which could be visualized. This distal margin was the point where the diameter was still assessable. If there were more than 2 distal branches then the first large branch that was the dominant supply to a renal pole was used as the distal point.
    • Vessel Diameter (Millimeter [mm]) at the Normal Point and the Narrowest Point in Gadobutrol-Enhanced MRA, Unenhanced MRA and CTA Images [ Time Frame: Images were taken pre-injection and post-injection ]
      The segment reduction in diameter (DIA) of greater than 10% was considered abnormal and measured. The diameter of each of these abnormal segments was measured using electronic calipers (perpendicular to the long axis of the vessel) at the point of most severe stenosis within each segment. Mean of vessel diameters was calculated by segment separately for CTA and MRA readers. For the ease of expression, the following abbreviations will be used: Diameter (DIA), Blinded Reader (BR).
    • The Percentage of Location of Stenosis >= 50% (Within and Beyond 5 Millimeter From the Aorta) in the Proximal Segments Assessed by Gadobutrol-Enhanced MRA and Unenhanced MRA [ Time Frame: Images were taken pre-injection and post-injection ]
      Location within the right and left proximal segment was based on the point of greatest stenosis and was recorded for stenosis >=50% as: - Within 5 mm of the aorta (or occlusion proximal to the origin of the segment); - Beyond 5 mm from the aorta.
    • The Percentage of Segments With Artifacts Presence [ Time Frame: Images were taken pre-injection and post-injection ]
      Artifacts were collected for the MRA images on a segmental basis.
    • Types of Artifacts Assessed by Gadobutrol-enhanced MRA and Unenhanced MRA by Blinded Reader 1 [ Time Frame: Images were taken pre-injection and post-injection ]
      The following types of artifacts were considered: Motion artifact (including pulsatility, breathing, swallowing), venous opacification, saturation artifact (for example [eg], in-plane flow, turbulence, dephasing, saturation band), susceptibility artifacts (including devices, eg, stents), ringing artifact (eg, bands), bolus timing error, and other (artifact not specified above or no artifact).
    • Types of Artifacts Assessed by Gadobutrol-enhanced MRA and Unenhanced MRA by Blinded Reader 2 [ Time Frame: Images were taken pre-injection and post-injection ]
      The following types of artifacts were considered: Motion artifact (including pulsatility, breathing, swallowing), venous opacification, saturation artifact (for example [eg], in-plane flow, turbulence, dephasing, saturation band), susceptibility artifacts (including devices, eg, stents), ringing artifact (eg, bands), bolus timing error, and other (artifact not specified above or no artifact).
    • Types of Artifacts Assessed by Gadobutrol-enhanced MRA and Unenhanced MRA by Blinded Reader 3 [ Time Frame: Images were taken pre-injection and post-injection ]
      The following types of artifacts were considered: Motion artifact (including pulsatility, breathing, swallowing), venous opacification, saturation artifact (for example [eg], in-plane flow, turbulence, dephasing, saturation band), susceptibility artifacts (including devices, eg, stents), ringing artifact (eg, bands), bolus timing error, and other (artifact not specified above or no artifact).
    • The Percentage of Accessory (Non-dominant) Renal Artery Presence Assessed by Gadobutrol-Enhanced MRA and Unenhanced MRA [ Time Frame: Images were taken pre-injection and post-injection ]
      An accessory renal artery was defined as an additional, non-dominant, renal artery typically emanating from the aorta and anastomosing distal to the proximal third, segment of that renal artery. It was recorded only as present or absent on the right and left, regardless of how many accessory renal arteries were present.
    • The Presence of Any Aneurysmal Dilatation in Each Segment (Proximal, Mid- and Distal) in the Right and the Left Renal Arteries Assessed by Gadobutrol-Enhanced MRA and Unenhanced MRA [ Time Fram

      Original Secondary Outcome:

      • Minimum diameter of the segment [ Time Frame: At approximately 15 months after last patient last visit. ]
      • Location and length of stenotic segments with ≥ 50% stenosis [ Time Frame: At approximately 15 months after last patient last visit. ]
      • Aneurysmal dilatation [ Time Frame: At approximately 15 months after last patient last visit. ]
      • Artifacts by type (segmental) [ Time Frame: At approximately 15 months after last patient last visit. ]
      • Diagnostic confidence (segmental) [ Time Frame: At approximately 15 months after last patient last visit. ]
      • Additional imaging studies recommended (example: non contrast MRA, contrast enhanced MRA, computed tomography angiography, Ultrasound, Nuclear medicine study) [ Time Frame: At approximately 15 months after last patient last visit. ]

        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.



      Information By: Bayer

      Dates:
      Date Received: April 5, 2011
      Date Started: May 2011
      Date Completion:
      Last Updated: July 29, 2015
      Last Verified: July 2015