PROTECT IV RCT Underway

Gregg Stone, M.D., discusses the PROTECT IV randomized controlled trial (RCT). Dr. Stone is the international study primary investigator (PI) of PROTECT IV. PROTECT IV is a transcatheter heart failure therapy trial that is now underway. “I think it’s going to give us tremendous new insights into how to take care of some of these high-risk patients,” Dr. Stone states in his opening remarks. Dr. Stone is a professor of medicine at Mt. Sinai and a PI for more than 100 randomized controlled trials. He gave this presentation at the 2022 Technology and Heart Failure Therapeutics (THT) conference.

Dr. Stone introduces the PROTECT IV study by describing the complex and high-risk PCI (CHIP) patient population and asking the question, “By using mechanical circulatory support, can we improve their short-term or long-term outcomes?” This question underlies the PROTECT IV trial’s hypothesis: By providing hemodynamic stability during high-risk, complex PCI, Impella® will facilitate improved stent optimization and more complete revascularization that will translate into improved early and late outcomes.

Dr. Stone explains that PROTECT IV was designed to be a pivotal randomized trial to help fill a void of information about MCS in high-risk PCI. The trial, which is currently underway, will enroll between 1252 and 2500 patients with left ventricular dysfunction (LVD) meeting the criteria for heart failure with reduced ejection fraction (HFrEF) undergoing complex PCI at up to 120 centers. Patients will be randomized 1:1 to either Impella or the control group (intra-aortic balloon pump [IABP] or no MCS).

After reviewing the key inclusion and exclusion criteria, Dr. Stone describes key protocol provisions and study endpoints. The primary endpoint of PROTECT IV is a three-year composite of all-cause mortality, stroke, durable LVAD implant or heart transplant, MI or CV hospitalization measured when the last randomized patient reaches one-year follow-up. In addition, there are eight powered secondary endpoints that include hard clinical outcomes, quality of life outcomes and numerous other secondary pre-specified, non-powered endpoints.

Dr. Stone also describes the three major PROTECT IV substudies:

• Assessment of acute and chronic renal function
• Utility of right heart catheterization (RHC)
• Relationship between myocardial viability and global and regional LV function improvement and clinical outcomes according to revascularization