Evaluation of Safety and Efficacy of Lumason/SonoVue in Subjects Undergoing Pharmacologic Stress BR1-141

Study Overview
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Brief Summary
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The purpose of this study was to assess the safety and efficacy of Lumason-enhanced dobutamine stress echo (CE-DSE) in subjects having a suboptimal left ventricular endocardial border delineation (LV EBD) at rest and who were scheduled for coronary angiography.

Detailed Description
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The study was designed to assess the safety and efficacy of Lumason at improving the visualization of the LV EBD during pharmacologic stress echocardiography examinations and for detection or exclusion of the coronary artery disease (CAD). The study population consisted of adult subjects referred for pharmacological stress echocardiography and with suboptimal image quality during unenhanced ultrasound imaging at rest who had known or suspected CAD. Subjects enrolled in the study represented subjects who could benefit most from contrast-enhanced ultrasound (CEUS) stress echocardiography.

Official Title
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A Prospective Multicenter Phase III Clinical Evaluation of the Safety and Efficacy of Lumason™/SonoVue® in Subjects Undergoing Pharmacologic Stress Echocardiography With Dobutamine for the Diagnosis of Coronary Artery Disease

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: Lumason


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provided written Informed Consent and was willing to comply with protocol requirements; Was at least 18 years of age; Had suspected or known CAD and was scheduled to undergo coronary angiography within 6 months after the LUMASON DSE. Had undergone a previous echocardiography prior to enrollment; resulting in suboptimal unenhanced images at rest, defined as ≥ 2 suboptimal adjacent segments in any apical view. Exclusion Criteria: Was a pregnant or lactating female. Excluded the possibility of pregnancy by testing on site at the institution (serum or urine βHCG) within 24 hours prior to the start of LUMASON administration(s), by surgical history (e.g., tubal ligation or hysterectomy), post menopausal with a minimum 1 year without menses; Had any known hypersensitivity to 1 or more ingredients of LUMASON (sulfur hexafluoride or to any components of LUMASON); Had any known hypersensitivity to dobutamine; Had an ongoing or recent (within the last 30 days) acute myocardial infarction; Had known right-to-left, bidirectional or transient cardiac shunt (ruled out with agitated saline study performed before administration of LUMASON); Had electrolyte (especially potassium and magnesium) abnormalities; Had unstable pulmonary and/or systemic hemodynamic conditions e.g.: decompensated or inadequately controlled congestive heart failure (NYHA Class IV); hypovolemia; uncontrolled hypertension, i.e. resting systolic blood pressure >200 mmHg or diastolic blood pressure >110 mmHg; unstable angina; acute coronary syndrome; aortic dissection; acute pericarditis, myocarditis, or endocarditis; stenosis of the main left coronary artery; hemodynamically significant outflow obstruction of the left ventricle, including hypertrophic obstructive cardiomyopathy; hemodynamically significant cardiac valvular defect; acute pulmonary embolism; Had uncontrolled cardiac arrhythmias; Had significant disturbance in conduction; Had hypertrophic subaortic stenosis; Had an acute illness (e.g., infections, hyperthyroidism, or severe anemia); Was previously entered into this study or received an investigational compound within 30 days before admission into this study; Had been treated with any other contrast agent either intravascularly or orally within 48 hours of the first LUMASON administration; Had 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 had not reached targeted heart rate with peak dobutamine infusion, subjects with the following were excluded: Glaucoma; Pyloric stenosis; Prostatic hypertrophy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lumason<br>Lumason (sulfur hexafluoride lipid-type A microspheres) 2 mL IV injection | Drug: Lumason<br>* Lumason (sulfur hexafluoride-type A microspheres) an ultrasound contrast agent was administered as 2 single 2-mL IV injections during rest and stress echocardiography<br>* Other names: SonoVue;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity and Specificity for Detection or Exclusion of Coronary Artery Disease (CAD) | The diagnostic performance of the echocardiographic images was compared to the truth standard to determine sensitivity and specificity. A diagnosis of coronary artery disease (CAD) was determined for both the echo images and truth standard (positive diagnosis for CAD is defined as >/= 50% stenosis of any vessel on coronary angiography or if no coronary angiography is performed the occurence of a cardiac event based on clinical information for up to 6 months post dose; otherwise the diagnosis is negative). Results for sensitivity and specificity are reflected based on difference between contrast enhanced stress echo and unenhanced stress echo. Results for analysis of data based on majority assessment from the three off-site blinded readers are presented. Sensitivity and specificity are the percentages of correctly diagnosed subjects by stress echo over the total positive and negative subjects according to the truth standard respectively. | Participants were followed until they had coronary angiography or up to 6 months post dose to collect clinical information on cardiac events if no coronary angiography were performed | 
| Reader-Specific Percentages of Participants Identified as Having a Critical Shift From Suboptimal to Optimal Echocardiographic Images | The percentage of subjects with suboptimal images (defined as >= 2 adjacent segments with inadequate left ventricular endocardial border delineation (LV EBD) in any of the 3 apical views) at unenhanced stress echo converted to adequate (reduction of suboptimal segments in any of the 3 apical views) at contrast-enhanced stress echo | Participants were followed until they had coronary angiography or up to 6 months post dose to collect clinical information on cardiac events if no coronary angiography was performed | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Total LV EBD | Measured as the change in the total LV EBD score based on the 17 segments, from peak stress unenhanced vs. peak stress contrast-enhanced. Total LV EBD score ranges from 0 to 34 and higher score is better outcome. | Participants were followed until they had coronary angiography or up to 6 months post dose to collect clinical information on cardiac events if no coronary angiography was performed | 
| Number of Participants With Adverse Events | To obtain safety data in subjects administered Lumason during echocardiography | up to 72 hours post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lumason, Dobutamine stress echo, stress echo, coronary artery disease