Medical Device Daily Associate
The first patient in the U.S. to be enrolled in Abbott Laboratories' (Abbott Park, Illinois) landmark clinical trial to assess the benefits of using stents in the neck arteries of likely stroke patients who have not shown symptoms of the disease was treated last week at the Hoag Heart and Vascular Institute at Hoag Memorial Hospital Presbyterian (Newport Beach, California).
The ACT I study, also known as the Carotid Angioplasty and Stenting vs. Endarterectomy in Asymptomatic Patients with Significant Extracranial Carotid Occlusive Disease Trial, is the first trial to study the potential benefits of minimally invasive carotid stenting in patients who normally would undergo a carotid endarterectomy (CEA) to prevent stroke. CEA is the current "gold standard" of treatment in asymptomatic patients, along with medication and lifestyle modification.
The company first disclosed its plans to initiate the trial in January (Medical Device Daily, Jan. 26, 2005)
Stroke represents the third-leading cause of death and the No. 1 cause of disability in the U.S. with more than 700,000 Americans suffering strokes each year. Nearly 90% of all strokes stem from insufficient blood supply to the brain, a condition caused by narrowing or blockage of embolic blood vessels.
ACT I is a multicenter, randomized study to compare carotid artery stenting to carotid artery surgery in asymptomatic patients – i.e., those who have not displayed symptoms of stroke, but who are at risk and who normally would be referred for surgery.
"This important clinical trial challenges the final frontier in carotid therapy by comparing carotid stenting with standard CEA in asymptomatic patients," said Subbarao Myla, MD, medical director of cardiovascular research at the Hoag Heart and Vascular Institute and the principal investigator for the ACT I study. "This has enormous importance since approximately 75% of carotid surgery in the country is done on such patients," he added.
The FDA recently approved carotid artery stenting for patients who require immediate intervention to prevent stroke, but it is limited to those who have medical conditions that deem them too high-risk for surgery (i.e., previous stroke or transient ischemic attack, congestive heart failure, unstable angina and severe lung disease).
Based on the FDA approval, the Centers for Medicaid & Medicare Services (CMS; Baltimore) said it would cover carotid artery stenting in those patients at high risk for carotid surgery. This development provided coverage for patients with a high level of carotid artery disease who are at risk of developing stroke.
In order to cover carotid artery stenting for a broader patient population, CMS needs solid data on which to base its decisions. This data doesn't currently exist for the asymptomatic stroke patient population, hence the ACT I trial.
Currently, CMS provides reimbursement for carotid stents in high-risk patients with stroke symptoms who are not good candidates for surgery, a potential patient population of roughly 15,000.
If Abbott's new trial shows carotid stents to be as effective as traditional surgery in preventing stroke in lower-risk patients, it could potentially expand coverage for the procedure to a much larger population. An estimated 175,000 CEAs were performed in the U.S. in 2003, with another 100,000 procedures done in other countries.
The trial, which is slated to enroll about 1,500 patients, was designed to establish the non-inferiority of CAS to CEA in this patient population. The company said that the trial will involve roughly 50 hospitals in the U.S., and will enroll at a roughly 3-to-1 ratio of CAS to CEA.
Its primary endpoints will be 30-day major adverse event (MAE) rates combining stroke, death and myocardial infarction and ipsilateral strokes between 31 and 365 days. Secondary endpoints include target lesion revascularization rate, device/procedural success rates, cumulative composite morbidity (nerve damage, wound complications, general anesthetic complications, etc.) and long-term ipsilateral stroke rates through five years of follow-up.
In addition to comparing clinical impacts, the study also will assess the relative economic and quality of life factors associated with CAS and CEA.
Abbott, via its Abbott Vascular Devices (Redwood City, California) division, is awaiting U.S. regulatory approval for a carotid stent for high-risk patients for whom surgery is not recommended and expects a decision in 2Q05. That approval is for the same system being used in the ACT I trial, the Xact carotid stent system coupled with the Emboshield embolic protection system
Physicians use these minimally invasive devices to treat carotid artery disease by placing a stent in the carotid artery to restore unrestrained blood flow to the brain. The stent is brought into position in the carotid artery via thin catheters that are threaded through the vascular system from a small access site – typically made in the femoral artery in the groin. A special device called an embolic protection filter is opened up like an umbrella downstream from the stenting procedure to protect the patient's brain by catching emboli (plaque) that may be dislodged during the procedure.
Abbott, which has an exclusive agreement with MedNova (Galway, Ireland) to distribute the EmboShield filter and Xact carotid stent products, is one of many companies competing in this very promising space in both the U.S. and abroad.
Other firms developing distal protection devices and carotid stents include Cordis Endovascular (Warren, New Jersey), whose carotid artery stent system is comprised of the Nitinol Self-Expanding Stent and the Angioguard Emboli Capture Guidewire; Boston Scientific (Natick, Massachusetts), with the FilterWire EZ and Carotid Wallstent; EndoTex Interventional Systems (Cupertino, California) with the NexStent, now under evaluation in the CABERNET trial; Medtronic (Minneapolis) with the PercuSurge balloon occlusion system; the Vascular Systems unit of B. Braun Medical (Melsungen, Germany); and Rubicon Medical (Salt Lake City), with the Rubicon Filter.
In the U.S., the Emboshield and the Xact system are investigational devices not yet approved for sale, though both devices already have the CE mark.