Original Article
Design of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis Trial

https://doi.org/10.1016/j.jstrokecerebrovasdis.2011.05.001Get rights and content

Background

Patients with recent transient ischemic attack (TIA) or stroke caused by 70% to 99% stenosis of a major intracranial artery are at high risk of recurrent stroke on usual medical management, suggesting the need for alternative therapies for this disease.

Methods

The Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis trial is an ongoing, randomized, multicenter, 2-arm trial that will determine whether intracranial angioplasty and stenting adds benefit to aggressive medical management alone for preventing the primary endpoint (any stroke or death within 30 days after enrollment or after any revascularization procedure of the qualifying lesion during follow-up, or stroke in the territory of the symptomatic intracranial artery beyond 30 days) during a mean follow-up of 2 years in patients with recent TIA or stroke caused by 70% to 99% stenosis of a major intracranial artery. Aggressive medical management in both arms consists of aspirin 325 mg per day, clopidogrel 75 mg per day for 90 days after enrollment, intensive risk factor management primarily targeting systolic blood pressure <140 mm Hg (<130 mm Hg in diabetics) and low density cholesterol <70 mg/dL, and a lifetsyle modification program. The sample size required to detect a 35% reduction in the rate of the primary endpoint from angioplasty and stenting based on the log-rank test with an alpha of 0.05, 80% power, and adjusting for a 2% loss to follow-up and 5% crossover from the medical to the stenting arm is 382 patients per group.

Results

Enrollment began in November 2008 and 451 patients have been enrolled as of March 31, 2011.

Conclusions

This is the first randomized stroke prevention trial to compare angioplasty and stenting with medical therapy in patients with intracranial arterial stenosis and to incorporate intensive management of multiple risk factors and a lifestyle modification program in the study design. Hopefully, the results of the trial will lead to more effective therapy for this high-risk disease.

Section snippets

Overall Design

SAMMPRIS is an ongoing, investigator-initiated, randomized clinical trial funded by the National Institute of Neurological Disorders and Stroke (NINDS) that is being conducted at 50 sites in the United States. The primary aim is to determine whether PTAS (using the Gateway PTA balloon catheter and Wingspan Stent System; both manufactured by Boston Scientific Corporation, Natick, MA) combined with aggressive medical management is superior to aggressive medical management alone for preventing the

Statistical Considerations

The expected mean duration of follow-up is 2 years (range 1-3 years). The sample size required to have 80% power to detect a 35% relative risk reduction in the primary endpoint (estimated rate 24.7% at 2 years in the medical arm v 16.1% in the PTAS arm) using a 2-sided log-rank test with probability of a Type I error = 0.05, a 2% lost to follow-up rate, and a 5% crossover from the medical to the PTAS arm is 382 patients per group. The primary endpoint rate for the medical therapy alone group

Data and Safety Monitoring Board

The DSMB meets every 6 months to review the study progress and accumulated data. The main responsibilities of the DSMB are to ensure that study participants are not exposed to unnecessary or unreasonable risks and that the trial is conducted with high scientific and ethical standards. The DSMB is assisted by 2 safety monitors (1 medical, 1 interventional) who review data on individual cases with adverse events. Two interim efficacy analyses are planned for when approximately 33% and 66% of the

Monitoring the Performance of PTAS in the Trial

To ensure patient safety and adherence to the PTAS protocol, the procedure notes from all PTAS procedures are reviewed. PTAS procedure data is first reviewed by the clinical research nurse at the statistical center. If an adverse event is identified, data related to the event (including the interventional procedure note) are promptly referred to the interventional safety monitor for review. Any concerns regarding procedural technique or protocol compliance are relayed to the DSMB and the

Why were patients with remote symptoms and 50% to 69% stenosis excluded from SAMMPRIS?

WASID showed that severity of stenosis was the most powerful predictor for recurrent stroke in the territory of the stenotic artery. The cumulative rates of stroke in the territory in patients with ≥70% stenosis were 18% at 1 year and 19% at 2 years, whereas the rates of stroke in the territory in patients with <70% stenosis were 6% at 1 year and 10% at 2 years.7 Time from qualifying event to enrollment was also a powerful predictor of recurrent stroke, especially in patients with 70% to 99%

Unique Features of SAMMPRIS Design

SAMMPRIS has several unique design features that may be worth incorporating into future secondary prevention trials in stroke. First, we are using aggressive protocol driven management of multiple vascular risk factors as part of the study protocol, with regular performance feedback and suggestions from the coordinating center to improve risk factor management at each site. Second, a lifestyle modification program is used to coach patients about healthy habits. Third, in deciding the

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    Funded by a research grant (U01 NS058728) from the US Public Health Service National Institute of Neurological Disorders and Stroke (NINDS). Other support is provided in the acknowledgment section.

    1

    See appendix for list of study investigators.

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