acquiring consensus for contrast echocardiography system settings - access study

Conditions: Coronary Artery Disease

Summary: this study evaluated and optimized settings for, and evaluated the performance of, ai-700-enhanced echocardiographic imaging on several ultrasound imaging platforms, as well as collected additional safety data for ai-700 in healthy volunteers and stable cardiac patients.

because the quality of ai-700-enhanced images is in part determined by the ultrasound (us) settings selection, the continuing study of different imaging modes and/or techniques is required in order to provide us settings recommendations for the many available systems. therefore ai-700-enhanced imaging was performed in this study using imaging platforms and modes not previously tested and the ai-700 dose and administration methods employed in previous phase 3 studies. two cohorts of subjects were studied at each site. enrollment commenced with cohort a and included normal (healthy) volunteers and stable cardiac patients. settings optimization was performed in cohort a using a single platform and real-time imaging. if the sponsor agreed that the images and settings acquired in cohort a were acceptable, the site was authorized to begin enrollment in cohort b using the platform and settings that were defined in cohort a. authorized sites enrolled stable cardiac patients in cohort b; no healthy volunteers were studied. for cohort b subjects, the first 0.04 ml/kg dose of ai 700 was used to evaluate real-time imaging with the settings defined in cohort a. the second dose of ai-700 for cohort b subjects may have been used to confirm the data obtained with the first dose, or to explore imaging in a second mode (e.g. 3d/4d) and/or using real-time, high mechanical index triggered imaging on a second platform.

Eligibility criteria:
inclusion criteria: * for cohort a, men and non-pregnant/non-lactating women in good health who are 18 to 70 years of age and who have a low chance of cad will be enrolled. * for cohort b, men and non-pregnant/non-lactating women in good health who are 18-70 years of age who have had a prior mi and/or coronary artery revascularization intervention \>90 days before ai-700 administration, without new or recurrent angina will be enrolled. exclusion criteria: * healthy volunteers in cohort a who have or have had any of the following conditions will be excluded from the study: clinically significant intra-cardiac shunts or any other cardiovascular structural and/or severe functional abnormalities on the qualification echo, unless deemed not clinically relevant by the investigator and subsequently approved by the sponsor; ejection fraction (ef, estimated from the qualification echo) that is ≤55% (outside normal range), history or clinical manifestations of significant mental illness or significant pulmonary, hematological, renal, hepatic, central nervous, cardiovascular, genitourinary, or gastrointestinal disorders, or diabetes; history of any major surgical procedure within 90 days of screening/baseline; body mass index (bmi) \>35; sitting systolic blood pressure \ 150 mmhg, diastolic blood pressure \ 95 mmhg, or a pulse rate \ 90 bpm; oxygen saturation \ 5/min) premature ventricular or atrial contractions (pvc, pac), and any ≥2nd av block, bundle branch block (bbb), or rhythm abnormality. * stable cardiac patients in cohorts a or b who have had any of the following conditions will be excluded from the study: any clinically unstable condition or major surgery within 30 days prior to screening/baseline (including but not limited to severe arterial hypertension, pulmonary hypertension, or any increase in pulmonary pressures due to increased pulmonary resistance, hypotension, bradycardia, tachycardia, unstable angina); cerebrovascular accident or transient ischemic attack within 90 days prior to dosing; congestive heart failure graded as new york heart association class 3 or 4 within 90 days prior to dosing; significant left main cad (≥50% stenosis); moderate to severe chronic obstructive pulmonary disease (copd) within 6 months prior to dosing; or oxygen saturation \ 5/min) pvcs or pacs, history of prolonged qt/qtc (\>500 msec), use of automatic implantable cardioverter/defibrillator, and any ≥2nd av block, bbb, or rhythm abnormality that has not been evaluated and treated by a specialist or for which current treatment is not adequately effective to the extent that subject safety is assured.

Keywords: coronary artery disease echocardiography cardiac imaging heart disease ultrasound contrast agent myocardial contrast enhancement myocardial perfusion