Contrast-enhanced echocardiography (echo) imaging was well-tolerated and has similar diagnostic performance compared to nuclear perfusion in chest pain patients being evaluated for inducible ischemia. The results of a multi-center Phase III trial utilizing perflubutane polymer microspheres (PPM), developed by Accusphere and marketed as Imagify, were presented by Roxy Senior, MD, from the department of cardiovascular medicine at Northwick Park Hospital in Middlesex, U.K., at the American Heart Association scientific sessions held this week in Orlando, Fla.
The Real-time Assessment of Myocardial Perfusion Imaging (RAMP)-1 and RAMP-2 were Phase 3 trials conducted to determine if Imagify, a synthetic biodegradable ultrasound contrast agent, can assess myocardial perfusion and detect coronary disease in patients being evaluated for inducible ischemia. The trials took place in 28 international sites.
As Senior explained to Health Imaging News, Imagify is a microparticle, as opposed to other contrast agents, which are microbubbles. During his presentation, Senior said that one of the aims of the trial was to assess the safety and efficacy of using the contrast agent.
For the RAMP-1 and RAMP-2 trials, 662 angina patients with a median age of 62 underwent PPM echo imaging as well as 99mTc quantitative myocardial perfusion imaging at rest and dipyridamole stress testing at rest. Images were interpreted for presence of defects in wall motion and/or perfusion by independent blinded readers. Disease was defined by quantitative coronary angiography with more than 70 percent stenosis rate, or a 90-day outcome with clinical history and nuclear assessment. The primary efficacy endpoints -- accuracy followed by sensitivity and specificity -- were evaluated using non-inferiority and superiority analysis comparing the echo results to nuclear imaging results.
RAMP-1 consisted of 285 patients, 44 percent that were disease positive, and RAMP-2 consisted of 377 patients, 58 percent of which were disease positive. 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. The majority of side effects, such as headache, chest pain or discomfort, nausea and flushing, occurred following dipyridamole dosing, and were mild and transient. Senior said that only one patient experienced hypersensivity to Imagify and the effect was minor.
Senior and his colleagues concluded that results from the nuclear testing and the contrast echo were similar, and produced very few side effects. In addition, the patients were not subjected to radiation.
After his presentation, Senior told Health Imaging News that cardiologists want to use echo contrast perfusion imaging testing and yet regulatory issues prohibit them. If they were to use this form of testing, it is considered by the FDA to be an off-label usage, and therefore the cardiologists would not receive reimbursements. Yet, during his presentation, Senior encouraged his audience to use it, because the equipment is available to most cardiologists and the results are promising.
Senior also said that he doesn’t expect Imagify to receive the same FDA black-box warning as current contrast agents on the market because it is not an iodine or heavy-metal based compound. Senior said the FDA would have to look at Imagify with a completely different category.
According to an Accusphere spokeswoman, the firm is currently preparing a New Drug Application (NDA) for the FDA, and intends to submit the NDA by early 2008. Initially, the Watertown, Mass.-based company had planned to submit by the conclusion of this year, but the spokeswoman said the developer wanted to ensure the application is completed properly.
Accusphere was the sole sponsor of the RAMP-1 and RAMP-2 trial.