check_circleStudy Completed

Coronary Artery Disease

Bayer Identifier:

15961

ClinicalTrials.gov Identifier:

NCT01890421

EudraCT Number:

2012-002563-10

EU CT Number:

Not Available
Gadobutrol/Gadavist-enhanced cardiac magnetic resonance imaging (CMRI) to detect Coronary Artery Disease (CAD)

Trial purpose

Participants being evaluated for suspected or known Coronary artery Disease (CAD) based on signs and/or symptoms, will be invited to participate in the study. The duration for a participant in the study may range from 2 days to 4-6 weeks. One to four visits to the study doctor will be required.
This study will investigate the diagnostic results of gadobutrol-enhanced Cardiac Magnetic Resonance Imaging (CMRI) images regarding the detection (sensitivity) and exclusion (specificity) of coronary artery disease utilizing a uniform image acquisition software. The CMR images will be tested either against the results from routine clinical Coronary Angiography (CA) or those from Computed Tomography Angiography (CTA), which is used as the standard of reference. The CA/CTA may have been performed up to 4 weeks prior to enrollment or be scheduled up to 4/6 weeks after the study.
CMRI and CA/CTA images will be collected for an independent image review (blinded read).

Key Participants Requirements

Sex

Both

Age

18 - N/A
  • - Male or female participants aged ≥18 years
    - Participants with suspected or known CAD based on signs and/or (typical or atypical) chest pain who have routine CA without intervention or CTA within 4 weeks around gadobutrol-enhanced CMRI
    - Willingness to undergo stress/rest CMRI and to follow directions and complete all study procedures
    - Women of childbearing potential (e.g. age < 60y, no history of surgical sterilization or hysterectomy): use of contraception and a negative pregnancy test
  • - Suspected clinical instability or unpredictability of the clinical course during the study period
    - Contraindication to the cardiac MRI examination (e.g. inability to hold breath; severe claustrophobia, metallic devices such as pace makers)
    - History of severe allergic or anaphylactoid reaction to any allergen including drugs and contrast agents according to the investigator’s assessment / judgment
    - Estimated glomerular filtration rate (eGFR) value <30 mL/min/1.73 m^2 derived from a serum / blood creatinine result within 2 weeks prior to gadobutrol injection. Any participant on hemodialysis or peritoneal dialysis is excluded from enrollment.
    - Acute renal insufficiency
    - Coronary artery bypass grafting (CABG)
    - Acute myocardial infarction (< 14 days prior to inclusion), unstable angina / acute coronary syndrome, severe congestive heart failure
    - Irregular heart rhythm
    - Condition that precludes the safe administration of pharmacological stressor according to the respective approved label such as sinus node disease, 2nd or 3rd degree atrioventricular block, obstructive lung disease

Trial summary

Enrollment Goal
426
Trial Dates
July 2013 - August 2017
Phase
Phase 3
Could I Receive a placebo
No
Products
Gadavist/Gadovist (Gadobutrol, BAY86-4875)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Withdrawn
Bristol, BS2 8HW, United Kingdom
Withdrawn
Dundee, DD1 9SY, United Kingdom
Completed
Leicester, LE3 9QP, United Kingdom
Completed
London, SW3 6NP, United Kingdom
Withdrawn
Zürich, 8091, Switzerland
Completed
Lugano, 6900, Switzerland
Withdrawn
Bern, 3010, Switzerland
Completed
Saint-Etienne, 42055, France
Completed
Marseille, 13385, France
Completed
Berlin, 13125, Germany
Completed
Essen, 45122, Germany
Withdrawn
Berlin, 10115, Germany
Completed
Tuebingen, 72076, Germany
Completed
Stuttgart, 70376, Germany
Withdrawn
Mannheim, 68167, Germany
Completed
Berlin, 10709, Germany
Completed
Berlin, 12203, Germany
Completed
Auckland, New Zealand
Completed
Seoul, 05030, Korea, Republic Of
Completed
Incheon, 21565, Korea, Republic Of
Completed
Leipzig, 04289, Germany
Completed
Minneapolis, 55455, United States
Completed
Yangsan-si, 50612, Korea, Republic Of
Completed
Seoul, 05505, Korea, Republic Of
Completed
Darmstadt, 64287, Germany
Completed
Göttingen, 37075, Germany
Completed
Bad Krozingen, 79189, Germany
Completed
Bonn, 53115, Germany
Completed
Liverpool, L14 3PE, United Kingdom
Withdrawn
Providence, 02903-4900, United States
Withdrawn
Würzburg, 97080, Germany

Primary Outcome

  • Presence of a Myocardial Perfusion Defect Indicating Significant CAD per Participant on Gadobutrol-enhanced CMRI (Based on RPS) – Primary Analysis of Sensitivity Based on Blinded Readers' Assessment
    Blinded readers evaluated 6 myocardial regions based on regional perfusion score (RPS), 0=normal; 1=abnormal, reversible perfusion defect (stress); 2=abnormal, mixed perfusion defect (reversible and fixed/permanent components); 3=abnormal, fixed/permanent perfusion defect/scar (stress and rest)]. A myocardial region a perfusion defect in case of a RPS of >=1 and was rated to have normal perfusion in case of a RPS of 0. Significant CAD was defined as quantitative coronary angiography (QCA) stenosis of >=50% for primary analysis, and was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced cardiac magnetic resonance imaging (CMRI) verified by standard of reference (SoR). Sensitivity= true positive/ (true positive + false negative).
    date_rangeTime Frame:
    0 to 30/40 minute (min) post-injection
    enhanced_encryption
    Safety Issue:
    No
  • Presence of a Myocardial Perfusion Defect Indicating Significant CAD per Participant on Gadobutrol-enhanced CMRI (Based on RPS) – Additional Secondary analysis of Sensitivity Based on the Blinded Readers' Assessment
    Blinded readers evaluated 6 myocardial regions based on regional perfusion score (RPS), 0=normal; 1=abnormal, reversible perfusion defect (stress); 2=abnormal, mixed perfusion defect (reversible and fixed/permanent components); 3=abnormal, fixed/permanent perfusion defect/scar (stress and rest)]. A myocardial region a perfusion defect in case of a RPS of >=1 and was rated to have normal perfusion in case of a RPS of 0. Significant CAD was defined as quantitative coronary angiography (QCA) stenosis of >=70% for secondary analysis, and was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced cardiac magnetic resonance imaging (CMRI) verified by standard of reference (SoR). Sensitivity= true positive/ (true positive + false negative). This additional secondary analysis of sensitivity was prospective analysis.
    date_rangeTime Frame:
    0 to 30/40 min post-injection
    enhanced_encryption
    Safety Issue:
    No
  • Absence of a Myocardial Perfusion Defect Excluding Significant CAD per Participant on Gadobutrol-enhanced CMRI (Based on RPS) – Primary Analysis of Specificity Based on the Blinded Readers' Assessment
    Blinded readers evaluated 6 myocardial regions based on regional perfusion score (RPS), 0=normal; 1=abnormal, reversible perfusion defect (stress); 2=abnormal, mixed perfusion defect (reversible and fixed/permanent components); 3=abnormal, fixed/permanent perfusion defect/scar (stress and rest)]. A myocardial region a perfusion defect in case of a RPS of >=1 and was rated to have normal perfusion in case of a RPS of 0. Significant CAD was defined as quantitative coronary angiography (QCA) stenosis of >=50% for primary analysis, and was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced cardiac magnetic resonance imaging (CMRI) verified by standard of reference (SoR). Specificity= true negative/ (true negative + false positive).
    date_rangeTime Frame:
    0 to 30/40 min post-injection
    enhanced_encryption
    Safety Issue:
    No
  • Absence of a Myocardial Perfusion Defect Excluding Significant CAD per Participant on Gadobutrol-enhanced CMRI (Based on RPS) – Additional Secondary Analysis of Specificity Based on the Blinded Readers' Assessment
    Blinded readers evaluated 6 myocardial regions based on regional perfusion score (RPS), 0=normal; 1=abnormal, reversible perfusion defect (stress); 2=abnormal, mixed perfusion defect (reversible and fixed/permanent components); 3=abnormal, fixed/permanent perfusion defect/scar (stress and rest)]. A myocardial region a perfusion defect in case of a RPS of >=1 and was rated to have normal perfusion in case of a RPS of 0. Significant CAD was defined as quantitative coronary angiography (QCA) stenosis of >=70% for primary analysis, and was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced cardiac magnetic resonance imaging (CMRI) verified by standard of reference (SoR). Specificity= true negative/ (true negative + false positive). This additional secondary analysis of specificity was prospective analysis.
    date_rangeTime Frame:
    0 to 30/40 min post-injection
    enhanced_encryption
    Safety Issue:
    No
  • Presence of a Myocardial Perfusion Defect Indicating Significant CAD per Participant on Gadobutrol-enhanced CMRI Versus Unenhanced Wall Motion CMRI Images – Primary Analysis of Sensitivity Comparison Based on the Blinded Readers' Assessment
    Presence of a myocardial perfusion defect on gadobutrol-enhanced CMRI versus the presence of wall motion abnormalities on unenhanced CMRI images (based on regional perfusion/regional wall motion score of the 6 myocardial regions) was calculated by blinded readers' assessment. Significant CAD was defined as quantitative coronary angiography (QCA) stenosis of >=50% for primary analysis, and was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced cardiac magnetic resonance imaging (CMRI) verified by standard of reference (SoR). Sensitivity= true positive/ (true positive + false negative).
    date_rangeTime Frame:
    0 to 30/40 min post-injection
    enhanced_encryption
    Safety Issue:
    No
  • Presence of a Myocardial Perfusion Defect Indicating Significant CAD per Participant on Gadobutrol-enhanced CMRI Versus Unenhanced Wall Motion CMRI Images – Additional Secondary Analysis of Sensitivity Comparison Based on the Blinded Readers' Assessment
    Presence of a myocardial perfusion defect on gadobutrol-enhanced CMRI versus the presence of wall motion abnormalities on unenhanced CMRI images (based on regional perfusion/regional wall motion score of the 6 myocardial regions) was calculated by blinded readers' assessment. Significant CAD was defined as quantitative coronary angiography (QCA) stenosis of >=70% for primary analysis, and was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced cardiac magnetic resonance imaging (CMRI) verified by standard of reference (SoR). Sensitivity= true positive/ (true positive + false negative). This additional secondary analysis of sensitivity was prospective analysis.
    date_rangeTime Frame:
    0 to 30/40 min post-injection
    enhanced_encryption
    Safety Issue:
    No

Secondary Outcome

  • Presence of a Myocardial Perfusion Defect Indicating Significant CAD per Participant on Gadobutrol-enhanced CMRI – Secondary Analysis of Sensitivity Based on Investigator's Assessment
    Presence of a myocardial perfusion defect on gadobutrol-enhanced CMRI versus the presence of wall motion abnormalities on unenhanced CMRI images (based on regional perfusion/regional wall motion score of the 6 myocardial regions) was calculated by investigator's assessment. Significant CAD was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced CMRI or the presence of wall motion abnormalities on unenhanced CMRI images verified by SoR (significant CAD defined as QCA stenosis of >=50%). Sensitivity= true positive/ (true positive + false negative).
    date_rangeTime Frame:
    0 to 30/40 min post-injection
    enhanced_encryption
    Safety Issue:
    No
  • Presence of a Myocardial Perfusion Defect Indicating Significant CAD per Participant on Gadobutrol-enhanced CMRI – Additional Secondary Analysis of Sensitivity Comparison Based on Investigator's Assessment
    Presence of a myocardial perfusion defect on gadobutrol-enhanced CMRI versus the presence of wall motion abnormalities on unenhanced CMRI images (based on regional perfusion/regional wall motion score of the 6 myocardial regions) was calculated by investigator's assessment. Significant CAD was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced CMRI or the presence of wall motion abnormalities on unenhanced CMRI images verified by SoR (significant CAD defined as QCA stenosis of >=70%). Sensitivity= true positive/ (true positive + false negative). This additional secondary analysis of sensitivity was prospective analysis.
    date_rangeTime Frame:
    0 to 30/40 min post-injection
    enhanced_encryption
    Safety Issue:
    No
  • Absence of a Myocardial Perfusion Defect Excluding Significant CAD per Participant on Gadobutrol-enhanced CMRI – Secondary Analysis of Specificity Based on Investigator's Assessment
    Investigator’s assessment evaluated 6 myocardial regions based on regional perfusion score (RPS), 0=normal; 1=abnormal, reversible perfusion defect (stress); 2=abnormal, mixed perfusion defect (reversible and fixed/permanent components); 3=abnormal, fixed/permanent perfusion defect/scar (stress and rest). A myocardial region was rated to have a perfusion defect in case of a RPS of >=1 and was rated to have normal perfusion in case of a RPS of 0. The investigator’s assessment of participant-based specificity of gadobutrol-enhanced CMRI was analyzed with significant CAD defined as maximum stenosis severity of >=50% by QCA, which were secondary analysis. Specificity= true negative/ (true negative + false positive).
    date_rangeTime Frame:
    0 to 30/40 min post-injection
    enhanced_encryption
    Safety Issue:
    No
  • Absence of a Myocardial Perfusion Defect Excluding Significant CAD per Participant on Gadobutrol-enhanced CMRI – Additional Secondary Analysis of Specificity Based on Investigator's Assessment
    Investigator’s assessment evaluated 6 myocardial regions based on regional perfusion score (RPS), 0=normal; 1=abnormal, reversible perfusion defect (stress); 2=abnormal, mixed perfusion defect (reversible and fixed/permanent components); 3=abnormal, fixed/permanent perfusion defect/scar (stress and rest). A myocardial region was rated to have a perfusion defect in case of a RPS of >=1 and was rated to have normal perfusion in case of a RPS of 0. The investigator’s assessment of participant-based specificity of gadobutrol-enhanced CMRI was analyzed with significant CAD defined as maximum stenosis severity of >=70% by QCA, which were secondary analysis. Specificity= true negative/ (true negative + false positive). This additional secondary analysis of specificity was prospective analysis.
    date_rangeTime Frame:
    0 to 30/40 min post-injection
    enhanced_encryption
    Safety Issue:
    No
  • Presence of a Myocardial Perfusion Defect Indicating Significant CAD per Participant on Gadobutrol-enhanced CMRI Versus Unenhanced Wall Motion CMRI Images – Secondary Analysis of Sensitivity Comparison Based on Investigator's Assessment
    Investigator’s assessment evaluated 6 myocardial regions based on regional perfusion score (RPS), 0=normal; 1=abnormal, reversible perfusion defect (stress); 2=abnormal, mixed perfusion defect (reversible and fixed/permanent components); 3=abnormal, fixed/permanent perfusion defect/scar (stress and rest). A myocardial region was rated to have a perfusion defect in case of a RPS of >=1 and was rated to have normal perfusion in case of a RPS of 0. The investigator’s assessment of participant-based sensitivity and specificity of gadobutrol-enhanced CMRI was analyzed with significant CAD defined as maximum stenosis severity of >=50% by QCA, which were secondary analysis. Sensitivity= true positive/ (true positive + false negative).
    date_rangeTime Frame:
    0 to 30/40 min post-injection
    enhanced_encryption
    Safety Issue:
    No
  • Presence of a Myocardial Perfusion Defect Indicating Significant CAD per Participant on Gadobutrol-enhanced CMRI Versus Unenhanced Wall Motion CMRI Images – Additional Secondary Analysis of Sensitivity Comparison Based on Investigator's Assessment
    Investigator’s assessment evaluated 6 myocardial regions based on regional perfusion score (RPS), 0=normal; 1=abnormal, reversible perfusion defect (stress); 2=abnormal, mixed perfusion defect (reversible and fixed/permanent components); 3=abnormal, fixed/permanent perfusion defect/scar (stress and rest). A myocardial region was rated to have a perfusion defect in case of a RPS of >=1 and was rated to have normal perfusion in case of a RPS of 0. The investigator’s assessment of participant-based sensitivity and specificity of gadobutrol-enhanced CMRI was analyzed with significant CAD defined as maximum stenosis severity of >=70% by QCA, which were secondary analysis. Sensitivity= true positive/ (true positive + false negative). This additional secondary analysis of sensitivity was prospective analysis.
    date_rangeTime Frame:
    0 to 30/40 min post-injection
    enhanced_encryption
    Safety Issue:
    No
  • Localization of a Myocardial Perfusion Defect to a Coronary Territory on Gadobutrol-Enhanced CMRI – Secondary Analysis of Sensitivity Based on Blinded Readers' and Investigator's Assessments
    Sensitivity was calculated coronary territory based, a coronary territory (left anterior descending artery [LAD] / non-LAD / right coronary artery [RCA] / left circumflex artery [LCX]) was rated positive for significant CAD (significant CAD defined as QCA stenosis of>=50%), if >=1 myocardial region within the same coronary territory showed a myocardial perfusion defect with a RPS of >=1. A coronary territory(LAD / non-LAD) was rated negative for significant CAD, if no myocardial region within the respective coronary territory showed a myocardial perfusion defect (RPS 0). Sensitivity was displayed for all 3 blinded readers and the investigator.
    date_rangeTime Frame:
    0 to 30/40 min post-injection
    enhanced_encryption
    Safety Issue:
    No
  • Localization of a Myocardial Perfusion Defect to a Coronary Territory on Gadobutrol-enhanced CMRI – Additional Secondary Analysis of Sensitivity Based on Blinded Readers' and Investigator's Assessments
    Sensitivity was calculated coronary territory based, a coronary territory (LAD / non-LAD / RCA / LCX) was rated positive for significant CAD (significant CAD defined as QCA stenosis of >=70%), if >=1 myocardial region within the same coronary territory showed a myocardial perfusion defect with a RPS of >=1. A coronary territory (LAD / non-LAD) was rated negative for significant CAD, if no myocardial region within the respective coronary territory showed a myocardial perfusion defect (RPS 0). Sensitivity was displayed for all 3 blinded readers and the investigator. This additional secondary analysis of sensitivity was prospective analysis.
    date_rangeTime Frame:
    0 to 30/40 min post-injection
    enhanced_encryption
    Safety Issue:
    No
  • Localization of a Myocardial Perfusion Defect to a Coronary Territory on Gadobutrol-enhanced CMRI – Secondary Analysis of Specificity Based on Blinded Readers' and Investigator's Assessments
    Specificity was calculated coronary territory based, a coronary territory (LAD / non-LAD / RCA / LCX) was rated positive for significant CAD (significant CAD defined as QCA stenosis of >=50%), if >=1 myocardial region within the same coronary territory showed a myocardial perfusion defect with a RPS of >=1. A coronary territory (LAD / non-LAD) was rated negative for significant CAD, if no myocardial region within the respective coronary territory showed a myocardial perfusion defect (RPS 0). Specificity was displayed for all 3 blinded readers and the investigator.
    date_rangeTime Frame:
    0 to 30/40 min post-injection
    enhanced_encryption
    Safety Issue:
    No
  • Localization of a Myocardial Perfusion Defect to a Coronary Territory on Gadobutrol-enhanced CMRI – Additional Secondary Analysis of Specificity Based on Blinded Readers' and Investigator's Assessments
    Specificity was calculated coronary territory based, a coronary territory (LAD / non-LAD / RCA / LCX) was rated positive for significant CAD (significant CAD defined as QCA stenosis of >=70%), if >=1 myocardial region within the same coronary territory showed a myocardial perfusion defect with a RPS of >=1. A coronary territory (LAD / non-LAD) was rated negative for significant CAD, if no myocardial region within the respective coronary territory showed a myocardial perfusion defect (RPS 0). Specificity was displayed for all 3 blinded readers and the investigator. This additional secondary analysis of specificity was prospective analysis.
    date_rangeTime Frame:
    0 to 30/40 min post-injection
    enhanced_encryption
    Safety Issue:
    No
  • Detection of Myocardial Perfusion Defect(s) on Gadobutrol-enhanced CMRI in Participants with Significant LMS Stenosis – Based on Blinded Readers' and Investigator's Assessments
    Sensitivity was calculated for detection of myocardial perfusion defects on gadobutrol-enhanced CMRI in participants with significant left main stem (LMS) stenosis and the myocardial perfusion defect pattern was described. If >=1 myocardial region showed a myocardial perfusion defect with a RPS of >=1, participants will be rated positive for significant CAD (significant CAD defined as QCA stenosis of >=50%). Sensitivity= true positive/ (true positive + false negative).
    date_rangeTime Frame:
    0 to 30/40 min post-injection
    enhanced_encryption
    Safety Issue:
    No
  • Presence/Absence of a MPD Indicating/Excluding Significant CAD in Participants With Multi Versus Single Vessel Disease Evaluated on Gadobutrol-enhanced CMRI-Secondary Analysis of Sensitivity Based on Blinded Readers' and Investigator's Assessments
    Sensitivity was calculated for detection of myocardial perfusion defects (MPD) on gadobutrol-enhanced CMRI in participants with single and multi-vessel diseases. If >=1 myocardial region showed a myocardial perfusion defect with a RPS of >=1, participants will be rated positive for significant CAD (significant CAD defined as QCA stenosis of >=50%). Sensitivity= true positive/ (true positive + false negative).
    date_rangeTime Frame:
    0 to 30/40 min post-injection
    enhanced_encryption
    Safety Issue:
    No
  • Presence/Absence of a MPD Indicating/Excluding Significant CAD in Participants With Multi Vs Single Vessel Disease Evaluated on Gadobutrol-enhanced CMRI-Additional Secondary Analysis of Sensitivity Based on Blinded Readers' and Investigator's Assessments
    Sensitivity was calculated for detection of MPD on gadobutrol-enhanced CMRI in participants with single and multi-vessel diseases. If >=1 myocardial region showed a myocardial perfusion defect with a RPS of >=1, participants will be rated positive for significant CAD (significant CAD defined as QCA stenosis of >=70%). Sensitivity= true positive/ (true positive + false negative). This additional secondary analysis of sensitivity was prospective analysis.
    date_rangeTime Frame:
    0 to 30/40 min post-injection
    enhanced_encryption
    Safety Issue:
    No
  • Percentage of Participants by Their Lowest Confidence in Diagnosis Obtained on Gadobutrol-enhanced CMRI and Unenhanced Wall Motion CMRI – Based on Blinded Readers' and Investigator's Assessments
    Score for confidence in diagnosis (not confident, somewhat confident, and confident) was described descriptively for each of the 6 myocardial regions. The frequency over the worst confidence in diagnosis obtained within a participant was displayed. All these analyses were done separately for gadobutrol-enhanced CMRI and unenhanced wall motion CMRI.
    date_rangeTime Frame:
    0 to 30/40 min post-injection
    enhanced_encryption
    Safety Issue:
    No

Trial design

Multicenter open-label study to evaluate efficacy of gadobutrol-enhanced cardiac magnetic resonance imaging (CMRI) for detection of significant coronary artery disease (CAD) in subjects with known or suspected CAD by a blinded image analysis
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Diagnostic
Allocation
N/A
Blinding
Open Label
Assignment
Single Group Assignment
Trial Arms
1

Additional Information

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