The Data Safety Monitoring Board has stopped Abiomed’s PROTECT II study based on a “futility determination” at the planned interim analysis regarding the primary endpoint, which the company views as likely to be due to “unanticipated confounding variables related to the use of rotational atherectomy in the study,” the company reported.
The study was designed to measure major adverse events at 30 days in high risk PCI patients randomized to receive hemodynamic support during the procedure with the Impella versus intra-aortic balloon (IAB).
“Atherectomy was an unanticipated variable which resulted from the operators’ decision to ‘do more with Impella.’ Our investigators had unblinded knowledge of the treatment arm after randomization,” said William O’Neill, MD, from the University of Miami and principal investigator of PROTECT II. “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 the Danvers, Mass.-based Abiomed, the results of PROTECT II are:
- For the entire study population, Impella significantly reduced out of hospital major adverse events (MAE) by 52 percent compared with IAB for the duration of the 90-day monitoring.
- There was an overall positive trend (88 percent) in the study’s interim analysis, in which Impella reduced the MAE rate by 26 percent over the IAB (Impella 32 percent MAE vs. IAB 43 percent MAE).
- Impella provided a 47 percent reduction in major adverse events over IAB in a subgroup that represents 70 percent of the protocol study population (Impella 23 percent MAE vs. IAB 43 percent MAE). The researchers said an analysis of a PROTECT score will be presented at the upcoming American College of Cardiology (ACC) meeting in April.
- When using atherectomy, Impella significantly reduced repeat revascularization.
- Finally, the data revealed confounding variables in the treatment between the two arms with the most significant differences related to two times more frequent use and two times the number of passes per use of rotational atherectomy in the Impella arm compared with the IAB arm, accounting for 12 percent of total PROTECT II patients at the interim. The use of atherectomy during PCI has been previously shown to increase CK-MB release following PCI, triggering an endpoint in PROTECT II.
These results were observed “despite other significant treatment variables” that were identified in the interim report, including: two times the treatment of saphenous vein graft in the Impella arm, higher contrast media in the Impella arm, 32 percent of IAB but only 6 percent of Impella patients left the cath lab with device implanted and IAB patients had four times longer mean support (two hours of Impella support, nine hours of IAB support), Abiomed reported.
These data will be “utilized along with the presented USpella registry to help physicians identify the patients that receive maximum benefit from Impella as well as the small subset of patients where it may not be appropriate or for those that require longer support outside of the cath lab,” said O’Neill. “I look forward to the scientific presentation at the upcoming ACC in April.”