Abstract 2479: Accurate Detection of Coronary Artery Disease by Echocardiography using Perflubutane Polymer Microspheres, a Novel Contrast Agent: Comparison with Nuclear Perfusion Imaging in Two Phase Three Multicenter Clinical Trials
Background: RAMP (Real-time Assessment of Myocardial Perfusion Imaging)-1 and -2 are Phase 3 trials conducted to determine if perflubutane polymer microspheres (PPM) injectable suspension (formerly AI-700), a synthetic biodegradable ultrasound contrast agent, can assess myocardial perfusion and detect coronary disease in patients being evaluated for inducible ischemia.
Methods: Among RAMP-1 and -2 angina patients from 28 international sites, those who underwent PPM echocardiography (ECHO) imaging (real-time and triggered) as well as 99mTc quantitative myocardial perfusion imaging (nuclear) at rest and at dipyridamole stress comprised the efficacy population (n=662). Images were interpreted for presence of defect (wall motion and/or perfusion) by independent blinded readers (3 ECHO and 1–3 nuclear readers for each study). Disease was defined by quantitative coronary angiography (≥ 70% stenosis), if available, or 90 day outcome with clinical history and nuclear assessment. Primary efficacy endpoints (accuracy followed by sensitivity and specificity) were evaluated using non-inferiority and superiority analysis (one-sided alpha=0.025) compared to nuclear. The median performing nuclear reader was the comparator in RAMP-2.
Results: RAMP-1 and -2 consisted of 285 patients (125 (44%) disease positive) and 377 patients (220 (58%) disease positive), respectively. Compared to nuclear, 6, 4 and 3 of 6 ECHO readers were non-inferior for accuracy, sensitivity and specificity, respectively. Moreover, 2 and 3 ECHO readers also demonstrated superiority for specificity and sensitivity, respectively (Table⇓). Majority of AEs (headache, chest pain or discomfort, nausea and flushing) occurred following dipyridamole dosing, were mild, transient and required no treatment.
Conclusions: PPM ECHO imaging was well-tolerated and has similar diagnostic performance compared to nuclear perfusion in chest pain patients being evaluated for inducible ischemia.