Last month the DISRUPT CAD III investigators, led by co-PIs Drs. Dean Kereiakes and Jonathan Hill, published in the American Heart Journal the trial design and rationale paper titled, “Evaluation of safety and efficacy of coronary intravascular lithotripsy for treatment of severely calcified coronary stenoses: Design and rationale for the Disrupt CAD III trial.”
As the trial results are eagerly awaited, we recently had a chance to connect with Dr. Kereiakes, M.D., FACC, FSCAI, Medical Director of The Christ Hospital Heart and Vascular Center and the Christ Hospital Research Institute, Professor of Clinical Medicine, The Ohio State University, to get his key takeaways on what makes this study unique, which endpoints matter most to his peers from the study and where it ranks among his vast accomplishments in leading pivotal studies of first-in-class technologies. We hope you enjoy his perspective.
- What makes this study unique compared to your typical IDE stent study?
In Disrupt CAD III we set out to enroll the most severely calcified arteries ever enrolled into a clinical trial by using study inclusion criteria of greater than 15-millimeters of calcification angiographically on both sides of the vessel or a calcium arc by intravascular imaging of greater than 270 degrees. By doing that, we hoped to have a population with the longest calcified length of artery, the greatest arc of calcium, and the greatest thickness of calcium included into any study of a calcium modification technology to date.
- What benefits come from using a predicate study for the CAD III design?
The benefits of using a predicate study allowed us to design a single arm study, non-randomized. This approach facilitated rapid enrollment and rapid operator proficiency with the technology under the “practice makes perfect” concept. We also benefited by using established endpoints from the ORBIT II study which were turned into performance goals, in collaboration with FDA, so that we could establish measurement targets for IVL safety and effectiveness outcomes in DISRUPT CAD III.
- What was the most challenging part of running this study?
The most challenging part of running this study was finding severely calcified arteries that qualified to participate in the study based on the “high bar” set by the inclusion criteria. We had a lot of screen failures. It was also difficult to find patients that were biomarker negative, meaning that you could not have positive biomarkers and be entered into the trial because those patients were excluded from Orbit II, the predicate study. Many target lesions that we would have considered heavily calcified did not meet the rigid inclusion criteria of having 15-millimeter length of calcium on both sides of the vessel or an arc of calcium exceeding 270 degrees. Finally, the COVID19 pandemic was disruptive to the completion, follow-up and analysis of trial data.
- Out of all of the endpoints being captured in the study, in which are your peers are most interested?
Thinking about this group of patients and the outcomes that are normally achieved, my peers are most interested in the endpoints of MACE and stent expansion on OCT. MACE was defined as the composite occurrence of cardiac death, myocardial infarction , or target vessel revascularization at 30 days, which are important safety parameters. As far as an efficacy parameter for the technology, in my mind stent expansion is probably the most important. Why? We know that stent under-expansion is one of the most powerful drivers of both thrombosis and restenosis, and stent under-expansion is proportional to the degree of vessel calcification in prior studies. Therefore, we would have legitimate concerns that many patients could have stent under-expansion if the technology were not effective.
- Of the many studies that you’ve lead as principal investigator in your impressive career, where does CAD III rank?
Most recently I have been principal investigator for Evolve II which evaluated the first-in-class bioabsorbable polymer stent, and ABSORB III, which evaluated the first-in-class bioabsorbable scaffold. I am similarly excited by this first-in-class calcium modification technology. It is a unique device that addresses an increasing challenge that we face in both coronary and peripheral interventions. The increasing age, increasing prevalence of diabetes, and increasing prevalence of chronic kidney disease in patients undergoing vascular intervention, all contribute to an increasing prevalence of severe calcification in the coronary and peripheral vessels, which makes intravascular lithotripsy very relevant now and in the years to come.
Important Safety Information - Coronary IVL
Caution: In the United States, Shockwave C2 Coronary IVL catheters are investigational devices, limited by United States law to investigational use in the DISRUPT CAD III Study. Shockwave C2 Coronary IVL catheters are commercially available in certain countries outside the U.S. Please contact your local Shockwave representative for specific country availability. The Shockwave C2 Coronary IVL catheters are indicated for lithotripsy-enhanced, low-pressure balloon dilatation of calcified, stenotic de novo coronary arteries prior to stenting. For the full IFU containing important safety information please visit: https://swmedstage.wpengine.com/clinicians/international/coronary/shockwave-c2/
