NINDS Halts SAMMPRIS Trial of Intracranial Angioplasty With Stenting

April 11, 2011—The National Institute of Neurological Disorders and Stroke (NINDS) has issued a clinical alert that it has stopped enrollment in the SAMMPRIS (Stenting vs Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis) trial. SAMMPRIS is aimed at evaluating whether intracranial angioplasty combined with stenting adds benefit to aggressive medical therapy for preventing stroke in patients with symptomatic intracranial arterial stenosis. The study's principal investigator is Marc I. Chimowitz, MD, of the Medical University of South Carolina. More information is available on the SAMMPRIS Web site.

Acting on the recommendation of the study's data safety monitoring board and in concurrence with the SAMMPRIS executive committee, NINDS decided that enrollment in the study should be stopped and that the trial data currently available indicate that aggressive medical management alone is superior to angioplasty combined with stenting in patients with recent symptoms and high-grade intracranial arterial stenosis.

According to NINDS, SAMMPRIS is the first prospective, randomized, multicenter trial to compare aggressive medical management alone versus aggressive medical management plus angioplasty combined with stenting in patients with symptomatic high-grade (70%–99%) stenosis of a major intracranial artery (intracranial carotid, middle cerebral artery, intracranial vertebral artery, and basilar artery).

In the study, all patients were enrolled within 30 days after a transient ischemic attack or nondisabling stroke that was attributed to intracranial arterial stenosis. Aggressive medical management in both arms consisted of aspirin 325 mg/day for the entire follow-up, clopidogrel 75 mg/day for 90 days after enrollment, intensive management of vascular risk factors (primarily targeting systolic blood pressure < 140 mm Hg [if diabetic, < 130 mm Hg] and low-density lipoprotein < 70 mg/dL), and provision of a lifestyle modification program to all study patients.

Recruitment in SAMMPRIS began in November 2008 and was halted on April 5, 2011 after 451 (59%) of the planned 764 patients had been enrolled at 50 participating sites in the United States.

At the time of the most recent data safety monitoring board review, 14% of patients treated with angioplasty combined with stenting experienced a stroke or died within the first 30 days after enrollment compared with 5.8% of patients treated with medical therapy alone, a highly significant difference.

The 30-day rate of stroke or death for patients in the intensive medical treatment alone arm is substantially lower than the estimated rate of 10.7% based on historical controls, most of whom received standard medical care. In addition, the 30-day rate of stroke or death in the stented patients is substantially higher than the estimated rate of 5.2% to 9.6% based on registry data.

There were five stroke-related deaths within 30 days after enrollment, all in the stenting arm. There was one nonstroke-related death in the medical arm within 30 days after enrollment. Beyond 30 days, the rates of stroke in the territory of the stenotic artery are similar in the two groups, but fewer than half of the patients have been followed for 1 year. As such, follow-up of currently enrolled patients and comprehensive analysis of the total trial data set will be important in the final interpretation of this study, NINDS advised.

The angioplasty and stenting system used in the trial is the Wingspan stent system with the Gateway percutaneous transluminal angioplasty balloon catheter (Boston Scientific Corporation, Natick, MA). The Gateway-Wingspan system received US Food and Drug Administration approval in June 2009 for use in improving cerebral artery lumen diameter in patients with intracranial atherosclerotic disease, refractory to medical therapy, in intracranial vessels with ≥ 50% stenosis that are accessible to the system. Boston Scientific provided the device and support for third party monitoring but no other financial support of SAMMPRIS, Dr. Chimowitz advised.