Now that Xience V is approved in the U.S., Abbott (Abbott Park, Illinois) is not wasting any time finding out how the second-generation drug-eluting stent performs in the real world. The company said six hospital centers are already enrolling patients in the XIENCE V USA post-approval study just one week after FDA approved the device.

The XIENCE V USA study will evaluate the safety and effectiveness of the Xience V everolimus-eluting coronary stent in a real-world clinical setting out to five years, Abbott said. Jack Jones, MD, an interventional cardiologist and medical director of the Stormont-Vail Catheterization Lab (Topeka, Kansas), was one of the first doctors to enroll a patient into the study.

"Xience V is an important innovation that gives patients in the U.S. access to a next-generation drug eluting stent that has been shown in clinical trials to improve patient outcomes," Jones said. "During the stent procedure, we found it easy to deliver Xience V to the diseased portion of the vessel. With its combination of clinical efficacy and deliverability, I believe that Xience V will become a key advancement in the treatment of coronary artery disease."

Unlike the SPIRIT trials evaluating Xience V in a very controlled patient population, James Hermiller, MD, an interventional cardiologist at St. Vincent Heart Center of Indiana (Indianapolis) and the principal investigator of the XIENCE V USA study, told Medical Device Daily that the post-approval study will be open to any patient who receives the device, so long as they give their consent to be in the trial.

Because there will be no patient exclusions, XIENCE V USA will provide a better idea of how the stent performs in a real-world setting than the company's SPIRIT trials, Hermiller said.

Jonathon Hamilton, an Abbott spokesman, told MDD that the trial would enroll at least 5,000 coronary artery disease patients in about 250 hospital centers across the U.S. The primary endpoint of the study is a measure of stent thrombosis (formation of blood clots) every year out to five years, as defined by the Dublin/Academic Research Consortium (ARC). The ARC definition of late stent thrombosis was developed to eliminate variability in the definitions across various drug eluting stent trials.

The co-primary endpoint of the study is the composite rate of cardiac death and any heart attack (Q-wave or non-Q-wave myocardial infarction) in patients at one year, Abbott said. Secondary endpoints of the study include patient compliance with prescribed anti-platelet medication, measures of re-treatment by stenting or surgery, and device and procedural success.

"Post-approval studies allow physicians to follow the safety and efficacy of new treatments in a more complex patient population than is typically studied in pre-approval clinical trials. XIENCE V USA will provide significant insight about the performance of Abbott's new drug-eluting stent in a variety of patients," said Charles Simonton, MD, divisional VP of medical affairs and chief medical officer at Abbott Vascular (Santa Clara, California), the company's vascular care business. "Our ability to work with our physician partners to begin this post-approval study within days of FDA approval is further evidence of Abbott's commitment to help the interventional cardiology community gain additional insights about the clinical benefits of XIENCE V."

Xience received FDA approval last week (Medical Device Daily, July 7, 2008). The stent is used to treat heart disease by propping open a narrowed or blocked artery and releasing the drug, everolimus, in a controlled manner to prevent the artery from becoming blocked again following a stent procedure, Abbott said.

The stent will be available on both over-the-wire and rapid exchange delivery systems. The device is based on Abbott's Multi-Link Vision bare-metal stent platform, which is designed to facilitate ease of delivery, the company said.

Medtronic's (Minnepolis) Endeavor zotarolimus-eluting stent, which won approval in February, was the first second-generation DES to hit the U.S. market (MDD, Feb. 4, 2008). Both the Endeavor and Xience are expected to elbow aside the first-generation DES devices, the Cypher from Johnson & Johnson's (New Brunswick, New Jersey) Cordis (Miami Lakes, Florida) unit, and the Taxus from Boston Scientific (Natick, Massachusetts).

Abbott also supplies a private-label version of Xience V to Boston Scientific called the Promus.

Xience was launched in Europe and other international markets in October 2006. It is an investigational device in Japan and is currently under review for approval by Japan's Ministry of Health, Labor and Welfare and the Pharmaceuticals and Medical Devices Agency.

Everolimus, developed by Novartis Pharma (Basel, Switzerland), is a proliferation signal inhibitor, or mTOR inhibitor, licensed to Abbott for use on its drug-eluting stents. The drug has been shown to inhibit in-stent neointimal growth in the coronary vessels following stent implantation, due to its antiproliferative properties, the company noted.

Xience is backed by long-term clinical data from a total of 1,362 patients enrolled in the SPIRIT FIRST, SPIRIT II and SPIRIT III trials. FDA approval of the stent was based, in large part, on results from the 1,002 patient SPIRIT III U.S. pivotal clinical trial, in which the device demonstrated a 45% reduction in the risk of major adverse cardiac events compared to Taxus at two years. Abbott said

Xience also demonstrated a 32% reduction in target vessel failure compared to Taxus at two years, and a low rate of stent thrombosis between one and two years. Xience met its primary endpoint in the SPIRIT III trial with a statistically significant 50% reduction in vessel renarrowing at eight months compared to Taxus, the company noted.