Safety and Efficacy Study of PB127 Ultrasound Contrast Agent for Diagnosis of Coronary Artery Disease

Study Overview
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Brief Summary
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The purpose of this study is to determine if the use of PB127 with cardiac ultrasound assists in the diagnosis or exclusion of coronary artery disease.

Official Title
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A Phase 3 Clinical Trial to Assess Perfusion and Obstruction Identified by Non-Invasive Technology Using PB127 Ultrasound Contrast Agent in Patients With Suspected Obstructive Coronary Artery Disease II

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: PB127 for Injectable Suspension


Participation Criteria
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Eligibility Criteria
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18 years old or older and able to provide written informed consent; All subjects must be scheduled for or have undergone SPECT within 28 days prior to or following Study Day 1 Subjects with very low/low pre-test probability of coronary artery disease must consent to participate in the extension trial 127-014-A Subjects with very low/low pre-test probability of coronary artery disease must not have a current diagnosis of obstructive CAD on angiogram or prior MI Subjects with very low/low pre-test probability of coronary artery disease with a current diagnosis of obstructive CAD on angiogram or prior MI may be enrolled into Stratum 2 Subjects with intermediate or high pre-test probability of coronary artery disease must be scheduled for coronary angiography within the 28 days following Study Day 1 Sinus rhythm at the time of the study procedure Adequate visualization of myocardial segments Appropriate candidate for stress testing according to ACC/AHA Guidelines for Exercise Testing Exclusion Criteria: Women who are pregnant or lactating Known hypersensitivity or known contraindication to: Dipyridamole Ultrasound contrast agents (including PB127 and excipients) Blood, blood products, albumin, egg, or protein Use of caffeine or xanthine containing products within the 24 hours prior to Study Day 1 Previous exposure to PB127 Ultrasound Contrast Agent Major surgery within 7 days prior to Study Day 1 (requiring general anesthesia and/or overnight stay) Heart transplant or history of CABG Known hemodynamically significant or symptomatic right-to-left shunt (including shunts that are associated with prior TIAs or strokes) Recent history of sustained ventricular tachycardia Pacemaker or defibrillator Unstable cardiac status Unstable angina grade CCS Class IV severity (any physical activity causes limiting symptoms; symptoms may be present at rest in a patient with prior exertional angina) with ongoing symptoms and/or ongoing infusion of intravenous nitroglycerin Decompensated heart failure Second-degree or greater heart block, sick sinus syndrome Frequent (>60/hour) or symptomatic ventricular ectopics at baseline Hypertension (SBP >200 and/or DBP >110 mmHg on two consecutive readings within one hour of PB127 MPE) Hypotension (SBP <90 mmHg) Severe aortic stenosis (>40 mmHg mean gradient or <0.6 cm2/m2 valve area index) Pulmonary edema within the 7 days prior to Study Day 1 Resting oxygen saturation of less than 90% on room air Myocardial infarction or cerebral vascular accident / transient ischemic attack within the 28 days prior to Study Day 1 Chronic Obstructive Pulmonary Disease (COPD) or bronchospastic airway disease, which in the opinion of the Investigator, is significant enough to contraindicate dipyridamole Known history of severe pulmonary hypertension characterized by estimated pulmonary artery systolic pressure of >50 mmHg Liver disease characterized by one or more of the following Current jaundice Elevated bilirubin > upper limit of normal Currently elevated hepatic enzymes > 2X upper limit of normal Current or previous hepatic viral infection (not including hepatitis A) Chronic hepatitis Medical conditions or other circumstances that would significantly decrease the chances of obtaining reliable data or achieving the study objectives (i.e., drug dependence, psychiatric disorder, dementia, or associated illness); extenuating circumstances or medical conditions that make it unlikely that a patient can complete the clinical trial or follow up evaluations; or other reasons for expected poor compliance with the clinical investigator's instructions.

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

| Intervention/Treatment |
| --- |
|Drug: PB127 for Injectable Suspension|0.062 mg/kg continuous IV infusion (100-250 mL/hr) during echocardiography, not to exceed 60 minutes infusion, single dose.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the diagnostic performance of PB127 MPE for the detection and/or exclusion of significant obstructive coronary artery disease as defined by qualitative coronary angiography or qualifying clinical outcome |  | 72 hours, 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the diagnostic performance of PB127 MPE to SPECT for the detection and/or exclusion of significant obstructive coronary artery disease. |  | 72 hours, 6 months | 
| To assess the concordance of PB127 MPE with SPECT in the differentiation of defect type (fixed versus reversible) in patients with significant obstructive CAD. |  | 72 hours, 6 months | 
| To evaluate the diagnostic performance characteristics of PB127 MPE for identifying the location of significant obstructive CAD as defined by quantitative coronary angiography |  | 72 hours | 
| To assess the change in diagnostic certainty when PB127 MPE and relevant clinical information are combined over relevant clinical information alone. |  | 72 hours, 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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heart disease, coronary artery disease, echocardiogram, ultrasound, angiogram, SPECT, chest pain, perfusion