October 15, 2020
Shockwave IVL Meets Endpoints in the Pivotal DISRUPT CAD III Study
October 15, 2020—Shockwave Medical, Inc. announced that DISRUPT CAD III study of the Shockwave coronary intravascular lithotripsy (IVL) system met its primary safety and effectiveness endpoints. The company has submitted the data to the FDA to support the premarket approval application for the device.
DISRUPT CAD III is a prospective, multicenter, single-arm, global investigational device exemption (IDE) study of the Shockwave IVL system in de novo, calcified, stenotic, coronary arteries before to stenting.
The results were presented at TCT Connect, the 32nd annual Transcatheter Cardiovascular Therapeutics scientific symposium of the Cardiovascular Research Foundation held online October 14-18, 2020. The study was published simultaneously online by Jonathan M. Hill, MD, et al online in the Journal of the American College of Cardiology.
According to the company, the study enrolled 384 patients at 47 sites in the United States, France, Germany, and the United Kingdom, including 100 patients in an optical coherence tomography (OCT) substudy. All data were core-lab adjudicated.
The core lab determined that all lesions in the study were severely calcified. The average calcium lesion length was 47.9 mm and the average calcium arc was 292.5º, with a thickness of 0.96 mm at the site of maximum calcification as measured by OCT.
Shockwave reported that coronary IVL met both the safety and effectiveness goals in DISRUPT CAD III with a 30-day freedom from major adverse cardiovascular events (MACE) rate of 92.2% (P < .0001) and a procedural success rate of 92.4% (P < .0001), respectively. Additionally, coronary IVL before stent implantation was well tolerated with a low rate of major periprocedural clinical and angiographic complications.
The individual components of the 7.8% MACE rate included low rates of cardiac death (0.5 %), myocardial infarction (7.3%), and target vessel revascularization (1.6%) at 30 days after the index procedure.
Freedom from any serious angiographic complication after IVL delivery was 97.4% and at any point during the procedure was 96.9%. Coronary IVL showed a low risk of complications, including perforation (0.3%), major dissection (0.3%), abrupt closure (0.3%), and slow flow/no reflow (0%) at the end of the procedure.
Additionally, DISRUPT CAD III demonstrated the effectiveness of coronary IVL in treating calcium with large lumen gains that facilitated stent delivery. On the primary effectiveness endpoint of procedural success (92.4%), the individual endpoints included successful stent delivery in 99.2% of patients, a residual stenosis of < 50% in all cases, and no in-hospital MACE in 93% of patients.
Finally, Shockwave noted that despite the marked severity of the calcified lesions treated, IVL was able to cross and deliver therapy in 98.2% of lesions (377/384), which reflected successful stent delivery 99.2% of the time. At the end of the procedure post-stent, IVL resulted in an average acute gain of 1.7 mm and an average final in-stent residual stenosis of 11.9%.
Dean Kereiakes, MD, who served as coprincipal investigator of DISRUPT CAD III study, commented in Shockwave Medical's press release, “The correlation between calcium severity and poor percutaneous coronary intervention outcomes is well established and is a challenge we face on a daily basis in the cath lab. Given the severity of lesion and vessel calcium that was present in CAD III, it makes the findings of the study even more significant and noteworthy. The high rate of procedural success, combined with the low rate of major adverse cardiovascular events in CAD III, not only met the performance goals, but it also surpassed our expectations as investigators.”
In the United States, Shockwave's C2 coronary IVL catheters are limited to investigational use. The company stated that DISRUPT CAD III was based on a predicate study—the pivotal single-arm ORBIT II IDE study of Cardiovascular Systems, Inc.'s Diamondback 360 coronary orbital atherectomy system—to develop performance goals that would allow the FDA to evaluate the safety and effectiveness of IVL in a single-arm study. The devices are commercially available for the treatment of de novo coronary artery disease in Europe and select other geographies.