Evaluation of Safety and Efficacy of Lumason in Pediatric Echocardiography

Study Overview
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Brief Summary
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Safety and Efficacy Study in pediatric subjects aged 9 to 17 years of age with suboptimal LV EBD on non-contrast 2D echocardiography. Imaging modalities that are used throughout the study in pediatric subjects represented those utilized in routine clinical practice in adults.

Detailed Description
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This was a Phase III, multicenter, open-label study that was to be conducted at approximately 7-12 sites in the United States, Canada and Europe in pediatric patients with suboptimal LV EBD on non-contrast 2D transthoracic echocardiography. It was estimated that 92 patients were to be enrolled to provide 73 evaluable patients. Three cardiologists unaffiliated with enrolling centers (blinded readers), blinded to the patient's identity and clinical profile were to independently evaluate the echocardiograms. The efficacy analysis was primarily based on the blinded reader evaluations. Imaging modalities that are used throughout the study in pediatric subjects represented those utilized in routine clinical practice in adults. One of the sites participating in this study was to be asked to consent a subset of patients for additional blood sampling for analysis of SF6 concentration in blood from a total of 6 patients (3 males and 3 females) in the age group 9 up to 12 years of age and 6 patients (3 males and 3 females) in the age of >12 up to and including 17 years. The current study was designed to assess the efficacy of Lumason-enhanced echocardiography in pediatric patients.

Official Title
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A Multicenter Clinical Evaluation of Safety and Efficacy of Lumason as a Contrast Agent in Pediatric Echocardiography

Conditions
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Heart Disease

Intervention / Treatment
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* Drug: sulphur hexafluoride lipid-type A microspheres


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide Written informed consent from parent(s) or legal guardian Provide assent when required according to local regulations Suspected of having cardiac disease or undergoing evaluation of cardiac anatomy for congenital heart disease Undergone a previous transthoracic echocardiogram within one month prior to enrollment resulting in suboptimal left ventricular endocardial border defined as ≥ 2 contiguous segments in any given view that cannot be visualized. Exclusion Criteria: Children < 9 years of age Previously enrolled in the study Administered any other contrast agent either intravascularly or orally within 48 hours of Lumason administration Known right-to-left, bidirectional or transient cardiac shunt (ruled out with agitated saline study performed before administration of Lumason) Known hypersensitivity to one or more of the ingredients of the investigational product Received an investigational compound within 30 days before enrolling into this study Pregnant or lactating female Determined by investigator to be unsuitable for the study

Ages Eligible for Study
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Minimum Age: 9 Years
Maximum Age: 17 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>All patients were administered, Lumason (sulphur hexafluoride lipid-type A microspheres) an ultrasound contrast agent as a single 0.03 mL/kg bolus injection during echocardiography. | Drug: sulphur hexafluoride lipid-type A microspheres<br>* Ultrasound imaging contrast agent<br>* Other names: SonoVue;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Left Ventricular Endocardial Border Delineation (LV EBD) Scores | The total LV EBD score for a subject was the total of the EBD scores (Inadequate - 0, sufficient - 1, Good - 2) from the 17 segments (from the apical 4-chamber, apical 2-chamber and apical long (3-chamber) views, according to the guidelines of the American Society of Echocardiography). The total LV EBD scores could range from 0 to 34 and are presented below for each of the three readers for both unenhanced ultrasound (UEUS) and contrast-enhanced ultrasound (CEUS). Change from baseline is the difference between UEUS and CEUS in total LV EBD scores. | Immediately post dose-Day 1 | 
| Percentage of Participants With Adequate Left Ventricular Opacification (LVO) | LVO was graded as 0 to +3, 4-point rating scale. Left ventricular opacification rating of +2 (non-homogeneous) or +3 (complete and homogeneous) was considered as adequate LVO. | Immediately post dose-Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | To obtain safety data in pediatric subjects administered Lumason for LV EBD improvement during echocardiography | Up to 72 hours post dose |