Introduction: The role of endovascular thrombectomy (EVT) for acute extra-large ischemic stroke patients with large vessel occlusion (LVO) is uncertain. We aimed to explore the clinical and safety outcomes of medical management (MM) plus EVT (EVT group) versus MM alone (MM group) among acute extra-large ischemic stroke patients with LVO within 24 h of last known well. Methods: XL STROKE (EVT for extra-large ischemic stroke) is an investigator-initiated, nationwide, prospective registry with blinded end point assessment performed at approximately 60 sites in China and will enroll up to 990 acute ischemic stroke patients within 24 h of last known well. Imaging inclusion criteria are occlusion of the internal carotid artery or the middle cerebral artery M1 or M2 segments, and Alberta Stroke Program Early Computed Tomography Score of 0 to 2 or an ischemic core volume ≥85 mL. All patients will be dichotomized into EVT group and MM group according to whether they received EVT or not. The primary outcome is the level of disability on the modified Rankin Scale at 90 ± 14 days. Safety outcomes include symptomatic intracranial hemorrhage within 48 h and mortality at 90 ± 14 days. Conclusion: Results from XL STROKE registry will provide constructive evidence of improved disability outcomes and safety with EVT for acute extra-large ischemic stroke patients with LVO within 24 h of last known well.

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