Landmark Neurology Trials

Here are just a few landmark neurology trials and articles every resident should know to keep up to date on important guidelines! More articles will be added periodically, so please check back!

For more, you may enjoy the mobile app "Stroke Trials," or this brief overview by the University of Pittsburgh residency program.


CHANCE Trial

TOPIC: Benefit of short term dual anti-platelets after mild non-AF stroke or TIA in secondary stroke prevention.

METHODS: Randomly assigned 5170 patients within 24 hours after the onset of minor ischemic stroke or high-risk TIA to combination therapy with clopidogrel and aspirin (clopidogrel at an initial dose of 300 mg, followed by 75 mg per day for 90 days) plus aspirin at a dose of 75 mg per day for the first 21 days) or to placebo plus aspirin (75 mg per day for 90 days).

CONCLUSION: “Among patients with TIA or minor stroke who can be treated within 24 hours after the onset of symptoms, the combination of clopidogrel and aspirin is superior to aspirin alone for reducing the risk of stroke in the first 90 days and does not increase the risk of hemorrhage.”


DAWN Trial

TOPIC: Thrombectomy 6-24 hours after onset of symptoms improves stroke outcome in selected patients.

METHODS: Enrolled patients with occlusion of the intracranial internal carotid artery or proximal middle cerebral artery who had last been known to be well 6 to 24 hours earlier and who had a mismatch between the severity of the clinical deficit and the infarct volume, with mismatch criteria defined according to age (<80 years or ≥80 years). Patients were randomly assigned to thrombectomy plus standard care (the thrombectomy group) or to standard care alone (the control group). Primary end points were mean score for disability on the utility-weighted modified Rankin scale and the rate of
functional independence at 90 days.

CONCLUSION: “Among patients with acute stroke who had last been known to be well 6 to 24 hours earlier and who had a mismatch between clinical deficit and infarct, outcomes for disability at 90 days were better with thrombectomy plus standard care than with standard care alone.”


SAMMPRIS Trial

TOPIC: Benefit of max medical management over stent for secondary stroke prevention in intracranial atherosclerosis.

METHODS: Randomly assigned patients who had a recent transient ischemic attack or stroke attributed to stenosis of 70 to 99% of the diameter of a major intracranial artery to aggressive medical management alone or aggressive medical management plus stenting. The primary end point was stroke or death within 30 days after enrollment or after a revascularization procedure for the qualifying lesion during the follow-up period or stroke in the territory of the qualifying artery beyond 30 days.

CONCLUSIONS: “In patients with intracranial arterial stenosis, aggressive medical management was superior to PTAS with the use of the Wingspan stent system, both because the risk of early stroke after PTAS was high and because the risk of stroke with aggressive medical therapy alone was lower than expected.”


NASCET Trial

TOPIC: Benefit of CEA over medical therapy for secondary stroke prevention after carotid stenosis-related stroke.

METHODS: Randomized trial of patients in two predetermined strata based on the severity of carotid stenosis (30 to 69 percent and 70 to 99 percent) who had had a hemispheric or retinal transient ischemic attack or a nondisabling stroke within the 120 days before entry and had stenosis of 70 to 99 percent in the symptomatic carotid artery. All patients received optimal medical care, including antiplatelet therapy. Those assigned to surgical treatment underwent carotid endarterectomy performed by neurosurgeons or vascular surgeons. All patients were examined by neurologists 1, 3, 6, 9, and 12 months after entry and then every 4 months.

CONCLUSIONS: “Carotid endarterectomy is highly beneficial to patients with recent hemispheric and retinal transient ischemic attacks or nondisabling strokes and ipsilateral high-grade stenosis (70 to 99 percent) of the internal carotid artery.”


CREST Trial

TOPIC: Difference in stenting versus CEA for standard risk patients with carotid stenosis.

METHODS: Randomly assigned patients with symptomatic or asymptomatic carotid stenosis to undergo carotid-artery stenting or carotid endarterectomy. The primary composite end point was stroke, myocardial infarction, or death from any cause during the periprocedural period or any ipsilateral stroke within 4 years after randomization.

CONCLUSIONS: “Among patients with symptomatic or asymptomatic carotid stenosis, the risk of the composite primary outcome of stroke, myocardial infarction, or death did not differ significantly in the group undergoing carotid-artery stenting and the group undergoing carotid endarterectomy. During the periprocedural period, there was a higher risk of stroke with stenting and a higher risk of myocardial infarction with endarterectomy.”