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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01344447
First received: April 5, 2011
Last updated: July 29, 2015
Last verified: July 2015
  Purpose

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).


Condition Intervention Phase
Carotid Stenosis
Drug: Gadobutrol (Gadovist, BAY86-4875)
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Multicenter, Open-label Study to Evaluate the Safety and Efficacy (by Blinded Reading) of Contrast-Enhanced Magnetic Resonance Angiography (MRA) After a Single Intravenous Injection of 0.1 mmol/kg Gadobutrol in Subjects With Known or Suspected Vascular Disease of the Supra-aortic Vessels

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Percentage of Assessable Vascular Segments Using Gadobutrol-Enhanced MRA and Unenhanced MRA [ Time Frame: Images were taken pre-injection and post-injection ] [ Designated as safety issue: No ]
    Each vascular segment was visualized using unenhanced MRA and gadobutrol-enhanced MRA, characterized by the on-site investigators, three independent blinded readers (BR) (BR 1, BR 2 and BR 3) and majority readers (the outcome determined by at least two of the blinded readers). A segment was assessable if it was visualized along its entire length and if any region of stenosis, was measured reliably. There were 21 segments of the supra-aortic arteries assessed per participant.

  • Sensitivity for Detection of Clinically Significant Disease Using Gadobutrol-Enhanced MRA and Unenhanced MRA [ Time Frame: Images were taken pre-injection and post-injection ] [ Designated as safety issue: No ]
    Clinically significant disease was defined as 70 to 99% stenosis of a segment, but not occluded, as assessed by the standard of reference (SoR) (computed tomographic angiography [CTA]; blinded readers). This was determined using the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria. For each segment, the most severe stenosis/narrowing was identified and considered for the evaluation of clinically significant disease. In case of multiple stenosis in any one segment, the most severe stenosis in the segment was recorded.

  • Specificity for Exclusion of Clinically Significant Disease Using Gadobutrol-Enhanced MRA and Unenhanced MRA [ Time Frame: Images were taken pre-injection and post-injection ] [ Designated as safety issue: No ]
    Clinically significant disease was defined as 70 to 99% stenosis of a segment, but not occluded, as assessed by the SoR (CTA; blinded readers). This was determined using the NASCET criteria. For each segment, the most severe stenosis/narrowing was identified and considered for the evaluation of clinically significant disease. In case of multiple stenosis in any one segment, the most severe stenosis in the segment was recorded.

  • Minimum Gadobutrol Performance for Sensitivity: Sensitivity > 50% [ Time Frame: Images were taken pre-injection and post-injection ] [ Designated as safety issue: No ]
    Clinically significant disease was defined as 70 to 99% stenosis of a segment, but not occluded as assessed by the SoR (CTA; blinded readers). For each segment, the most severe stenosis/narrowing was identified and considered for the evaluation of clinically significant disease. Gadobutrol minimum performance criteria was based on a stenosis of 50% calculated from the native vessel diameter.

  • Minimum Gadobutrol Performance for Specificity: Specificity > 50% [ Time Frame: Images were taken pre-injection and post-injection ] [ Designated as safety issue: No ]
    Clinically significant disease was defined as 70 to 99% stenosis of a segment, but not occluded as assessed by the SoR (CTA; blinded readers). For each segment, the most severe stenosis/narrowing was identified and considered for the evaluation of clinically significant disease. Gadobutrol minimum performance criteria was based on a stenosis of 50% calculated from the native vessel diameter.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ease of expression, the following abbreviations will be used: Diameter (DIA), Blinded Reader (BR), Clinical Investigator (CI).

  • The Percentage of Segments With Artifacts Presence [ Time Frame: Images were taken pre-injection and post-injection ] [ Designated as safety issue: No ]
    Artifacts were collected for the MRA images on a segmental basis.

  • Types of Artifacts on a Segment Basis by Blinded Reader 1 [ Time Frame: Images were taken pre-injection and post-injection ] [ Designated as safety issue: No ]
    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 on a Segment Basis by Blinded Reader 2 [ Time Frame: Images were taken pre-injection and post-injection ] [ Designated as safety issue: No ]
    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 on a Segment Basis by Blinded Reader 3 [ Time Frame: Images were taken pre-injection and post-injection ] [ Designated as safety issue: No ]
    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 Location of Stenosis (>=70%) in the Proximal Segments Assessed by Gadobutrol-Enhanced MRA and Unenhanced MRA [ Time Frame: Images were taken pre-injection and post-injection ] [ Designated as safety issue: No ]
    Location within a segment was based on the point of greatest stenosis and was recorded for stenosis >=70% (including occlusions) as: - At the bifurcation or proximal origin of a segment (occlusion proximal to the origin of the segment); - Within 5 mm of the bifurcation or proximal origin of a segment; - Beyond 5 mm from the bifurcation or proximal origin of a segment.

  • Length of Stenosis (>=70%) in the Proximal Segments Assessed by Gadobutrol-Enhanced MRA and Unenhanced MRA [ Time Frame: Images were taken pre-injection and post-injection ] [ Designated as safety issue: No ]
    The length of stenosis was based on the most proximal (first point) in a segment where a stenosis exceeded 10% and the most distal point (last point) in the segment where a stenosis exceeded 10%. If a stenosis spanned more than one segment then the measurement was only included to the beginning or end (boundary) of the segment being evaluated. If there was no stenosis of >=70% in a segment then the length was designated as 0.

  • The Percentage of Presence of Secondary Radiologic Indicators for Diagnosis of Clinically Relevant Disease [ Time Frame: Images were taken pre-injection and post-injection ] [ Designated as safety issue: No ]
    Each segment was assessed for secondary signs of stenosis for diagnosis of clinically significant disease. The following indicators were considered for the MRA studies: - post-stenotic dilation or ulceration (segmental), - post-stenotic signal dropout, narrowing and intensity reduction, and - thrombus. Each of the three parameters were assessed as present or absent in the region distal to the stenosis. If they were found in any segment distal to the stenosis then they were assessed as present.

  • Type of Secondary Radiologic Indicators for Diagnosis of Clinically Relevant Disease [ Time Frame: Images were taken pre-injection and post-injection ] [ Designated as safety issue: No ]
    Each segment was assessed for secondary signs of stenosis for diagnosis of clinically significant disease. The following indicators were considered for the MRA studies: - post-stenotic dilation or ulceration (segmental), - post-stenotic signal dropout, narrowing and intensity reduction, and - thrombus. Each of the three parameters were assessed as present or absent in the region distal to the stenosis. If they were found in any segment distal to the stenosis then they were assessed as present. If there were tandem (serial) stenosis in a vessel then the secondary signs were assigned to the stenosis of >=70% that was proximal and closest in proximity to the secondary sign.

  • Diagnostic Confidence by the Blinded Readers Using Gadobutrol-Enhanced MRA and Unenhanced MRA [ Time Frame: Images were taken pre-injection and post-injection ] [ Designated as safety issue: No ]
    Diagnostic confidence was evaluated to determine the level of certainty that the blinded readers assigned to a diagnosis for each segment. This was defined as the degree of confidence that the information on the MRA images represented the true and complete clinical picture of a particular segment. The degree of confidence was rated on a 4-point scale: 1 = Not confident, 2 = Somewhat confident, 3 = Confident, and 4 = Very confident.

  • The Percentage of Participants With Additional Imaging Studies Recommended by the Blinded Readers and the Clinical Investigator After Evaluation of the Unenhanced and Gadobutrol-Enhanced MRA Images [ Time Frame: Images were taken pre-injection and post-injection ] [ Designated as safety issue: No ]
    A measure of diagnostic value was the reduction in the number of additional diagnostic imaging studies recommended/ordered. The clinical investigators and the blinded readers were asked if they would have recommended an additional imaging study for each participant and was recorded.

  • Types of Additional Imaging Studies Recommended by the Blinded Readers After Evaluation of the Unenhanced and Gadobutrol-Enhanced MRA Images - Blinded Reader 1 [ Time Frame: Images were taken pre-injection and post-injection ] [ Designated as safety issue: No ]
    An additional imaging study recommended was specified from the following list: Non-contrast MRA, Contrast-enhanced MRA, CTA, Ultrasound, Digital subtraction catheter angiogram (DSCA), and Nuclear medicine study.

  • Types of Additional Imaging Studies Recommended by the Blinded Readers After Evaluation of the Unenhanced and Gadobutrol-Enhanced MRA Images - Blinded Reader 2 [ Time Frame: Images were taken pre-injection and post-injection ] [ Designated as safety issue: No ]
    An additional imaging study recommended was specified from the following list: Non-contrast MRA, Contrast-enhanced MRA, CTA, Ultrasound, Digital subtraction catheter angiogram (DSCA), and Nuclear medicine study.

  • Types of Additional Imaging Studies Recommended by the Blinded Readers After Evaluation of the Unenhanced and Gadobutrol-Enhanced MRA Images - Blinded Reader 3 [ Time Frame: Images were taken pre-injection and post-injection ] [ Designated as safety issue: No ]
    An additional imaging study recommended was specified from the following list: Non-contrast MRA, Contrast-enhanced MRA, CTA, Ultrasound, Digital subtraction catheter angiogram (DSCA), and Nuclear medicine study.

  • Types of Additional Imaging Studies Recommended by the Clinical Investigator After Evaluation of the Unenhanced and Gadobutrol-Enhanced MRA Images [ Time Frame: Images were taken pre-injection and post-injection ] [ Designated as safety issue: No ]
    An additional imaging study recommended was specified from the following list: Non-contrast MRA, Contrast-enhanced MRA, CTA, Ultrasound, Digital subtraction catheter angiogram (DSCA), and Nuclear medicine study.


Enrollment: 479
Study Start Date: May 2011
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 Drug: Gadobutrol (Gadovist, BAY86-4875)
A single bolus injection of approx. 0.1mmol/kg

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01344447

  Hide Study Locations
Locations
United States, Arizona
Tucson, Arizona, United States, 85724
United States, California
Newport Beach, California, United States, 92658-6100
United States, Florida
Jacksonville, Florida, United States, 32209
United States, Georgia
Savannah, Georgia, United States, 31406
United States, Kentucky
Louisville, Kentucky, United States, 40202
United States, Maryland
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Boston, Massachusetts, United States, 02114
Boston, Massachusetts, United States, 02115
United States, Michigan
Ann Arbor, Michigan, United States, 48109-0330
United States, Mississippi
Jackson, Mississippi, United States, 39216
United States, New York
Bronx, New York, United States, 10467
New York, New York, United States, 10032
Rochester, New York, United States, 14642
United States, Ohio
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
Hershey, Pennsylvania, United States, 17033
Philadelphia, Pennsylvania, United States, 19104
United States, Rhode Island
Providence, Rhode Island, United States, 02903
United States, Tennessee
Memphis, Tennessee, United States, 38104
United States, Washington
Seattle, Washington, United States, 98195
United States, Wisconsin
Madison, Wisconsin, United States, 53792
Milwaukee, Wisconsin, United States, 53215
Argentina
Adrogué, Buenos Aires, Argentina, B1846DWA
Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1115AAB
Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1425BEE
Rosario, Santa Fe, Argentina, S2000DTC
Australia, New South Wales
New Lambton Heights, New South Wales, Australia, 2305
Australia, South Australia
Bedford Park, South Australia, Australia, 5042
Australia, Victoria
Clayton, Victoria, Australia, 3168
Parkville, Victoria, Australia, 3052
Austria
Innsbruck, Tirol, Austria, 6020
Wien, Austria, 1090
Wiener Neustadt, Austria, 2700
Brazil
São Paulo, Sao Paulo, Brazil, 05651-900
Sao Paulo, Brazil, 01323-001
Sao Paulo, Brazil, 05403-900
China
Shanghai, China, 200032
Shanghai, China, 200433
Czech Republic
Brno, Czech Republic, 62500
Plzen, Czech Republic, 304 60
Praha 2, Czech Republic, 128 21
Praha 5, Czech Republic, 150 30
France
Brest Cedex, France, 29609
BRON Cedex, France, 69677
Marseille, France, 13385
Paris, France, 75877
Paris Cedex 15, France, 75908
Germany
Karlsruhe, Baden-Württemberg, Germany, 76133
Augsburg, Bayern, Germany, 865156
Erlangen, Bayern, Germany, 91054
Frankfurt, Hessen, Germany, 60596
Münster, Nordrhein-Westfalen, Germany, 48145
Kiel, Schleswig-Holstein, Germany, 24105
Jena, Thüringen, Germany, 07740
Dresden, Germany, 01307
Italy
Lagosanto, Ferrara, Italy, 44023
Massa, Massa-Carrara, Italy, 54100
Mestre, Venezia, Italy, 30174
Aosta, Italy, 11100
Catania, Italy, 95123
Roma, Italy, 00168
Korea, Republic of
Donggu,, Gwangju Gwang''yeogsi, Korea, Republic of, 501-757
Seoul, Korea, Republic of, 120-752
Seoul, Korea, Republic of, 135-710
Seoul, Korea, Republic of, 138-736
Poland
Bydgoszcz, Poland, 85-094
Lodz, Poland, 90-153
Warszawa, Poland, 02-097
Wroclaw, Poland, 50-556
Zamosc, Poland, 22-400
Sweden
Linköping, Sweden, 581 85
Uppsala, Sweden, 751 85
Switzerland
Aarau, Aargau, Switzerland, 5001
St. Gallen, Sankt Gallen, Switzerland, 9007
Bern, Switzerland, 3010
Luzern, Switzerland, 6000
Turkey
Antalya, Turkey, 07059
Erzurum, Turkey, 25240
Istanbul, Turkey
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01344447     History of Changes
Other Study ID Numbers: 14607, 2010-023001-36
Study First Received: April 5, 2011
Results First Received: May 27, 2015
Last Updated: July 29, 2015
Health Authority: Argentina: Ministry of Health
Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Federal Office for Safety in Health Care
Brazil: Ministry of Health
China: Food and Drug Administration
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Italy: The Italian Medicines Agency
Korea: Food and Drug Administration
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Sweden: Medical Products Agency
Switzerland: Swissmedic
Turkey: Ministry of Health
United States: Food and Drug Administration

Keywords provided by Bayer:
Supra-aortic vascular disease
MRA
CTA
Males and females aged 18 years or older
Stroke
Transient Ischemic Attack (TIA)

Additional relevant MeSH terms:
Carotid Stenosis
Vascular Diseases
Arterial Occlusive Diseases
Brain Diseases
Cardiovascular Diseases
Carotid Artery Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Nervous System Diseases
Gadobutrol
Contrast Media
Diagnostic Uses of Chemicals
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 26, 2015