Phase 3
N=478
Gadobutrol / Gadavist-enhanced Cardiac Magnetic Resonance Imaging (CMRI) to Detect Coronary Artery Disease (CAD)
Coronary Artery Disease
Bottom Line
View on ClinicalTrials.gov: NCT01890434 ↗Enrolled (actual)
478
Serious AEs
0.8%
Results posted
May 2018
Primary outcome: Primary: Presence of a Myocardial Perfusion Defect Indicating Significant CAD Per Participant on Gadobutrol-enhanced CMRI - Primary Analysis of Sensitivity Based on Blinded Readers' Assessment — 64.7; 56.0; 61.3 Sensitivity %
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Gadobutrol (Gadavist, Gadovist, BAY86-4875) (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Bayer
- Primary completion
- Aug 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Presence of a Myocardial Perfusion Defect Indicating Significant CAD Per Participant on Gadobutrol-enhanced CMRI - Primary Analysis of Sensitivity Based on Blinded Readers' Assessment |
64.7; 56.0; 61.3 | — |
| PRIMARY Presence of a Myocardial Perfusion Defect Indicating Significant CAD Per Participant on Gadobutrol-enhanced CMRI - Additional Secondary Analysis of Sensitivity Based on Blinded Readers' Assessment |
77.1; 71.4; 76.2 | — |
| PRIMARY Absence of Myocardial Perfusion Defect Excluding Significant CAD Per Participant on Gadobutrol-enhanced CMRI - Primary Analysis of Specificity Based on Blinded Readers' Assessment |
85.3; 88.7; 89.5 | — |
| PRIMARY Absence of a Myocardial Perfusion Defect Excluding Significant CAD Per Participant on Gadobutrol-enhanced CMRI - Additional Secondary Analysis of Specificity Based on Blinded Readers' Assessment |
82.0; 87.3; 86.9 | — |
| PRIMARY 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 |
64.7; 56.0; 61.3; 48.0; 30.0; 29.3 | 0.00009 sig |
| PRIMARY 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 |
77.1; 71.4; 76.2; 56.2; 35.2; 35.2 | 0.00005 sig |
| SECONDARY Presence of a Myocardial Perfusion Defect Indicating Significant CAD Per Participant on Gadobutrol-enhanced CMRI - Secondary Analysis of Sensitivity Based on Investigator's Assessment |
72.0 | — |
| SECONDARY Presence of a Myocardial Perfusion Defect Indicating Significant CAD Per Participant on Gadobutrol-enhanced CMRI - Additional Secondary Analysis of Sensitivity Based on Investigator's Assessment |
85.7 | — |
| SECONDARY Absence of a Myocardial Perfusion Defect Excluding Significant CAD Per Participant on Gadobutrol-enhanced CMRI - Secondary Analysis of Specificity Based on Investigator's Assessment |
85.8 | — |
| SECONDARY 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 |
81.7 | — |
| SECONDARY 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 the Investigator's Assessment |
72.0; 50.7 | <0.0001 sig |
| SECONDARY Presence of a Myocardial Perfusion Defect Indicating Significant CAD Per Participant on Gadobutrol-enhanced CMRI and Unenhanced Wall Motion CMRI Images - Additional Secondary Analysis of Sensitivity Comparison Based on the Investigator's Assessment |
85.7; 61.0 | — |
| SECONDARY Presence of a Myocardial Perfusion Defect Indicating Significant CAD Per Participant on Gadobutrol-enhanced CMRI Versus GSPECT - Secondary Analysis of Sensitivity Comparison Based on Majority Blinded Reader's and Investigator's Assessment |
60.0; 72.3; 54.3; 72.3 | 0.2733 |
| SECONDARY Presence of a Myocardial Perfusion Defect Indicating Significant CAD Per Participant on Gadobutrol-enhanced CMRI and GSPECT - Additional Secondary Analysis of Sensitivity Based on Majority Blinded Reader's and Investigator's Assessment |
78.8; 86.7; 64.9; 83.0 | — |
| SECONDARY Absence of a Myocardial Perfusion Defect Excluding Significant CAD Per Participant on Gadobutrol-enhanced CMRI Versus GSPECT -- Secondary Analysis of Specificity Comparison Based on Majority Blinded Reader's and Investigator's Assessment |
92.1; 85.3; 81.0; 77.5 | 0.0010 sig |
| SECONDARY Absence of a Myocardial Perfusion Defect Excluding Significant CAD Per Participant on Gadobutrol-enhanced CMRI and GSPECT - Additional Secondary Analysis of Specificity Based on Majority Blinded Reader's and Investigator's Assessment |
86.6; 81.7; 78.9; 73.6 | — |
| SECONDARY Localization of a Myocardial Perfusion Defect to Each Coronary Territory on Gadobutrol-enhanced CMRI - Secondary Analysis of Sensitivity Based on Blinded Readers' and Investigator's Assessment |
54.8; 40.4; 46.2; 48.1; 52.9; 63.7 | — |
| SECONDARY Localization of a Myocardial Perfusion Defect to LAD and Non-LAD Territory on GSPECT - Secondary Analysis of Sensitivity Based on Blinded Readers' and Investigator's Assessment |
32.9; 31.4; 37.1; 31.4; 43.9; 58.0 | — |
| SECONDARY Localization of a Myocardial Perfusion Defect to Each Coronary Territory on Gadobutrol-enhanced CMRI - Additional Secondary Analysis of Sensitivity Based on Blinded Readers' and Investigator's Assessment |
74.6; 58.7; 63.5; 68.3; 71.4; 68.8 | — |
| SECONDARY Localization of a Myocardial Perfusion Defect to Each Coronary Territory on Gadobutrol-enhanced CMRI - Secondary Analysis of Specificity Based on Blinded Readers' and Investigator's Assessment |
89.9; 92.4; 92.4; 92.4; 89.9; 83.6 | — |
| SECONDARY Localization of a Myocardial Perfusion Defect to LAD and Non-LAD Territory on GSPECT - Secondary Analysis of Specificity Based on Blinded Readers' and Investigator's Assessment |
88.6; 89.5; 90.9; 91.8; 88.0; 75.0 | — |
| SECONDARY Localization of a Myocardial Perfusion Defect to Each Coronary Territory on Gadobutrol-enhanced CMRI - Additional Secondary Analysis of Specificity Based on Blinded Readers' and Investigator's Assessment |
86.8; 91.1; 89.8; 85.6; 79.1; 85.5 | — |
| SECONDARY Detection of Myocardial Perfusion Defect(s) on Gadobutrol-enhanced CMRI in Participants With Significant LMS Stenosis - Based on Blinded Readers' and Investigator's Assessment |
1; 1; 2; 1; 0; 1 | — |
| SECONDARY Presence of a Myocardial Perfusion Defect Indicating Significant CAD in Participants With Single or Multi-vessel Disease Evaluated on Gadobutrol-enhanced CMRI - Secondary Analysis of Sensitivity Based on Blinded Readers' and Investigator's Assessment |
45.8; 32.2; 39.0; 45.8; 77.4; 72.6 | — |
| SECONDARY Presence of a Myocardial Perfusion Defect Indicating Significant CAD in Participants With Single-vessel Disease Evaluated on Gadobutrol-enhanced CMRI and GSPECT - Additional Secondary Analysis of Sensitivity by Majority Blinded Reader and Investigator |
66.7; 70.4; 21.1; 61.5 | — |
| SECONDARY Presence of a Myocardial Perfusion Defect Indicating Significant CAD in Participants With Multi-vessel Disease Evaluated on Gadobutrol-enhanced CMRI and GSPECT - Additional Secondary Analysis of Sensitivity by Majority Blinded Reader and Investigator |
81.1; 90.5; 77.6; 89.9 | — |
| SECONDARY Number 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 Assessment |
310; 74; 4; 1; 300; 71 | — |
Summary
Subjects 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 subject in the study may range from 2 days to 4-6 weeks. One to four visits to the study doctor will be required.
The primary objective of this study is to demonstrate that sensitivity and specificity of gadobutrol-enhanced cardiac magnetic resonance imaging (CMRI) exceed pre-specified minimum performance thresholds of 60% and 55%, respectively, and to show superior sensitivity over unenhanced wall motion CMRI at vasodilator rest/stress for the detection of significant CAD. The CMR images acquired with a uniform imaging acquisition software will be evaluated either against the results from routine clinical Coronary Angiography (CA) or Computed Tomography Angiography (CTA), which are the standard of reference.
CMRI and CA/CTA images will be collected for an independent image review (blinded read).
Eligibility Criteria
Inclusion Criteria
- Male or female subjects aged ≥18 years
- Subjects with suspected or known CAD based on signs and/or (typical or atypical) chest pain who have routine CA without intervention within plus/minus 4 weeks of gadobutrol-enhanced CMRI or subjects at low risk of CAD with / or scheduled to get a CTA for the purpose of exclusion of CAD within plus/minus 6 weeks of gadobutrol-enhanced CMRI
- Willingness to undergo unenhanced wall motion and gadobutrol-enhanced CMRI at stress/rest and gated single photon emission computed tomography (GSPECT, if GSPECT will be a study procedure)
- Women of childbearing potential (e.g. age < 60y, no history of surgical sterilization or hysterectomy): use of contraception and a negative pregnancy test
- Subjects who are scheduled for / have undergone routine GSPECT or undergo GSPECT as a study procedure at stress and at rest within ± 4 weeks of gadobutrol-enhanced CMRI
Exclusion Criteria
- 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 subject 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
Data sourced from ClinicalTrials.gov (NCT01890434). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.