First Patient Enrolled in PROTECT IV Randomized Controlled Trial of Impella® Heart Pumps

The first patient has been enrolled in PROTECT IV, a large, prospective, multi-center randomized controlled trial (RCT) that is designed to provide the level of clinical evidence needed to achieve a Class I guideline/recommendation for Impella support for high-risk percutaneous coronary intervention (HRPCI). The first patient was enrolled at Ascension St. John Hospital in Detroit by Dr. Ted Schreiber, chief of cardiology at Ascension St. John Macomb-Oakland Hospital and Dr. Amir Kaki, interventional cardiologist and director of mechanical circulatory support at Ascension St. John Hospital.

The two-arm trial will compare the benefits of HRPCI with Impella versus HRPCI without Impella support. The primary endpoint of the study is the composite of all-cause death, stroke, myocardial infarction (MI) or hospitalization for cardiovascular (CV) causes at a minimum of one year. The trial has an adaptive design. It aims to enroll 1,252 consecutive qualified patients at more than 100 hospital sites across the U.S. and Europe.

The PROTECT IV RCT will leverage advancements in technology and best practices learned since the completion of the PROTECT II RCT and the FDA pre-market approval (PMA) for Impella 2.5® for HRPCI. Data from PROTECT II found, when compared to intra-aortic balloon pump (IABP), Impella 2.5 led to a 29% reduction in MACCE, defined as composite of death, stroke, myocardial infarction and repeat procedures, at 90 days.

PROTECT IV also builds on PROTECT III, a contemporary, prospective, single-arm FDA post-approval study of Impella 2.5 and Impella CP® for HRPCI. PROTECT III results presented at TCT 2020 found a statistically significant improvement in 90 day MACCE rates versus PROTECT II (15.0% vs. 21.9%, p=.035) with lower in-hospital bleeding complications (1.8% vs. 12.5%, p<0.001) despite substantially sicker and more complex patients. Impella-supported PCI has shown higher rates of optimal and complete revascularization, which leads to improved long-term survival and quality-of-life.

“This trial aims to generate the highest level of scientific clinical evidence to definitively demonstrate that Impella-supported PCI improves outcomes for high-risk patients, and we are excited to enroll the first patient in the trial,” said Dr. Schreiber. “Dr. Kaki and I are proud of the entire team at Ascension St. John Hospital for being at the forefront of cardiovascular research in this landmark RCT.”

The trial’s principal investigators are: Gregg W. Stone, MD, professor of medicine, professor of population health sciences and policy and director of academic affairs for the Mount Sinai Heart Health System and co-director of medical research and education at The Cardiovascular Research Foundation; and Stephan Windecker, MD, director and chief physician in the department of cardiology at the Swiss Cardiovascular Center in Bern, Switzerland.

“PROTECT IV is a landmark trial with the potential to revolutionize the interventional treatment of patients with complex coronary artery disease and left ventricular dysfunction,” said Dr. Stone. “This academically-led study is designed to provide the highest level of robust evidence to guide management and improve global clinical outcomes for these high-risk patients.”

“This study is important for the field of interventional cardiology in that it will demonstrate whether forward flow unloading will protect the heart during a high-risk PCI, allowing for more complete revascularization and improved long-term outcomes,” said Dr. Windecker.