July 31, 2008 - Medtronic Inc. said today it initiated the first investigational sites in the U.S. to participate in PROTECT, the company’s global study comparing the Endeavor and Cypher drug-eluting stents on key safety metrics, including stent thrombosis.
Dr. Carlos Mego and his patient care team at Doctors Hospital at Renaissance in Edinburg, TX, enrolled the first U.S. patient in PROTECT last week.
“PROTECT is the first large-scale, prospective, randomized controlled trial focused primarily on the safety of drug-eluting stents, which remains an important concern among patients and physicians alike,” said Dr. William O’Neill, an interventional cardiologist and professor of medicine at the University of Miami School of Medicine in Florida. “The concern over stent safety centers primarily on the persistent issue of stent thrombosis, particularly after one year post-implant. This trial - the largest of its kind and the only with a global scope - is designed and powered to provide a thorough, long-term assessment of these stents’ safety among the diverse population of patients with coronary artery disease who constitute routine clinical practice.”
Initiated in May 2007 with the first implants in Europe, PROTECT will enroll a total of 8,800 patients, equally randomized to the Endeavor zotarolimus-eluting coronary stent from Medtronic or Johnson & Johnson’s Cypher sirolimus-eluting coronary stent, at more than 200 medical centers globally. Enrollment through July stands at nearly 5,500 patients, more than 60 percent of the total.
Collectively, data from PROTECT augments the comprehensive ENDEAVOR clinical program, which involves more than 21,000 patients; more than 15,000 of these patients will have received an Endeavor stent.
PROTECT sites in the U.S. will serve to provide the FDA with U.S.-specific data on the post-market experience with the Endeavor stent, which received FDA approval Feb. 1. The U.S. sites will enroll a minimum of 1,000 patients who receive Endeavor stents through PROTECT or, if necessary, through a nonrandomized continued-access arm.
“This trial, including at least 1,000 in the U.S. arm, will help further clarify the critical balance between safety and efficacy of drug-eluting stents in real-world practice,” said Dr. Laura Mauri, an interventional cardiologist at Brigham and Women’s Hospital and the chief scientific officer of the Harvard Clinical Research Institute in Boston.
Dr. Mauri has published widely on stent safety, and most recently was the senior author of an analysis that concluded that even a small absolute increase in DES thrombosis compared with BMS after one year would result in BMS being the preferred strategy for the overall percutaneous coronary intervention population and larger clinical trials with longer follow-up are needed to evaluate safety.
PROTECT is one such trial. With 8,800 patients, it is sufficiently powered to detect a clinically significant difference in rates of stent thrombosis between the Endeavor and Cypher stents. PROTECT’s primary endpoint is overall stent thrombosis at three years; secondary endpoints include death and non-fatal myocardial infarction (MI), as well as customary clinical efficacy endpoints, such as target lesion revascularization and target vessel revascularization. Enrollment is expected to be complete by December 2008, with three-year data on all study patients available in 2012.
Very late stent thrombosis (vLaST) - blood clotting inside the stent after one year post-implant - arose as a safety concern with the first generation of drug-eluting stents, including the Cypher stent and Boston Scientific’s Taxus paclitaxel-eluting coronary stent, in the fall of 2006, when the clinical trials that supported the regulatory approvals of these devices revealed a numerical increase in the rate of vLaST compared to their bare-metal stent controls. These first-generation drug-eluting stents have been associated with an annual rate of vLaST of approximately 0.3 percent through four years of follow-up.
The clinical trials that supported the regulatory approvals of the Endeavor stent have shown no increase in the rate of vLaST compared with its bare-metal stent control. Medtronic said the annual rate of vLaST with the Endeavor stent in the ENDEAVOR clinical program through four years of follow-up is 0.02 percent, with no events after two years. This observation served as the rationale for PROTECT.
For more information: www.medtronic.com