SAMMPRIS Trial: ICAD Stenting vs Medical
In patients with symptomatic 70–99% intracranial atherosclerotic stenosis within 30 days of qualifying TIA or stroke, does percutaneous transluminal angioplasty + Wingspan stenting plus aggressive medical management reduce 30-day stroke/death compared with aggressive medical management alone? (Stopped early by DSMB for harm + futility.)
Chimowitz et al. (NEJM 2011;365(11):993–1003) · doi:10.1056/NEJMoa1105335 · 451 patients
Population
Included
- Recent (≤30 days) TIA or non-disabling ischemic stroke
- 70–99% angiographically verified stenosis of a major intracranial artery
- Aggressive medical management eligibility
- Symptomatic ICAS in the target territory
Eligible patients
- Transient ischemic attack or nondisabling ischemic stroke within 30 days before enrollment
- Stroke or TIA attributed to angiographically verified stenosis of 70 to 99% of the diameter of a major intracranial artery
- Written informed consent; patients not undergoing diagnostic angiography as part of routine care consented to angiography per the study protocol
Excluded
- Asymptomatic intracranial stenosis
- Disabling stroke (mRS >3)
- Recent surgery or hemorrhagic disorder
- Hemodynamic-failure selection (separate evidence base)
- Post-AMM failure (salvage stenting; addressed by WEAVE on-label registry)
Symptom timing and stenosis severity
- Symptoms that occurred more than 30 days before enrollment
- Stenosis of 50 to 69% of an intracranial artery (lower stroke risk on standard medical therapy, making benefit from PTAS unlikely)
Other (per published study protocol)
- Other eligibility criteria are described in the study protocol available with the full text at NEJM.org
Source: Chimowitz MI et al., N Engl J Med 2011· Retrieved 2026-06-09
Primary Outcome
STOPPED FOR HARM: DSMB halted SAMMPRIS at 451 of 764 planned patients due to excess 30-day stroke/death in the stenting arm (14.7% vs 5.8%, P=0.002). Periprocedural events drove the harm — 25 of 33 PTAS strokes occurred within 24 hours of the procedure. sICH 4.5% vs 0%. Result is specific to Wingspan as INITIAL therapy in this population; on-label salvage use (WEAVE registry) showed acceptable safety.
Stroke/death within 30 Days
Study Arms
- Agent
- Percutaneous transluminal angioplasty and stenting (Gateway PTA balloon and Wingspan self-expanding stent, Boston Scientific) plus aggressive medical management
- Dose
- Self-expanding Wingspan stent after Gateway balloon angioplasty; clopidogrel 600 mg loading dose 6 to 24 hours before PTAS for patients not already taking clopidogrel 75 mg daily for at least 5 days
- Route
- Endovascular (intracranial), under general anesthesia
- Frequency
- Single procedure within 3 business days after randomization
- Duration
- One-time procedure; aggressive medical management continued as in the control arm
- Co-interventions
- Identical aggressive medical management in both groups: aspirin 325 mg daily plus clopidogrel 75 mg daily for 90 days after enrollment, target systolic blood pressure below 140 mmHg (below 130 mmHg if diabetic), target LDL cholesterol below 70 mg/dL with rosuvastatin, plus a lifestyle modification program
PTAS in this initial-treatment role caused excess 30-day stroke or death (14.7% vs 5.8%); the trial was stopped early by the data and safety monitoring board for harm plus futility
- Agent
- Aggressive medical management
- Dose
- Aspirin 325 mg daily plus clopidogrel 75 mg daily for 90 days after enrollment
- Route
- Oral plus risk-factor and lifestyle management
- Frequency
- Daily antiplatelet therapy
- Duration
- Dual antiplatelet for 90 days; risk-factor management ongoing
- Co-interventions
- Target systolic blood pressure below 140 mmHg (below 130 mmHg if diabetic), target LDL cholesterol below 70 mg/dL with rosuvastatin, plus a lifestyle modification program
Control arm outperformed historical WASID medical controls; first-line strategy for symptomatic intracranial atherosclerotic stenosis
Safety
Symptomatic ICH ≤30 days (DOMINANT HARM)
4.5%
0%
10/224 PTAS vs 0/227 AMM (P=0.04, Fisher exact). Of 33 strokes in PTAS within 30 days, 25 (76%) occurred within 1 day of the procedure.
Death (full follow-up)
3.1%
3.1%
7/224 PTAS vs 7/227 AMM. Death rates similar overall; the harm signal is in stroke morbidity, not mortality.
Trial Design
Type
- Randomized open-label trial
- Stopped early due to harm
- 1:1 allocation (Stenting vs. Medical)
Timeline
Enrolled 2008-2011 (stopped early)
N
451
Enrollment
451 patients at 50 US sites. Enrolled Nov 2008 – Apr 2011 (halted by DSMB). Gateway PTA balloon + Wingspan self-expanding stent (Stryker Neurovascular). Published NEJM 2011. Erratum 2012 (procedural bookkeeping only; no statistical change).
ClinicalTrials.gov
NCT00576693Bedside Pearl
Wingspan stenting as INITIAL therapy for symptomatic ICAS 70–99% within 30 days of TIA/stroke is harmful (14.7% vs 5.8% 30-day stroke/death). AHA/ASA 2021 Class III. Aggressive medical management (DAPT 90d + high-intensity statin + SBP <140) is first-line. Reserve stenting for documented AMM failure (see WEAVE on-label registry context).