Clinical Trial Results:
Multicenter open-label study to evaluate efficacy of gadobutrol-enhanced cardiac magnetic resonance imaging (CMRI) for detection of significant coronary artery disease (CAD) in subjects with known or suspected CAD by a blinded image analysis
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Summary
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EudraCT number |
2012-002563-10 |
Trial protocol |
DE GB FR |
Global end of trial date |
31 Aug 2017
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Results information
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Results version number |
v2(current) |
This version publication date |
04 May 2018
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First version publication date |
24 Mar 2018
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
BAY86-4875 / 15961
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01890421 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Bayer AG
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Sponsor organisation address |
Kaiser-Wilhelm-Allee, D-51368 Leverkusen, Germany,
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Public contact |
Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com
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Scientific contact |
Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
10 Apr 2015
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Aug 2017
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objectives (assessed by 3 study-independent blinded readers and all 3 endpoints simultaneously confirmed by the same 2 out of the 3 readers) were to:
1) Demonstrate that subject-based sensitivity of gadobutrol-enhanced cardiac magnetic resonance imaging (CMRI) at vasodilator stress/rest (lower bound of 95% confidence interval [CI]) exceeds the predefined minimum performance threshold of 60%
2) Demonstrate that subject-based specificity of gadobutrol-enhanced CMRI at vasodilator stress/rest (lower bound of 95% CI) exceeds the predefined minimum performance threshold of 55%
3) Demonstrate subject-based superior sensitivity of gadobutrol-enhanced CMRI over unenhanced wall motion CMRI.
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Protection of trial subjects |
The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization guideline E6: Good Clinical Practice. Before entering the study, the informed consent form was read by and explained to all subjects. Participating subjects signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
19 Jul 2013
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 210
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Country: Number of subjects enrolled |
Korea, Democratic People's Republic of: 108
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Country: Number of subjects enrolled |
Switzerland: 44
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Country: Number of subjects enrolled |
United States: 31
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Country: Number of subjects enrolled |
United Kingdom: 28
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Country: Number of subjects enrolled |
France: 4
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Country: Number of subjects enrolled |
New Zealand: 1
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Worldwide total number of subjects |
426
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EEA total number of subjects |
242
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
292
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From 65 to 84 years |
134
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted at 23 study centers in 7 countries (Germany, South Korea, United Kingdom, France, United States, New Zealand and Switzerland), between 19 July 2013 (first subject first visit) and 10 April 2015 (last subject last visit). | ||||||||||||
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Pre-assignment
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Screening details |
Overall, 456 subjects signed the informed consent, of them 19 did not finish their baseline visit (6 screening failure, 13 dropped out), 1 discontinued the study due to an AE. A total of 436 subjects entered the diagnostic imaging phase, of them 426 were treated with gadobutrol and entered the follow-up phase. | ||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||
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Arms
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Arm title
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Gadobutrol 0.1 mmol/kg body weight | ||||||||||||
Arm description |
Subjects 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. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Gadobutrol
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Investigational medicinal product code |
BAY86-4875
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Intravenous bolus use
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Dosage and administration details |
Subjects 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.
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Baseline characteristics reporting groups
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Reporting group title |
Gadobutrol 0.1 mmol/kg body weight
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Reporting group description |
Subjects 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Gadobutrol 0.1 mmol/kg body weight
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Reporting group description |
Subjects 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. | ||
Subject analysis set title |
Full analysis set (FAS)
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
FAS (n=376) included all participants who underwent pharmacologic stress and for whom electronic case report form (eCRF) entries, adequate image sets for unenhanced and gadobutrol-enhanced cardiac magnetic resonance imaging (CMRI), and the complete image set for the standard of reference (SoR) diagnosis were available.
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End point title |
Presence of a Myocardial Perfusion Defect Indicating Significant CAD per Subject on Gadobutrol-enhanced CMRI (Based on RPS) – Primary Analysis of Sensitivity Based on Blinded Readers' Assessment [1] | ||||||||||||||
End point description |
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). Sensitivity= true positive/ (true positive + false negative).
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End point type |
Primary
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End point timeframe |
0 to 30/40 minute (min) post-injection
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were done, no inferential statistical analyses were performed. |
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| Notes [2] - FAS with evaluable subjects for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Presence of a Myocardial Perfusion Defect Indicating Significant CAD per Subject on Gadobutrol-enhanced CMRI (Based on RPS) – Additional Secondary analysis of Sensitivity Based on the Blinded Readers' Assessment [3] | ||||||||||||||
End point description |
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 >=70% for secondary analysis, and was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced cardiac magnetic resonance imaging (CMRI) verified by standard of reference (SoR). Sensitivity= true positive/ (true positive + false negative). This additional secondary analysis of sensitivity was prospective analysis.
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End point type |
Primary
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End point timeframe |
0 to 30/40 min post-injection
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were done, no inferential statistical analyses were performed. |
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| Notes [4] - FAS with evaluable subjects for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Absence of a Myocardial Perfusion Defect Excluding Significant CAD per Subject on Gadobutrol-enhanced CMRI (Based on RPS) – Primary Analysis of Specificity Based on the Blinded Readers' Assessment [5] | ||||||||||||||
End point description |
Blinded readers evaluated 6 myocardial regions based on regional perfusion score (RPS), 0=normal; 1=abnormal, reversible perfusion defect (stress); 2=abnormal, mixed perfusion defect (reversible and fixed/permanent components); 3=abnormal, fixed/permanent perfusion defect/scar (stress and rest)]. A myocardial region a perfusion defect in case of a RPS of >=1 and was rated to have normal perfusion in case of a RPS of 0. Significant CAD was defined as quantitative coronary angiography (QCA) stenosis of >=50% for primary analysis, and was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced cardiac magnetic resonance imaging (CMRI) verified by standard of reference (SoR). Specificity= true negative/ (true negative + false positive).
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End point type |
Primary
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End point timeframe |
0 to 30/40 min post-injection
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were done, no inferential statistical analyses were performed. |
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| Notes [6] - FAS with evaluable subjects for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Absence of a Myocardial Perfusion Defect Excluding Significant CAD per Subject on Gadobutrol-enhanced CMRI (Based on RPS) – Additional Secondary Analysis of Specificity Based on the Blinded Readers' Assessment [7] | ||||||||||||||
End point description |
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 >=70% for primary analysis, and was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced cardiac magnetic resonance imaging (CMRI) verified by standard of reference (SoR). Specificity= true negative/ (true negative + false positive). This additional secondary analysis of specificity was prospective analysis.
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End point type |
Primary
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End point timeframe |
0 to 30/40 min post-injection
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| Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were done, no inferential statistical analyses were performed. |
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| Notes [8] - FAS with evaluable subjects for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Presence of a Myocardial Perfusion Defect Indicating Significant CAD per Subject on Gadobutrol-enhanced CMRI Versus Unenhanced Wall Motion CMRI Images – Primary Analysis of Sensitivity Comparison Based on the Blinded Readers' Assessment [9] | ||||||||||||||||||||
End point description |
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 quantitative coronary angiography (QCA) stenosis of >=50% for primary analysis, and was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced cardiac magnetic resonance imaging (CMRI) verified by standard of reference (SoR). Sensitivity= true positive/ (true positive + false negative).
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End point type |
Primary
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End point timeframe |
0 to 30/40 min post-injection
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| Notes [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: EudraCT database does not allow to report only one treatment group in statistical analyses section. Due to this format constraint, charts have been uploaded with the accurate details of statistical analyses for this endpoint. Please find the statistical analyses in the attachment below. |
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Attachments |
Untitled (Filename: 15961_Primary Outcome 5.pdf) |
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| Notes [10] - FAS with evaluable subjects for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Presence of a Myocardial Perfusion Defect Indicating Significant CAD per Subject on Gadobutrol-enhanced CMRI Versus Unenhanced Wall Motion CMRI Images – Additional Secondary Analysis of Sensitivity Comparison Based on the Blinded Readers' Assessment [11] | ||||||||||||||||||||
End point description |
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 quantitative coronary angiography (QCA) stenosis of >=70% for primary analysis, and was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced cardiac magnetic resonance imaging (CMRI) verified by standard of reference (SoR). Sensitivity= true positive/ (true positive + false negative). This additional secondary analysis of sensitivity was prospective analysis.
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End point type |
Primary
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End point timeframe |
0 to 30/40 min post-injection
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| Notes [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: EudraCT database does not allow to report only one treatment group in statistical analyses section. Due to this format constraint, charts have been uploaded with the accurate details of statistical analyses for this endpoint. Please find the statistical analyses in the attachment below. |
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Attachments |
Untitled (Filename: 15961_Primary Outcome 6.pdf) |
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| Notes [12] - FAS with evaluable subjects for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Presence of a Myocardial Perfusion Defect Indicating Significant CAD per Subject on Gadobutrol-enhanced CMRI – Secondary Analysis of Sensitivity Based on Investigator's Assessment | ||||||||
End point description |
Presence of a myocardial perfusion defect on gadobutrol-enhanced CMRI versus the presence of wall motion abnormalities on unenhanced CMRI images (based on regional perfusion/regional wall motion score of the 6 myocardial regions) was calculated by investigator's assessment. Significant CAD was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced CMRI or the presence of wall motion abnormalities on unenhanced CMRI images verified by SoR (significant CAD defined as QCA stenosis of >=50%). Sensitivity= true positive/ (true positive + false negative).
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End point type |
Secondary
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End point timeframe |
0 to 30/40 min post-injection
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| Notes [13] - FAS with evaluable subjects for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Presence of a Myocardial Perfusion Defect Indicating Significant CAD per Subject on Gadobutrol-enhanced CMRI – Additional Secondary Analysis of Sensitivity Comparison Based on Investigator's Assessment | ||||||||
End point description |
Presence of a myocardial perfusion defect on gadobutrol-enhanced CMRI versus the presence of wall motion abnormalities on unenhanced CMRI images (based on regional perfusion/regional wall motion score of the 6 myocardial regions) was calculated by investigator's assessment. Significant CAD was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced CMRI or the presence of wall motion abnormalities on unenhanced CMRI images verified by SoR (significant CAD defined as QCA stenosis of >=70%). Sensitivity= true positive/ (true positive + false negative). This additional secondary analysis of sensitivity was prospective analysis.
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End point type |
Secondary
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End point timeframe |
0 to 30/40 min post-injection
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| Notes [14] - FAS with evaluable subjects for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Absence of a Myocardial Perfusion Defect Excluding Significant CAD per Subject on Gadobutrol-enhanced CMRI – Secondary Analysis of Specificity Based on Investigator's Assessment | ||||||||
End point description |
Investigator’s assessment evaluated 6 myocardial regions based on regional perfusion score (RPS), 0=normal; 1=abnormal, reversible perfusion defect (stress); 2=abnormal, mixed perfusion defect (reversible and fixed/permanent components); 3=abnormal, fixed/permanent perfusion defect/scar (stress and rest). A myocardial region was rated to have a perfusion defect in case of a RPS of >=1 and was rated to have normal perfusion in case of a RPS of 0. The investigator’s assessment of subject-based specificity of gadobutrol-enhanced CMRI was analyzed with significant CAD defined as maximum stenosis severity of >=50% by QCA, which were secondary analysis. Specificity= true negative/ (true negative + false positive).
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End point type |
Secondary
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End point timeframe |
0 to 30/40 min post-injection
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| Notes [15] - FAS with evaluable subjects for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Absence of a Myocardial Perfusion Defect Excluding Significant CAD per Subject on Gadobutrol-enhanced CMRI – Additional Secondary Analysis of Specificity Based on Investigator's Assessment | ||||||||
End point description |
Investigator’s assessment evaluated 6 myocardial regions based on regional perfusion score (RPS), 0=normal; 1=abnormal, reversible perfusion defect (stress); 2=abnormal, mixed perfusion defect (reversible and fixed/permanent components); 3=abnormal, fixed/permanent perfusion defect/scar (stress and rest). A myocardial region was rated to have a perfusion defect in case of a RPS of >=1 and was rated to have normal perfusion in case of a RPS of 0. The investigator’s assessment of subject-based specificity of gadobutrol-enhanced CMRI was analyzed with significant CAD defined as maximum stenosis severity of >=70% by QCA, which were secondary analysis. Specificity= true negative/ (true negative + false positive). This additional secondary analysis of specificity was prospective analysis.
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End point type |
Secondary
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End point timeframe |
0 to 30/40 min post-injection
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| Notes [16] - FAS with evaluable subjects for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Presence of a Myocardial Perfusion Defect Indicating Significant CAD per Subject on Gadobutrol-enhanced CMRI Versus Unenhanced Wall Motion CMRI Images – Secondary Analysis of Sensitivity Comparison Based on Investigator's Assessment | ||||||||||||
End point description |
Investigator’s assessment evaluated 6 myocardial regions based on regional perfusion score (RPS), 0=normal; 1=abnormal, reversible perfusion defect (stress); 2=abnormal, mixed perfusion defect (reversible and fixed/permanent components); 3=abnormal, fixed/permanent perfusion defect/scar (stress and rest). A myocardial region was rated to have a perfusion defect in case of a RPS of >=1 and was rated to have normal perfusion in case of a RPS of 0. The investigator’s assessment of subject-based sensitivity and specificity of gadobutrol-enhanced CMRI was analyzed with significant CAD defined as maximum stenosis severity of >=50% by QCA, which were secondary analysis. Sensitivity= true positive/ (true positive + false negative).
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End point type |
Secondary
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End point timeframe |
0 to 30/40 min post-injection
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Attachments |
Untitled (Filename: 15961_Secondary Outcome 11.pdf) |
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| Notes [17] - FAS with evaluable subjects for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Presence of a Myocardial Perfusion Defect Indicating Significant CAD per Subject on Gadobutrol-enhanced CMRI Versus Unenhanced Wall Motion CMRI Images – Additional Secondary Analysis of Sensitivity Comparison Based on Investigator's Assessment | ||||||||||||
End point description |
Investigator’s assessment evaluated 6 myocardial regions based on regional perfusion score (RPS), 0=normal; 1=abnormal, reversible perfusion defect (stress); 2=abnormal, mixed perfusion defect (reversible and fixed/permanent components); 3=abnormal, fixed/permanent perfusion defect/scar (stress and rest). A myocardial region was rated to have a perfusion defect in case of a RPS of >=1 and was rated to have normal perfusion in case of a RPS of 0. The investigator’s assessment of subject-based sensitivity and specificity of gadobutrol-enhanced CMRI was analyzed with significant CAD defined as maximum stenosis severity of >=70% by QCA, which were secondary analysis. Sensitivity= true positive/ (true positive + false negative). This additional secondary analysis of sensitivity was prospective analysis.
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End point type |
Secondary
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End point timeframe |
0 to 30/40 min post-injection
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| Notes [18] - FAS with evaluable subjects for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Localization of a Myocardial Perfusion Defect to a Coronary Territory on Gadobutrol-Enhanced CMRI – Secondary Analysis of Sensitivity Based on Blinded Readers' and Investigator's Assessments | ||||||||||||||||||||||||||||||||||||||||
End point description |
Sensitivity was calculated coronary territory based, a coronary territory (left anterior descending artery [LAD] / non-LAD / right coronary artery [RCA] / left circumflex artery [LCX]) was rated positive for significant CAD (significant CAD defined as QCA stenosis of>=50%), if >=1 myocardial region within the same coronary territory showed a myocardial perfusion defect with a RPS of >=1. A coronary territory(LAD / non-LAD) was rated negative for significant CAD, if no myocardial region within the respective coronary territory showed a myocardial perfusion defect (RPS 0). Sensitivity was displayed for all 3 blinded readers and the investigator.
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End point type |
Secondary
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End point timeframe |
0 to 30/40 min post-injection
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| Notes [19] - FAS with evaluable subjects for this endpoint. |
|||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
End point title |
Localization of a Myocardial Perfusion Defect to a Coronary Territory on Gadobutrol-enhanced CMRI – Additional Secondary Analysis of Sensitivity Based on Blinded Readers' and Investigator's Assessments | ||||||||||||||||||||||||||||||||||||||||
End point description |
Sensitivity was calculated coronary territory based, a coronary territory (LAD / non-LAD / RCA / LCX) was rated positive for significant CAD (significant CAD defined as QCA stenosis of >=70%), if >=1 myocardial region within the same coronary territory showed a myocardial perfusion defect with a RPS of >=1. A coronary territory (LAD / non-LAD) was rated negative for significant CAD, if no myocardial region within the respective coronary territory showed a myocardial perfusion defect (RPS 0). Sensitivity was displayed for all 3 blinded readers and the investigator. This additional secondary analysis of sensitivity was prospective analysis.
|
||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||
End point timeframe |
0 to 30/40 min post-injection
|
||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
| Notes [20] - FAS with evaluable subjects for this endpoint. |
|||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
End point title |
Localization of a Myocardial Perfusion Defect to a Coronary Territory on Gadobutrol-enhanced CMRI – Secondary Analysis of Specificity Based on Blinded Readers' and Investigator's Assessments | ||||||||||||||||||||||||||||||||||||||||
End point description |
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.
|
||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||
End point timeframe |
0 to 30/40 min post-injection
|
||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
| Notes [21] - FAS with evaluable subjects for this endpoint. |
|||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
End point title |
Localization of a Myocardial Perfusion Defect to a Coronary Territory on Gadobutrol-enhanced CMRI – Additional Secondary Analysis of Specificity Based on Blinded Readers' and Investigator's Assessments | ||||||||||||||||||||||||||||||||||||||||
End point description |
Specificity was calculated coronary territory based, a coronary territory (LAD / non-LAD / RCA / LCX) was rated positive for significant CAD (significant CAD defined as QCA stenosis of >=70%), if >=1 myocardial region within the same coronary territory showed a myocardial perfusion defect with a RPS of >=1. A coronary territory (LAD / non-LAD) was rated negative for significant CAD, if no myocardial region within the respective coronary territory showed a myocardial perfusion defect (RPS 0). Specificity was displayed for all 3 blinded readers and the investigator. This additional secondary analysis of specificity was prospective analysis.
|
||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||
End point timeframe |
0 to 30/40 min post-injection
|
||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
| Notes [22] - FAS with evaluable subjects for this endpoint. |
|||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||
End point title |
Detection of Myocardial Perfusion Defect(s) on Gadobutrol-enhanced CMRI in Subject with Significant LMS Stenosis – Based on Blinded Readers' and Investigator's Assessments | ||||||||||||||||||||||||||||||||||||||
End point description |
Sensitivity was calculated for detection of myocardial perfusion defects on gadobutrol-enhanced CMRI in subjects 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, subjects will be rated positive for significant CAD (significant CAD defined as QCA stenosis of >=50%). Sensitivity= true positive/ (true positive + false negative).
|
||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||
End point timeframe |
0 to 30/40 min post-injection
|
||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||
| Notes [23] - FAS with evaluable subjects for this endpoint. |
|||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Presence/Absence of a MPD Indicating/Excluding Significant CAD in Subjects With Multi Versus Single Vessel Disease Evaluated on Gadobutrol-enhanced CMRI-Secondary Analysis of Sensitivity Based on Blinded Readers' and Investigator's Assessments | ||||||||||||||||||||||||
End point description |
Sensitivity was calculated for detection of myocardial perfusion defects (MPD) on gadobutrol-enhanced CMRI in subjects with single and multi-vessel diseases. If >=1 myocardial region showed a myocardial perfusion defect with a RPS of >=1, subjects will be rated positive for significant CAD (significant CAD defined as QCA stenosis of >=50%). Sensitivity= true positive/ (true positive + false negative).
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
0 to 30/40 min post-injection
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| Notes [24] - FAS with evaluable subjects for this endpoint. |
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Presence/Absence of a MPD Indicating/Excluding Significant CAD in Subjects With Multi Vs Single Vessel Disease Evaluated on Gadobutrol-enhanced CMRI-Additional Secondary Analysis of Sensitivity Based on Blinded Readers' and Investigator's Assessments | ||||||||||||||||||||||||
End point description |
Sensitivity was calculated for detection of MPD on gadobutrol-enhanced CMRI in subjects with single and multi-vessel diseases. If >=1 myocardial region showed a myocardial perfusion defect with a RPS of >=1, subjects will be rated positive for significant CAD (significant CAD defined as QCA stenosis of >=70%). Sensitivity= true positive/ (true positive + false negative). This additional secondary analysis of sensitivity was prospective analysis.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
0 to 30/40 min post-injection
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| Notes [25] - FAS with evaluable subjects for this endpoint. |
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Subjects by Their Lowest Confidence in Diagnosis Obtained on Gadobutrol-enhanced CMRI and Unenhanced Wall Motion CMRI – Based on Blinded Readers' and Investigator's Assessments | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
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 subject was displayed. All these analyses were done separately for gadobutrol-enhanced CMRI and unenhanced wall motion CMRI.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
0 to 30/40 min post-injection
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [26] - FAS with evaluable subjects for this endpoint. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From the time of gadobutrol injection until 24 ± 6 hours follow-up
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Gadobutrol 0.1 mmol/kg body weight
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
