E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Suspected or known Coronary Artery Disease |
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E.1.1.1 | Medical condition in easily understood language |
Suspected or known Coronary Artery Disease |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10011082 |
E.1.2 | Term | Coronary artery disorders |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of SonoVue-enhanced dobutamine stress echocardiography (DSE) in subjects with suspected or known CAD having suboptimal left ventricular (LV) endocardial border delineation (EBD) at unenhanced echocardiography in terms of:
a) Sensitivity and specificity for the detection or exclusion of CAD in unenhanced versus SonoVue-enhanced DSE using coronary angiography or clinical follow-up as the truth standard;
b) Critical shift from suboptimal (≥2 adjacent segments inadequate on any apical view) at unenhanced dobutamine stress echocardiography (UE-DSE) to adequate images (reduction of suboptimal adjacent segments) for LV EBD at contrast-enhanced dobutamine stress echocardiography (CE-DSE).
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E.2.2 | Secondary objectives of the trial |
To further evaluate the following: a) Change from peak stress non-contrast ultrasound (Unenhanced-Dobutamine Stress Echocardiography) versus peak stress contrastenhanced ultrasound (Contrast Enhanced-Dobutamine Stress Echocardiography) in total Left Ventricle Endocardial Border Delineation score.
b) To obtain safety data in subjects undergoing Dobutamine Stress Echocardiography with SonoVue. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provides written Informed Consent and is willing to comply with protocol requirements; 2. Is at least 18 years of age; 3. Has suspected or known CAD and is scheduled to undergo coronary angiography within 6 months after the SonoVue DSE. 4. Has undergone a previous echocardiography prior to enrollment; resulting in suboptimal unenhanced images at rest, defined as ≥ 2 suboptimal adjacent segments in any apical view. |
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E.4 | Principal exclusion criteria |
1. A pregnant or lactating female. Exclude the possibility of pregnancy: a) by testing on site at the institution (serum or urine βHCG) within 24 hours priorto the start of SonoVue administration(s), b) by surgical history (e.g., tubal ligation or hysterectomy), c) post menopausal with a minimum 1 year without menses; 2. Has any known hypersensitivity to 1 or more ingredients of SonoVue (sulfur hexafluoride or to any components of SonoVue); 3. Has any known hypersensitivity to dobutamine; 4. Has an ongoing or recent (within the last 30 days) acute myocardial infarction; 5. Has known right-to-left, bidirectional or transient cardiac shunt (ruled out with agitated saline study performed before administration of SonoVue); 6. Has electrolyte (especially potassium and magnesium) abnormalities; 7. Has unstable pulmonary and/or systemic hemodynamic conditions e.g.: a) decompensated or inadequately controlled congestive heart failure (NYHA Class IV); b) hypovolemia; c) uncontrolled hypertension, i.e. resting systolic blood pressure >200 mmHg or diastolic blood pressure >110 mmHg; d) unstable angina; e) acute coronary syndrome; f) aortic dissection; g) acute pericarditis, h) myocarditis, or endocarditis; i) stenosis of the main left coronary artery; j)hemodynamically significant outflow obstruction of the left ventricle, including hypertrophic obstructive cardiomyopathy; k) hemodynamically significant cardiac valvular defect; l) acute pulmonary embolism; 8. Has uncontrolled cardiac arrhythmias; 9. Has significant disturbance in conduction; 10. Has hypertrophic subaortic stenosis; 11. Has an acute illness (e.g., infections, hyperthyroidism, or severe anemia); 12. Was previously entered into this study or received an investigational compound within 30 days before admission into this study; 13. Has been treated with any other contrast agent either intravascularly or orally within 48 hours of the first SonoVue administration; 14. Has any medical condition or other circumstances which would significantly decrease the chances of obtaining reliable data, achieving study objectives, or completing the study and/or postdose follow-up examinations;
In addition, due to the use of Atropine in subjects who have not reached targeted heart rate with peak dobutamine infusion, subjects with the following will be excluded: 1. Glaucoma; 2. Pyloric stenosis; 3. Prostatic hypertrophy. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Objective(s): • To assess the efficacy of SonoVue-enhanced dobutamine stress echocardiography (DSE) in subjects with suspected or known coronary artery disease (CAD) having suboptimal left ventricular (LV) endocardial border delineation (EBD) at unenhanced echocardiography in terms of: 1) Sensitivity and specificity for the detection or exclusion of CAD in unenhanced versus SonoVue-enhanced DSE using coronary angiography or clinical follow-up as the truth standard; 2) Critical shift from suboptimal (≥2 adjacent segments inadequate on any apical view) at unenhanced dobutamine stress echocardiography (UE-DSE) to adequate images (reduction of suboptimal adjacent segments) for LV EBD at contrast-enhanced dobutamine stress echocardiography (CE-DSE). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At the end of the blinded reading |
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E.5.2 | Secondary end point(s) |
Secondary Objective(s) 1) Change from peak stress non-contrast ultrasound (UE-DSE) versus peak stress contrast-enhanced ultrasound (CE-DSE) in total LV EBD score. 2) To obtain safety data in subjects undergoing DSE with SonoVue. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Change in total LV EBD scores at peak stress from UE-DSE to CE-DSE. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Canada |
Netherlands |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study is defined as the last subject’s image review conducted by the off-site blinded assessor(s). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 31 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 2 |