Abiomed Ends PROTECT II Study and Announces Interim Results

December 6, 2010—Abiomed, Inc. (Danvers, MA) announced completion of the PROTECT II study. The study termination is based on a futility determination at the planned interim analysis regarding the primary endpoint, which the company believes will be due to unanticipated confounding variables related to the use of rotational atherectomy in the study. The decision to end the study followed the recommendation of the Data Safety Monitoring Board, the company advised.

PROTECT II principal investigator William O'Neill, MD, commented, “Atherectomy was an unanticipated variable that resulted from the operators' decision to ‘do more with Impella.' Our investigators had unblinded knowledge of the treatment arm after randomization. It is interesting that operators felt that they could do more complex interventions once randomized to Impella and this in and of itself is an important finding.”

According to company, the PROTECT II study is a prospective, multicenter, randomized controlled study of the Abiomed Impella 2.5 versus intra-aortic balloon (IAB) in patients undergoing nonemergent, high-risk percutaneous coronary intervention (PCI) requiring hemodynamic support. The study's purpose is to determine the safety and effectiveness of the Impella 2.5 as compared to optimal medical management with an IAB during high-risk angioplasty. The study protocol was for low ejection fraction (EF) patients with unprotected left main (EF ≤ 35%) or triple-vessel disease (EF ≤ 30%) measured with a primary endpoint of 10 major adverse event (MAE) components, including major adverse cardiovascular or cerebrovascular events at 30 days for a total of 654 patients. The primary MAE endpoint was the prospective 30-day post-PCI occurrence of death, myocardial infarction, stroke, repeat revascularization (PCI/coronary artery bypass grafting), need for any cardiovascular operation, acute renal dysfunction, increase in aortic insufficiency, severe hypotension, cardiopulmonary resuscitation, arrhythmia requiring Trt, or failure to adequately reopen the vessel. The thesis assumed MAE rates of ≥ 20% for Impella and ≥ 30% for IAB.

Abiomed stated that for the entire study population, the Impella device significantly reduced out-of-hospital MAEs by 52% compared to IAB for the duration of the 90-day monitoring (N = 302; P = .02). There was an overall positive trend in the majority of patients (n = 267, 88%) at the interim analysis, in which Impella reduced the MAE rate by 26% over the IAB (Impella 32% vs IAB 43%; P = .11). Impella provided a 47% reduction in MAEs over IAB in a subgroup that represents 70% of the protocol study population (Impella 23% vs IAB 43%; P = .009). Dr. O'Neill will present an analysis of a PROTECT score in April at the annual American College of Cardiology scientific session in New Orleans. 



Further data showed that when using atherectomy, Impella significantly reduced repeat revascularization (P = .02). The data revealed confounding variables in the treatment between the two arms with the most significant differences related to two times more frequent use (P = .04) and two times the number of passes per use (P = .003) of rotational atherectomy in the Impella arm compared to the IAB arm, accounting for 12% (n = 38) of total PROTECT II patients at the interim. Use of atherectomy during PCI has previously been shown to increase creatine kinase-MB release after PCI, triggering an endpoint in PROTECT II.

In the overall interim study population of 305 patients at 30 days, the MAE rate was 38% for Impella versus 43% for IAB (P = .4). For patients treated without atherectomy (88%, n = 267), the 30-day MAE rate was 32% for Impella versus 43% for IAB (P = .11). For patients treated with atherectomy (12%, n = 38), the MAE rate was for 72% for Impella (n = 25) versus 46% for IAB (n = 13) (P = .12). Also in the atherectomy group, there was significantly lower repeat revascularization (P = .04) and higher creatine kinase-MB release (P = .02) in the Impella arm. There was no significant difference in death at 30 days (Impella 4% vs IAB 8%).

The company noted that these results were observed despite other significant treatment variables that were identified in the interim report. These included two times the treatment of saphenous vein graft in Impella arm (P = .04), higher contrast media in Impella arm (P = .01), 32% of IAB but only 6% of Impella patients left the catheterization laboratory with a device implanted (P < .001), and IAB patients had four times longer mean support (2 hours of Impella support vs 9 hours of IAB support; P < .001).