DEF-315 Better Accuracy in Ejection Fraction (EF) Assessment With DEFINITY

Study Overview
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Brief Summary
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This is a Phase 3, prospective, open-label, multicenter study to evaluate Left Ventricular Ejection Fraction (LVEF) measurement accuracy and reproducibility of DEFINITY® contrast-enhanced and unenhanced echocardiography as compared with non-contrast cardiac magnetic resonance imaging (CMR) used as the truth standard.

Official Title
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A Phase III, Open-Label, Multicenter Trial to Evaluate Ejection Fraction, End-Diastolic and End-Systolic Volumes, by Unenhanced and DEFINITY®-Enhanced 2D-Echo and Magnetic Resonance Imaging

Conditions
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Cardiac Disease

Intervention / Treatment
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* Drug: DEFINITY®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women ≥ 18 years of age in sinus rhythm Able to communicate effectively with trial personnel LVEF measurements obtained via 2D Echo with or without contrast obtained within 6 months prior to enrollment (Day 0) Has provided signed informed consent after receiving a verbal and written explanation of this clinical trial Exclusion Criteria: Female subjects who are pregnant or lactating. All women of child bearing potential [WOCBP] must have a negative urine pregnancy test at screening regardless of contraceptive use history. Women of child-bearing potential are excluded unless they: are post-menopausal defined as amenorrhea ≥ 12 consecutive months, OR have undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy), OR have been using an adequate and medically approved method of contraception to avoid pregnancy for at least 1 month prior to DEFINITY® dose administration and be willing to continue using the same method for the duration of the study. Current illness or pathology that would prevent undergoing investigational product administration due to a significant safety risk to the patient. Uncontrolled arterial hypertension (defined as systolic blood pressure ≥ 200 mmHg or diastolic blood pressure ≥ 110 mmHg) or arterial hypotension (defined as systolic blood pressure ≤ 90 mmHg). Unstable cardiovascular status defined as: myocardial infarction or unstable angina pectoris within 6 months prior to enrollment/DEFINITY® dose administration day transient ischemic attack or stroke within 3 months prior to DEFINITY® dose administration symptomatic valvular heart disease or moderate to severe stenotic valvular heart disease clinically significant congenital heart defects current uncontrolled cardiac arrhythmias causing symptoms or hemodynamic compromise acute pulmonary embolus or pulmonary infarction acute myocarditis or pericarditis acute aortic dissection atrial fibrillation any major surgery within 4 weeks prior to screening known contraindications to undergoing CMR (e.g. implanted pacemakers, cardioverter, defibrillators) or claustrophobia participation in any investigational drug, device, or placebo study within 30 days prior to screening known hypersensitivity to perflutren, or any of the excipients in DEFINITY® prisoners or those who are subject to compulsory detention or involuntary incarceration for treatment of either a psychiatric or physical illness (e.g., infectious disease).

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: DEFINITY®<br>Each patient will undergo an unenhanced ultrasound examination and a DEFINITY® contrast-enhanced ultrasound | Drug: DEFINITY®<br>* All subjects will receive a single dose of DEFINITY®<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Value of LVEF Percentage Differences From CMR by Blinded Reader | Demonstrate improvement in accuracy in left ventricular ejection fraction (LVEF) assessment using DEFINITY® contrast-enhanced over unenhanced echocardiography by comparing LVEF percentage differences from CMR measured by 3 independent blinded image readers. | Up to 30 days between day of echocardiograms and CMR imaging | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Objective 1: Absolute Value of LVEF Percentage Differences From CMR by Blinded Reader for Sub-optimal Echocardiograms | Demonstrate improvement in accuracy in left ventricular ejection fraction (LVEF) assessment using DEFINITY® contrast-enhanced over unenhanced echocardiography in subjects with suboptimal echocardiograms by comparing LVEF percentage differences from CMR measured by 3 independent blinded readers. | Up to 30 days between day of echocardiogram and CMR imaging | 
| Secondary Objective 2: Absolute Value LVEF Percentage Differences From CMR Between Blinded Readers | Demonstrate a reduction in inter-reader variability for the assessment of left ventricular ejection fraction using DEFINITY® contrast-enhanced versus unenhanced echocardiography by comparing LVEF percentage differences from CMR between 3 independent blinded readers. | Up to 30 days between day of echocardiograms and CMR imaging | 
| Secondary Objective 3: Absolute Value End-diastolic and Systolic Volume Differences From CMR Between Blinded Readers | Demonstrate a reduction in inter-reader variability for the assessment of end-diastolic/systolic volumes using DEFINITY® contrast-enhanced versus unenhanced echocardiography by comparing end-diastolic and systolic volume differences from CMR between 3 independent blinded readers. | Up to 30 days between day of echocardiogram and CMR imaging | 
| Secondary Objective 4: Absolute Value of LVEF Percentage Differences From CMR Between Readers for Sub-optimal Echocardiograms | Demonstrate a reduction in inter-reader variability for the assessment of left ventricular ejection fraction using DEFINITY® contrast-enhanced versus unenhanced echocardiography by comparing LVEF percentage differences from CMR between 3 independent blinded readers in subjects with suboptimal echocardiograms. | Up to 30 days between day of echocardiograms and CMR imaging | 
| Secondary Objective 5: Absolute Value End-diastolic and Systolic Volume Differences From CMR Between Blinded Readers for Suboptimal Echocardiograms | Demonstrate a reduction in inter-reader variability for the assessment of end-diastolic/systolic volumes using DEFINITY® contrast-enhanced versus unenhanced echocardiography by comparing end-diastolic and systolic volume differences from CMR between 3 independent blinded readers in subjects with suboptimal echocardiograms. | Up to 30 days between day of echocardiograms and CMR imaging | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Left Ventricular Ejection Fraction, DEFINITY®, Enhanced Echocardiogram, Cardiac Magnetic Resonance