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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 478
- 主要终点
- 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
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Gadobutrol 0.1 mmol/kg body weight
Participants received gadobutrol at the total approved standard dose of 0.1 millimole per kilogram body weight (mmol/kg BW) in 2 separate bolus injections: 0.05 mmol/kg BW at peak pharmacologic stress and 0.05 mmol/kg BW at rest via a power injector.
干预措施: Gadobutrol (Gadavist, Gadovist, BAY86-4875) (Drug)
结局指标
主要结局
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
时间窗: 0 to 30/40 min post-injection
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 QCA stenosis of \>=70%, and 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 (CA or CTA \[only if disease can be unequivocally rejected\]). Sensitivity= true positive/ (true positive + false negative). This additional secondary analysis of sensitivity was retrospective analysis.
Absence of Myocardial Perfusion Defect Excluding Significant CAD Per Participant on Gadobutrol-enhanced CMRI - Primary Analysis of Specificity Based on Blinded Readers' Assessment
时间窗: 0 to 30/40 min post-injection
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 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. Significant CAD was defined as QCA stenosis of \>=50% for primary analysis, and was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced CMRI verified by SoR (CA or CTA \[only if disease can be unequivocally rejected\]). Specificity= true negative/ (true negative + false positive).
Presence of a Myocardial Perfusion Defect Indicating Significant CAD Per Participant on Gadobutrol-enhanced CMRI - Primary Analysis of Sensitivity Based on Blinded Readers' Assessment
时间窗: 0 to 30/40 min post-injection
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 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. 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, coronary angiography \[CA\] or computed tomography angiography \[CTA, only if disease can be unequivocally rejected\]). Sensitivity= true positive/ (true positive + false negative).
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
时间窗: 0 to 30/40 min post-injection
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 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. Significant CAD was defined as QCA stenosis of \>=70%, and was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced CMRI verified by SoR (CA or CTA \[only if disease can be unequivocally rejected\]). Specificity= true negative/ (true negative + false positive). This additional secondary analysis of specificity was retrospective analysis.
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
时间窗: 0 to 30/40 min post-injection
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 QCA stenosis of \>=50% for primary analysis, and 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 (CA or CTA \[only if disease can be unequivocally rejected\]). Sensitivity= true positive/ (true positive + false negative).
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
时间窗: 0 to 30/40 min post-injection
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 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. Significant CAD was defined as QCA stenosis of \>=70%, and was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced CMRI verified by SoR (CA or CTA \[only if disease can be unequivocally rejected\]). Sensitivity= true positive/ (true positive + false negative). This additional secondary analysis of sensitivity was retrospective analysis.
次要结局
- Absence of a Myocardial Perfusion Defect Excluding Significant CAD Per Participant on Gadobutrol-enhanced CMRI - Secondary Analysis of Specificity Based on Investigator's Assessment(0 to 30/40 min post-injection)
- 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(0 to 30/40 min post-injection)
- 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(0 to 30/40 min post-injection)
- 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(0 to 30/40 min post-injection)
- 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(0 to 30/40 min post-injection)
- Detection of Myocardial Perfusion Defect(s) on Gadobutrol-enhanced CMRI in Participants With Significant LMS Stenosis - Based on Blinded Readers' and Investigator's Assessment(0 to 30/40 min post-injection)
- 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(0 to 30/40 min post-injection)
- Presence of a Myocardial Perfusion Defect Indicating Significant CAD Per Participant on Gadobutrol-enhanced CMRI - Secondary Analysis of Sensitivity Based on Investigator's Assessment(0 to 30/40 min post-injection)
- 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(0 to 30/40 min post-injection)
- 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(0 to 30/40 min post-injection)
- 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(0 to 30/40 min post-injection)
- 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(0 to 30/40 min post-injection)
- 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(0 to 30/40 min post-injection)
- 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(0 to 30/40 min post-injection)
- 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(0 to 30/40 min post-injection)
- 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(0 to 30/40 min post-injection)
- 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(0 to 30/40 min post-injection)
- 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(0 to 30/40 min post-injection)
- 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(0 to 30/40 min post-injection)
- 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(0 to 30/40 min post-injection)
- 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(0 to 30/40 min post-injection)