Trial Outcomes & Findings for Gadobutrol / Gadavist-enhanced Cardiac Magnetic Resonance Imaging (CMRI) to Detect Coronary Artery Disease (CAD) (NCT NCT01890434)

NCT ID: NCT01890434

Last Updated: 2019-07-31

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 478 participants
• Primary outcome timeframe: 0 to 30/40 min post-injection
• Results posted on: 2019-07-31

Participant Flow

The study was conducted at 24 centers across 4 countries, between 26 August 2013 (first patient first visit) and 06 August 2016 (last patient last visit).

Overall, 504 participants signed the informed consent, of which 14 did not finish their baseline visit (7 screening failures, 7 dropouts). A total of 490 participants entered the diagnostic imaging phase, of them 478 participants were treated and entered the follow-up phase.

Participant milestones

Measure	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.
Overall Study STARTED	478
Overall Study Evaluated for Efficacy	389
Overall Study COMPLETED	458
Overall Study NOT COMPLETED	20

Reasons for withdrawal

Measure	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.
Overall Study Adverse Event	8
Overall Study PCI at external hospital	1
Overall Study Assessment discrepancy	1
Overall Study CRC didn't contact participant for FU	1
Overall Study Could not get whole set of images	1
Overall Study Decline to return for GSPECT	1
Overall Study GSPECT at rest was not done	1
Overall Study Participant didn't complete MRI	1
Overall Study Uncontactable by phone	1
Overall Study Moved out of position	1
Overall Study Unable to contact	1
Overall Study Withdrawal by PI for ICA not performed	2

Baseline Characteristics

Number of female participants during baseline in SAF = 177

Baseline characteristics by cohort

Measure	Gadobutrol 0.1 mmol/kg Body Weight n=478 Participants 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.
Age, Continuous	58.6 Years STANDARD_DEVIATION 10.3 • n=478 Participants
Sex: Female, Male Female	177 Participants n=478 Participants
Sex: Female, Male Male	301 Participants n=478 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	28 Participants n=478 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	448 Participants n=478 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=478 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=478 Participants
Race (NIH/OMB) Asian	58 Participants n=478 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=478 Participants
Race (NIH/OMB) Black or African American	81 Participants n=478 Participants
Race (NIH/OMB) White	322 Participants n=478 Participants
Race (NIH/OMB) More than one race	3 Participants n=478 Participants
Race (NIH/OMB) Unknown or Not Reported	11 Participants n=478 Participants
Region of Enrollment United States	356 Participants n=478 Participants
Region of Enrollment Australia	71 Participants n=478 Participants
Region of Enrollment Singapore	31 Participants n=478 Participants
Region of Enrollment Canada	20 Participants n=478 Participants
Body weight	86.2 kilogram (kg) STANDARD_DEVIATION 18.6 • n=478 Participants
Height	170.9 centimeter (cm) STANDARD_DEVIATION 9.7 • n=478 Participants
Body mass index (BMI)	29.4 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 5.5 • n=478 Participants
Childbearing potential Yes	27 Participants n=177 Participants • Number of female participants during baseline in SAF = 177
Childbearing potential No	150 Participants n=177 Participants • Number of female participants during baseline in SAF = 177
Estimated glomerular filtration rate (eGFR)	82.0 mL/min/1.73m^2 STANDARD_DEVIATION 18.73 • n=478 Participants

PRIMARY outcome

Timeframe: 0 to 30/40 min post-injection

Population: Participants in FAS (full analysis set, included all participants who underwent pharmacologic stress and for whom eCRF entries, adequate image sets for unenhanced and gadobutrol-enhanced CMRI, and the complete image set for the SoR diagnosis were available) with significant CAD (defined as QCA stenosis of \>= 50%) as verified by SoR.

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).

Outcome measures

Measure	Gadobutrol 0.1 mmol/kg Body Weight n=150 Participants 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.
Presence of a Myocardial Perfusion Defect Indicating Significant CAD Per Participant on Gadobutrol-enhanced CMRI - Primary Analysis of Sensitivity Based on Blinded Readers' Assessment Reader 1	64.7 Sensitivity % Interval 56.5 to 72.3
Presence of a Myocardial Perfusion Defect Indicating Significant CAD Per Participant on Gadobutrol-enhanced CMRI - Primary Analysis of Sensitivity Based on Blinded Readers' Assessment Reader 2	56.0 Sensitivity % Interval 47.7 to 64.1
Presence of a Myocardial Perfusion Defect Indicating Significant CAD Per Participant on Gadobutrol-enhanced CMRI - Primary Analysis of Sensitivity Based on Blinded Readers' Assessment Reader 3	61.3 Sensitivity % Interval 53.0 to 69.2

PRIMARY outcome

Timeframe: 0 to 30/40 min post-injection

Population: Participants in FAS (included all participants who underwent pharmacologic stress and for whom eCRF entries, adequate image sets for unenhanced and gadobutrol-enhanced CMRI, and the complete image set for the SoR diagnosis were available) with significant CAD (defined as QCA stenosis of \>= 70%) as verified by SoR.

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.

Outcome measures

Measure	Gadobutrol 0.1 mmol/kg Body Weight n=105 Participants 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.
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 Reader 1	77.1 Sensitivity % Interval 67.9 to 84.8
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 Reader 2	71.4 Sensitivity % Interval 61.8 to 79.8
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 Reader 3	76.2 Sensitivity % Interval 66.9 to 84.0

PRIMARY outcome

Timeframe: 0 to 30/40 min post-injection

Population: Participants in FAS (included all participants who underwent pharmacologic stress and for whom eCRF entries, adequate image sets for unenhanced and gadobutrol-enhanced CMRI, and the complete image set for the SoR diagnosis were available) without significant CAD (defined as QCA stenosis of \>= 50%) as verified by SoR.

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).

Outcome measures

Measure	Gadobutrol 0.1 mmol/kg Body Weight n=238 Participants 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.
Absence of Myocardial Perfusion Defect Excluding Significant CAD Per Participant on Gadobutrol-enhanced CMRI - Primary Analysis of Specificity Based on Blinded Readers' Assessment Reader 1	85.3 Specificity % Interval 80.1 to 89.5
Absence of Myocardial Perfusion Defect Excluding Significant CAD Per Participant on Gadobutrol-enhanced CMRI - Primary Analysis of Specificity Based on Blinded Readers' Assessment Reader 2	88.7 Specificity % Interval 83.9 to 92.4
Absence of Myocardial Perfusion Defect Excluding Significant CAD Per Participant on Gadobutrol-enhanced CMRI - Primary Analysis of Specificity Based on Blinded Readers' Assessment Reader 3	89.5 Specificity % Interval 84.9 to 93.1

PRIMARY outcome

Timeframe: 0 to 30/40 min post-injection

Population: Participants in FAS (included all participants who underwent pharmacologic stress and for whom eCRF entries, adequate image sets for unenhanced and gadobutrol-enhanced CMRI, and the complete image set for the SoR diagnosis were available) without significant CAD (defined as QCA stenosis of \>= 70%) as verified by SoR.

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.

Outcome measures

Measure	Gadobutrol 0.1 mmol/kg Body Weight n=283 Participants 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.
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 Reader 1	82.0 Specificity % Interval 77.0 to 86.3
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 Reader 2	87.3 Specificity % Interval 82.8 to 90.9
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 Reader 3	86.9 Specificity % Interval 82.4 to 90.6

PRIMARY outcome

Timeframe: 0 to 30/40 min post-injection

Population: Participants in FAS (included all participants who underwent pharmacologic stress and for whom eCRF entries, adequate image sets for unenhanced and gadobutrol-enhanced CMRI, and the complete image set for the SoR diagnosis were available) with significant CAD (defined as QCA stenosis of \>= 50%) as verified by SoR.

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).

Outcome measures

Measure	Gadobutrol 0.1 mmol/kg Body Weight n=150 Participants 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.
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 Gadobutrol-enhanced CMRI - Reader 1	64.7 Sensitivity %
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 Gadobutrol-enhanced CMRI - Reader 2	56.0 Sensitivity %
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 Gadobutrol-enhanced CMRI - Reader 3	61.3 Sensitivity %
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 Unenhanced CMRI - Reader 1	48.0 Sensitivity %
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 Unenhanced CMRI - Reader 2	30.0 Sensitivity %
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 Unenhanced CMRI - Reader 3	29.3 Sensitivity %

PRIMARY outcome

Timeframe: 0 to 30/40 min post-injection

Population: Participants in FAS (included all participants who underwent pharmacologic stress and for whom eCRF entries, adequate image sets for unenhanced and gadobutrol-enhanced CMRI, and the complete image set for the SoR diagnosis were available) with significant CAD (defined as QCA stenosis of \>= 70%) as verified by SoR.

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.

Outcome measures

Measure	Gadobutrol 0.1 mmol/kg Body Weight n=105 Participants 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.
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 Gadobutrol-enhanced CMRI - Reader 1	77.1 Sensitivity %
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 Gadobutrol-enhanced CMRI - Reader 2	71.4 Sensitivity %
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 Gadobutrol-enhanced CMRI - Reader 3	76.2 Sensitivity %
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 Unenhanced CMRI - Reader 1	56.2 Sensitivity %
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 Unenhanced CMRI - Reader 2	35.2 Sensitivity %
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 Unenhanced CMRI - Reader 3	35.2 Sensitivity %

SECONDARY outcome

Timeframe: 0 to 30/40 min post-injection

Population: Participants in FAS (included all participants who underwent pharmacologic stress and for whom eCRF entries, adequate image sets for unenhanced and gadobutrol-enhanced CMRI, and the complete image set for the SoR diagnosis were available) with significant CAD (defined as QCA stenosis of \>= 50%) as verified by SoR.

The investigator 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%, 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).

Outcome measures

Measure	Gadobutrol 0.1 mmol/kg Body Weight n=150 Participants 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.
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 Sensitivity % Interval 64.1 to 79.0

SECONDARY outcome

Timeframe: 0 to 30/40 min post-injection

Population: Participants in FAS (included all participants who underwent pharmacologic stress and for whom eCRF entries, adequate image sets for unenhanced and gadobutrol-enhanced CMRI, and the complete image set for the SoR diagnosis were available) with significant CAD (defined as QCA stenosis of \>= 70%) as verified by SoR.

The investigator 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.

Outcome measures

Measure	Gadobutrol 0.1 mmol/kg Body Weight n=105 Participants 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.
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 Sensitivity % Interval 77.5 to 91.8

SECONDARY outcome

Timeframe: 0 to 30/40 min post-injection

Population: Participants in FAS (included all participants who underwent pharmacologic stress and for whom eCRF entries, adequate image sets for unenhanced and gadobutrol-enhanced CMRI, and the complete image set for the SoR diagnosis were available) without significant CAD (defined as QCA stenosis of \>= 50%) as verified by SoR.

The investigator 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%, 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).

Outcome measures

Measure	Gadobutrol 0.1 mmol/kg Body Weight n=239 Participants 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.
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 Specificity % Interval 80.7 to 89.9

SECONDARY outcome

Timeframe: 0 to 30/40 min post-injection

Population: Participants in FAS (included all participants who underwent pharmacologic stress and for whom eCRF entries, adequate image sets for unenhanced and gadobutrol-enhanced CMRI, and the complete image set for the SoR diagnosis were available) without significant CAD (defined as QCA stenosis of \>= 70%) as verified by SoR.

The investigator 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.

Outcome measures

Measure	Gadobutrol 0.1 mmol/kg Body Weight n=284 Participants 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.
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 Specificity % Interval 76.7 to 86.0

SECONDARY outcome

Timeframe: 0 to 30/40 min post-injection

Population: Participants in FAS (included all participants who underwent pharmacologic stress and for whom eCRF entries, adequate image sets for unenhanced and gadobutrol-enhanced CMRI, and the complete image set for the SoR diagnosis were available) with significant CAD (defined as QCA stenosis of \>= 50%) as verified by SoR.

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 defined as QCA stenosis of >=50%, 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).

Outcome measures

Measure	Gadobutrol 0.1 mmol/kg Body Weight n=150 Participants 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.
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 Unenhanced CMRI	50.7 Sensitivity %
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 Gadobutrol-enhanced CMRI	72.0 Sensitivity %

SECONDARY outcome

Timeframe: 0 to 30/40 min post-injection

Population: Participants in FAS (included all participants who underwent pharmacologic stress and for whom eCRF entries, adequate image sets for unenhanced and gadobutrol-enhanced CMRI, and the complete image set for the SoR diagnosis were available) with significant CAD (defined as QCA stenosis of \>= 70%) as verified by SoR.

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 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.

Outcome measures

Measure	Gadobutrol 0.1 mmol/kg Body Weight n=105 Participants 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.
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 Gadobutrol-enhanced CMRI	85.7 Sensitivity %
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 Unenhanced CMRI	61.0 Sensitivity %

SECONDARY outcome

Timeframe: 0 to 30/40 min post-injection

Population: Participants in FAS (all participants who underwent pharmacologic stress and for whom eCRF entries, adequate image sets for unenhanced and gadobutrol-enhanced CMRI, and the complete image set for the SoR diagnosis were available) with significant CAD (defined as QCA stenosis of \>= 50%) as verified by SoR and available GSPECT.

Presence of a myocardial perfusion defect on gadobutrol-enhanced CMRI versus GSPECT (based on RPS of the 6 myocardial regions) was calculated by majority blinded reader (BR) and investigator's assessment. Significant CAD was defined as QCA stenosis of >=50%, and was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced CMRI or GSPECT verified by SoR (CA or CTA [only if disease can be unequivocally rejected]). Sensitivity= true positive/ (true positive + false negative). Blinded reading of the gadobutrol-enhanced CMRI images and GSPECT images was performed by different readers.

Outcome measures

Measure	Gadobutrol 0.1 mmol/kg Body Weight n=141 Participants 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.
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 Gadobutrol-enhanced CMRI - Majority BR	60.0 Sensitivity %
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 Gadobutrol-enhanced CMRI - Investigator	72.3 Sensitivity %
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 GSPECT - Majority BR	54.3 Sensitivity %
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 GSPECT - Investigator	72.3 Sensitivity %

SECONDARY outcome

Timeframe: 0 to 30/40 min post-injection

Population: Participants in FAS with significant CAD (defined as QCA stenosis of \>= 70%) as verified by SoR, for assessment on gadobutrol-enhanced CMRI, and available GSPECT for assessment on GSPECT.

Presence of a myocardial perfusion defect on gadobutrol-enhanced CMRI versus GSPECT (based on RPS of the 6 myocardial regions) was calculated by majority blinded reader and investigator's 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 GSPECT 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. Blinded reading of the gadobutrol-enhanced CMRI images and GSPECT images was performed by different readers.

Outcome measures

Measure	Gadobutrol 0.1 mmol/kg Body Weight n=113 Participants 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.
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 GSPECT - Majority BR	64.9 Sensitivity %
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 GSPECT - Investigator	83.0 Sensitivity %
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 Gadobutrol-enhanced CMRI - Investigator	86.7 Sensitivity %
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 Gadobutrol-enhanced CMRI - Majority BR	78.8 Sensitivity %

SECONDARY outcome

Timeframe: 0 to 30/40 min post-injection

Population: Participants in FAS (all participants who underwent pharmacologic stress and for whom eCRF entries, adequate image sets for unenhanced and gadobutrol-enhanced CMRI, and the complete image set for the SoR diagnosis were available) without significant CAD (defined as QCA stenosis of \>= 50%) as verified by SoR and available GSPECT.

Absence of a myocardial perfusion defect on gadobutrol-enhanced CMRI versus GSPECT (based on RPS of the 6 myocardial regions) was calculated by majority blinded reader and investigator's assessment. Significant CAD was defined as QCA stenosis of >=50%, and was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced CMRI or GSPECT verified by SoR (CA or CTA [only if disease can be unequivocally rejected]). Specificity= true negative/(true negative + false positive). Blinded reading of the gadobutrol-enhanced CMRI images and GSPECT images was performed by different readers.

Outcome measures

Measure	Gadobutrol 0.1 mmol/kg Body Weight n=231 Participants 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.
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 Gadobutrol-enhanced CMRI - Majority BR	92.1 Specificity %
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 Gadobutrol-enhanced CMRI - Investigator	85.3 Specificity %
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 GSPECT - Investigator	77.5 Specificity %
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 GSPECT - Majority BR	81.0 Specificity %

SECONDARY outcome

Timeframe: 0 to 30/40 min post-injection

Population: Participants in FAS with significant CAD (defined as QCA stenosis of \>= 70%) as verified by SoR, for assessment on gadobutrol-enhanced CMRI, and available GSPECT for assessment on GSPECT.

Absence of a myocardial perfusion defect on gadobutrol-enhanced CMRI versus GSPECT (based on RPS of the 6 myocardial regions) was calculated by majority blinded reader and investigator's 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 GSPECT 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. Blinded reading of the gadobutrol-enhanced CMRI images and GSPECT images was performed by different readers.

Outcome measures

Measure	Gadobutrol 0.1 mmol/kg Body Weight n=284 Participants 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.
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 Gadobutrol-enhanced CMRI - Majority blinded reader	86.6 Specificity %
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 Gadobutrol-enhanced CMRI - Investigator	81.7 Specificity %
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 GSPECT - Majority blinded reader	78.9 Specificity %
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 GSPECT - Investigator	73.6 Specificity %

SECONDARY outcome

Timeframe: 0 to 30/40 min post-injection

Population: Participants in FAS with significant CAD (defined as QCA stenosis of \>= 50%) as verified by SoR in each coronary territory.

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, majority blinded reader and the investigator.

Outcome measures

Measure	Gadobutrol 0.1 mmol/kg Body Weight n=113 Participants 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.
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 Localization to LAD territory - Reader 3	46.2 Sensitivity %
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 Localization to LAD territory - Investigator	52.9 Sensitivity %
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 Localization to RCA territory - Investigator	68.8 Sensitivity %
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 Localization to non-LAD territory - Reader 2	54.0 Sensitivity %
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 Localization to LAD territory - Reader 1	54.8 Sensitivity %
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 Localization to LAD territory - Reader 2	40.4 Sensitivity %
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 Localization to LAD territory - Majority BR	48.1 Sensitivity %
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 Localization to non-LAD territory - Reader 1	63.7 Sensitivity %
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 Localization to non-LAD territory - Reader 3	63.7 Sensitivity %
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 Localization to non-LAD territory - Majority BR	61.1 Sensitivity %
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 Localization to non-LAD territory - Investigator	67.3 Sensitivity %
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 Localization to RCA territory - Reader 1	56.3 Sensitivity %
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 Localization to RCA territory - Reader 2	56.3 Sensitivity %
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 Localization to RCA territory - Reader 3	60.0 Sensitivity %
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 Localization to LCX territory - Reader 3	53.7 Sensitivity %
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 Localization to LCX territory - Investigator	48.8 Sensitivity %
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 Localization to LCX territory - Reader 1	57.3 Sensitivity %
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 Localization to LCX territory - Reader 2	31.7 Sensitivity %

SECONDARY outcome

Timeframe: 0 to 30/40 min post-injection

Population: Participants in FAS with significant CAD (defined as QCA stenosis of \>= 50%) as verified by SoR and available GSPECT in each coronary territory, with either blinded reading or investigator reading performed.

Sensitivity was calculated coronary territory based, a coronary territory (LAD / non-LAD) 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, majority blinded reader and the investigator. Blinded reading of the gadobutrol-enhanced CMRI images and GSPECT images was performed by different readers.

Outcome measures

Measure	Gadobutrol 0.1 mmol/kg Body Weight n=106 Participants 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.
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 Localization to non-LAD territory - Reader 8	58.0 Sensitivity %
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 Localization to LAD territory - Reader 8	32.9 Sensitivity %
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 Localization to LAD territory - Reader 9	31.4 Sensitivity %
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 Localization to LAD territory - Reader 10	37.1 Sensitivity %
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 Localization to non-LAD territory - Reader 9	45.7 Sensitivity %
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 Localization to LAD territory - Majority BR	31.4 Sensitivity %
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 Localization to non-LAD territory - Reader 10	45.7 Sensitivity %
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 Localization to non-LAD territory - Majority BR	48.1 Sensitivity %
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 Localization to non-LAD territory - Investigator	64.2 Sensitivity %
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 Localization to LAD territory - Investigator	43.9 Sensitivity %

SECONDARY outcome

Timeframe: 0 to 30/40 min post-injection

Population: Participants in FAS with significant CAD (defined as QCA stenosis of \>= 70%) as verified by SoR in each coronary territory, with either blinded reading or investigator reading performed.

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 retrospective analysis.

Outcome measures

Measure	Gadobutrol 0.1 mmol/kg Body Weight n=77 Participants 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.
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 Localization to non-LAD territory - Reader 2	68.8 Sensitivity %
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 Localization to non-LAD territory - Reader 1	71.4 Sensitivity %
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 Localization to LAD territory - Reader 1	74.6 Sensitivity %
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 Localization to LAD territory - Reader 2	58.7 Sensitivity %
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 Localization to LAD territory - Reader 3	63.5 Sensitivity %
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 Localization to non-LAD territory - Reader 3	74.0 Sensitivity %
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 Localization to non-LAD territory - Investigator	81.8 Sensitivity %
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 Localization to RCA territory - Reader 1	69.5 Sensitivity %
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 Localization to RCA territory - Reader 2	71.2 Sensitivity %
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 Localization to RCA territory - Reader 3	71.2 Sensitivity %
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 Localization to RCA territory - Investigator	79.7 Sensitivity %
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 Localization to LCX territory - Reader 1	68.8 Sensitivity %
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 Localization to LCX territory - Reader 2	43.8 Sensitivity %
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 Localization to LCX territory - Reader 3	75.0 Sensitivity %
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 Localization to LCX territory - Investigator	66.7 Sensitivity %
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 Localization to LAD territory - Investigator	68.3 Sensitivity %

SECONDARY outcome

Timeframe: 0 to 30/40 min post-injection

Population: Participants in FAS without significant CAD (defined as QCA stenosis of \>= 50% by) as verified by SoR in each coronary territory, with either blinded reading or investigator reading performed.

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.

Outcome measures

Measure	Gadobutrol 0.1 mmol/kg Body Weight n=302 Participants 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.
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 Localization to LAD territory - Reader 1	89.9 Specificity %
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 Localization to LAD territory - Reader 2	92.4 Specificity %
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 Localization to LAD territory - Reader 3	92.4 Specificity %
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 Localization to LAD territory - Majority BR	92.4 Specificity %
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 Localization to LAD territory - Investigator	89.9 Specificity %
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 Localization to RCA territory - Investigator	86.1 Specificity %
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 Localization to LCX territory - Reader 1	86.3 Specificity %
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 Localization to LCX territory - Reader 2	92.3 Specificity %
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 Localization to LCX territory - Reader 3	87.3 Specificity %
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 Localization to LCX territory - Investigator	89.0 Specificity %
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 Localization to non-LAD territory - Reader 1	83.6 Specificity %
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 Localization to non-LAD territory - Reader 2	87.3 Specificity %
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 Localization to non-LAD territory - Reader 3	87.3 Specificity %
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 Localization to non-LAD territory - Majority	86.9 Specificity %
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 Localization to non-LAD territory - Investigator	84.8 Specificity %
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 Localization to RCA territory - Reader 1	84.1 Specificity %
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 Localization to RCA territory - Reader 2	86.7 Specificity %
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 Localization to RCA territory - Reader 3	86.4 Specificity %

SECONDARY outcome

Timeframe: 0 to 30/40 min post-injection

Population: Participants in FAS without significant CAD (defined as QCA stenosis of \>= 50%) as verified by SoR and available GSPECT in each coronary territory, with either blinded reading or investigator reading,

Specificity was calculated coronary territory based, a coronary territory (LAD / non-LAD) 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, majority blinded reader and the investigator. Blinded reading of the gadobutrol-enhanced CMRI images and GSPECT images was performed by different readers.

Outcome measures

Measure	Gadobutrol 0.1 mmol/kg Body Weight n=267 Participants 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.
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 Localization to LAD territory - Reader 8	88.6 Specificity %
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 Localization to LAD territory - Reader 9	89.5 Specificity %
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 Localization to LAD territory - Reader 10	90.9 Specificity %
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 Localization to LAD territory - Majority BR	91.8 Specificity %
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 Localization to LAD territory - Investigator	88.0 Specificity %
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 Localization to non-LAD territory - Reader 8	75.0 Specificity %
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 Localization to non-LAD territory - Reader 9	85.1 Specificity %
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 Localization to non-LAD territory - Reader 10	88.0 Specificity %
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 Localization to non-LAD territory - Majority BR	85.6 Specificity %
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 Localization to non-LAD territory - Investigator	81.1 Specificity %

SECONDARY outcome

Timeframe: 0 to 30/40 min post-injection

Population: Participants in FAS without significant CAD (defined as QCA stenosis of \>= 70%) as verified by SoR in each coronary territory, with either blinded reading or investigator reading.

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 retrospective analysis.

Outcome measures

Measure	Gadobutrol 0.1 mmol/kg Body Weight n=341 Participants 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.
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 Localization to LAD territory - Reader 1	86.8 Specificity %
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 Localization to LAD territory - Reader 2	91.1 Specificity %
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 Localization to LAD territory - Reader 3	89.8 Specificity %
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 Localization to LAD territory - Investigator	85.6 Specificity %
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 Localization to non-LAD territory - Reader 1	79.1 Specificity %
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 Localization to non-LAD territory - Reader 2	85.5 Specificity %
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 Localization to non-LAD territory - Reader 3	83.0 Specificity %
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 Localization to non-LAD territory - Investigator	80.8 Specificity %
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 Localization to RCA territory - Reader 1	83.0 Specificity %
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 Localization to RCA territory - Reader 2	86.0 Specificity %
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 Localization to RCA territory - Reader 3	84.5 Specificity %
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 Localization to RCA territory - Investigator	83.3 Specificity %
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 Localization to LCX territory - Reader 1	82.6 Specificity %
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 Localization to LCX territory - Reader 2	91.2 Specificity %
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 Localization to LCX territory - Reader 3	85.3 Specificity %
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 Localization to LCX territory - Investigator	86.2 Specificity %

SECONDARY outcome

Timeframe: 0 to 30/40 min post-injection

Population: Participants in FAS with significant LMS stenosis indicating significant CAD (defined as QCA stenosis of \>= 50%) as verified by SoR.

Number of participants with myocardial perfusion defects on gadobutrol-enhanced CMRI was calculated 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%).

Outcome measures

Measure	Gadobutrol 0.1 mmol/kg Body Weight n=7 Participants 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.
Detection of Myocardial Perfusion Defect(s) on Gadobutrol-enhanced CMRI in Participants With Significant LMS Stenosis - Based on Blinded Readers' and Investigator's Assessment Isolated - Reader 1	1 Participants
Detection of Myocardial Perfusion Defect(s) on Gadobutrol-enhanced CMRI in Participants With Significant LMS Stenosis - Based on Blinded Readers' and Investigator's Assessment Single vessel - Reader 1	1 Participants
Detection of Myocardial Perfusion Defect(s) on Gadobutrol-enhanced CMRI in Participants With Significant LMS Stenosis - Based on Blinded Readers' and Investigator's Assessment 2-vessel - Reader 1	2 Participants
Detection of Myocardial Perfusion Defect(s) on Gadobutrol-enhanced CMRI in Participants With Significant LMS Stenosis - Based on Blinded Readers' and Investigator's Assessment 3-vessel - Reader 1	1 Participants
Detection of Myocardial Perfusion Defect(s) on Gadobutrol-enhanced CMRI in Participants With Significant LMS Stenosis - Based on Blinded Readers' and Investigator's Assessment Isolated - Reader 2	0 Participants
Detection of Myocardial Perfusion Defect(s) on Gadobutrol-enhanced CMRI in Participants With Significant LMS Stenosis - Based on Blinded Readers' and Investigator's Assessment Single vessel - Reader 2	1 Participants
Detection of Myocardial Perfusion Defect(s) on Gadobutrol-enhanced CMRI in Participants With Significant LMS Stenosis - Based on Blinded Readers' and Investigator's Assessment 2-vessel - Reader 2	2 Participants
Detection of Myocardial Perfusion Defect(s) on Gadobutrol-enhanced CMRI in Participants With Significant LMS Stenosis - Based on Blinded Readers' and Investigator's Assessment 3-vessel - Reader 2	1 Participants
Detection of Myocardial Perfusion Defect(s) on Gadobutrol-enhanced CMRI in Participants With Significant LMS Stenosis - Based on Blinded Readers' and Investigator's Assessment Isolated - Reader 3	1 Participants
Detection of Myocardial Perfusion Defect(s) on Gadobutrol-enhanced CMRI in Participants With Significant LMS Stenosis - Based on Blinded Readers' and Investigator's Assessment Single vessel - Reader 3	1 Participants
Detection of Myocardial Perfusion Defect(s) on Gadobutrol-enhanced CMRI in Participants With Significant LMS Stenosis - Based on Blinded Readers' and Investigator's Assessment 2-vessel - Reader 3	2 Participants
Detection of Myocardial Perfusion Defect(s) on Gadobutrol-enhanced CMRI in Participants With Significant LMS Stenosis - Based on Blinded Readers' and Investigator's Assessment 3-vessel - Reader 3	1 Participants
Detection of Myocardial Perfusion Defect(s) on Gadobutrol-enhanced CMRI in Participants With Significant LMS Stenosis - Based on Blinded Readers' and Investigator's Assessment Isolated - Majority BR	1 Participants
Detection of Myocardial Perfusion Defect(s) on Gadobutrol-enhanced CMRI in Participants With Significant LMS Stenosis - Based on Blinded Readers' and Investigator's Assessment Single vessel - Majority BR	1 Participants
Detection of Myocardial Perfusion Defect(s) on Gadobutrol-enhanced CMRI in Participants With Significant LMS Stenosis - Based on Blinded Readers' and Investigator's Assessment 2-vessel - Majority BR	2 Participants
Detection of Myocardial Perfusion Defect(s) on Gadobutrol-enhanced CMRI in Participants With Significant LMS Stenosis - Based on Blinded Readers' and Investigator's Assessment 3-vessel - Majority BR	1 Participants
Detection of Myocardial Perfusion Defect(s) on Gadobutrol-enhanced CMRI in Participants With Significant LMS Stenosis - Based on Blinded Readers' and Investigator's Assessment Isolated - Investigator	2 Participants
Detection of Myocardial Perfusion Defect(s) on Gadobutrol-enhanced CMRI in Participants With Significant LMS Stenosis - Based on Blinded Readers' and Investigator's Assessment Single vessel - Investigator	1 Participants
Detection of Myocardial Perfusion Defect(s) on Gadobutrol-enhanced CMRI in Participants With Significant LMS Stenosis - Based on Blinded Readers' and Investigator's Assessment 2-vessel - Investigator	2 Participants
Detection of Myocardial Perfusion Defect(s) on Gadobutrol-enhanced CMRI in Participants With Significant LMS Stenosis - Based on Blinded Readers' and Investigator's Assessment 3-vessel - Investigator	2 Participants

SECONDARY outcome

Timeframe: 0 to 30/40 min post-injection

Population: Participants in FAS (included all participants who underwent pharmacologic stress and for whom eCRF entries, adequate image sets for unenhanced and gadobutrol-enhanced CMRI, and the complete image set for the SoR diagnosis were available) with significant CAD (defined as QCA stenosis of \>= 50%) as verified by SoR.

Sensitivity was calculated for detection of myocardial perfusion defects 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).

Outcome measures

Measure	Gadobutrol 0.1 mmol/kg Body Weight n=84 Participants 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.
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 Single-vessel - Reader 1	45.8 Sensitivity % Interval 32.7 to 59.2
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 Single-vessel - Reader 2	32.2 Sensitivity % Interval 20.6 to 45.6
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 Single-vessel - Reader 3	39.0 Sensitivity % Interval 26.5 to 52.6
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 Single-vessel - Investigator	45.8 Sensitivity % Interval 32.7 to 59.2
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 Multi-vessel - Reader 1	77.4 Sensitivity % Interval 67.0 to 85.8
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 Multi-vessel - Reader 2	72.6 Sensitivity % Interval 61.8 to 81.8
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 Multi-vessel - Reader 3	77.4 Sensitivity % Interval 67.0 to 85.8
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 Multi-vessel - Investigator	88.1 Sensitivity % Interval 79.2 to 94.1

SECONDARY outcome

Timeframe: 0 to 30/40 min post-injection

Population: Participants in FAS with single-vessel disease indicating significant CAD (defined as QCA stenosis of \>= 70%) as verified by SoR.

Sensitivity was calculated for detection of myocardial perfusion defects on gadobutrol-enhanced CMRI and GSPECT in participants with single-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 retrospective analysis. Blinded reading of the gadobutrol-enhanced CMRI images and GSPECT images was performed by different readers.

Outcome measures

Measure	Gadobutrol 0.1 mmol/kg Body Weight n=27 Participants 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.
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 Gadobutrol-enhanced CMRI - Majority BR	66.7 Sensitivity %
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 Gadobutrol-enhanced CMRI - Investigator	70.4 Sensitivity %
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 GSPECT - Majority BR	21.1 Sensitivity %
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 GSPECT - Investigator	61.5 Sensitivity %

SECONDARY outcome

Timeframe: 0 to 30/40 min post-injection

Population: Participants in FAS with multi-vessel disease indicating significant CAD (defined as QCA stenosis of \>=70%) as verified by SoR.

Sensitivity was calculated for detection of myocardial perfusion defects on gadobutrol-enhanced CMRI and GSPECT in participants with single-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 retrospective analysis. Blinded reading of the gadobutrol-enhanced CMRI images and GSPECT images was performed by different readers.

Outcome measures

Measure	Gadobutrol 0.1 mmol/kg Body Weight n=74 Participants 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.
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 Gadobutrol-enhanced CMRI - Majority BR	81.1 Sensitivity %
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 Gadobutrol-enhanced CMRI - Investigator	90.5 Sensitivity %
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 GSPECT - Majority BR	77.6 Sensitivity %
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 GSPECT - Investigator	89.9 Sensitivity %

SECONDARY outcome

Timeframe: 0 to 30/40 min post-injection

Population: FAS

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.

Outcome measures

Measure	Gadobutrol 0.1 mmol/kg Body Weight n=389 Participants 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.
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 Gadobutrol-enhanced CMRI - Reader 1 · Confident	310 Participants
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 Gadobutrol-enhanced CMRI - Reader 1 · Somewhat confident	74 Participants
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 Gadobutrol-enhanced CMRI - Reader 1 · Not confident	4 Participants
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 Gadobutrol-enhanced CMRI - Reader 1 · Missing	1 Participants
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 Gadobutrol-enhanced CMRI - Reader 2 · Confident	300 Participants
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 Gadobutrol-enhanced CMRI - Reader 2 · Somewhat confident	71 Participants
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 Gadobutrol-enhanced CMRI - Reader 2 · Not confident	17 Participants
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 Gadobutrol-enhanced CMRI - Reader 2 · Missing	1 Participants
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 Gadobutrol-enhanced CMRI - Reader 3 · Confident	186 Participants
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 Gadobutrol-enhanced CMRI - Reader 3 · Somewhat confident	155 Participants
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 Gadobutrol-enhanced CMRI - Reader 3 · Not confident	47 Participants
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 Gadobutrol-enhanced CMRI - Reader 3 · Missing	1 Participants
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 Gadobutrol-enhanced CMRI - Investigator · Confident	274 Participants
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 Gadobutrol-enhanced CMRI - Investigator · Somewhat confident	98 Participants
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 Gadobutrol-enhanced CMRI - Investigator · Not confident	17 Participants
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 Gadobutrol-enhanced CMRI - Investigator · Missing	0 Participants
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 Unenhanced CMRI - Reader 1 · Confident	315 Participants
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 Unenhanced CMRI - Reader 1 · Somewhat confident	72 Participants
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 Unenhanced CMRI - Reader 1 · Not confident	1 Participants
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 Unenhanced CMRI - Reader 1 · Missing	1 Participants
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 Unenhanced CMRI - Reader 2 · Confident	290 Participants
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 Unenhanced CMRI - Reader 2 · Somewhat confident	84 Participants
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 Unenhanced CMRI - Reader 2 · Not confident	14 Participants
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 Unenhanced CMRI - Reader 2 · Missing	1 Participants
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 Unenhanced CMRI - Reader 3 · Confident	329 Participants
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 Unenhanced CMRI - Reader 3 · Somewhat confident	44 Participants
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 Unenhanced CMRI - Reader 3 · Not confident	15 Participants
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 Unenhanced CMRI - Reader 3 · Missing	1 Participants
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 Unenhanced CMRI - Investigator · Confident	341 Participants
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 Unenhanced CMRI - Investigator · Somewhat confident	46 Participants
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 Unenhanced CMRI - Investigator · Not confident	2 Participants
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 Unenhanced CMRI - Investigator · Missing	0 Participants

Adverse Events

Gadobutrol 0.1 mmol/kg Body Weight

Serious events: 4 serious events

Other events: 79 other events

Deaths: 0 deaths

Serious adverse events

Measure	Gadobutrol 0.1 mmol/kg Body Weight n=478 participants at risk Participants received gadobutrol at the total approved standard dose of 0.1 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.
Cardiac disorders Acute myocardial infarction	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Cardiac disorders Cardiomyopathy	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
General disorders Chest pain	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Immune system disorders Anaphylactic reaction	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Nervous system disorders Seizure	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up

Other adverse events

Measure	Gadobutrol 0.1 mmol/kg Body Weight n=478 participants at risk Participants received gadobutrol at the total approved standard dose of 0.1 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.
Cardiac disorders Angina pectoris	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Cardiac disorders Bradycardia	0.42% 2/478 • Number of events 2 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Cardiac disorders Palpitations	0.42% 2/478 • Number of events 2 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Cardiac disorders Supraventricular tachycardia	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Cardiac disorders Tachycardia	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Eye disorders Eye swelling	0.42% 2/478 • Number of events 2 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Gastrointestinal disorders Abdominal discomfort	0.63% 3/478 • Number of events 3 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Gastrointestinal disorders Abdominal pain upper	0.63% 3/478 • Number of events 3 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Gastrointestinal disorders Diarrhoea	0.63% 3/478 • Number of events 4 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Gastrointestinal disorders Flatulence	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Gastrointestinal disorders Nausea	2.7% 13/478 • Number of events 14 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Gastrointestinal disorders Tongue ulceration	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Gastrointestinal disorders Vomiting	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
General disorders Application site pruritus	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
General disorders Application site rash	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
General disorders Asthenia	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
General disorders Chest discomfort	2.1% 10/478 • Number of events 10 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
General disorders Chest pain	1.0% 5/478 • Number of events 5 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
General disorders Chills	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
General disorders Fatigue	0.63% 3/478 • Number of events 3 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
General disorders Feeling cold	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
General disorders Feeling hot	0.42% 2/478 • Number of events 2 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
General disorders Feeling jittery	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
General disorders Influenza like illness	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
General disorders Non-cardiac chest pain	0.42% 2/478 • Number of events 2 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
General disorders Infusion site extravasation	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Musculoskeletal and connective tissue disorders Arthralgia	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Musculoskeletal and connective tissue disorders Back pain	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Musculoskeletal and connective tissue disorders Myalgia	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Musculoskeletal and connective tissue disorders Neck pain	0.42% 2/478 • Number of events 2 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Musculoskeletal and connective tissue disorders Limb discomfort	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Nervous system disorders Dizziness	0.84% 4/478 • Number of events 4 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Nervous system disorders Dysgeusia	1.3% 6/478 • Number of events 6 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Nervous system disorders Head discomfort	0.42% 2/478 • Number of events 2 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Nervous system disorders Headache	5.2% 25/478 • Number of events 27 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Nervous system disorders Hypoaesthesia	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Nervous system disorders Lethargy	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Nervous system disorders Migraine	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Nervous system disorders Paraesthesia	0.42% 2/478 • Number of events 3 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Psychiatric disorders Insomnia	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.9% 9/478 • Number of events 9 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Respiratory, thoracic and mediastinal disorders Pharyngeal oedema	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Respiratory, thoracic and mediastinal disorders Throat tightness	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Skin and subcutaneous tissue disorders Urticaria	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up
Vascular disorders Flushing	0.21% 1/478 • Number of events 1 • From the time of gadobutrol injection until 24 ± 6 hours follow-up

Additional Information

Therapeutic Area Head

Bayer

Phone: (+) 1-888-8422937

Email: clinical-trials-contact@bayer.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60