Normobaric Hyperoxia With Extended-Window Endovascular Therapy for Acute Ischemic Stroke (OPENS-EXTEND)

Inclusion Criteria: 1. Age 18 years or older. 2. Clinical signs and symptoms consistent with acute anterior-circulation ischemic stroke, with a National Institutes of Health Stroke Scale (NIHSS) score of 10 or greater at the time of randomization. 3. Pre-stroke modified Rankin Scale (mRS) score of 0 or 1. 4. Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 6 or greater on baseline non-contrast computed tomography or diffusion-weighted magnetic resonance imaging. 5. Eligible for endovascular therapy according to current guideline-recommended clinical practice and the judgment of the treating stroke team and neurointerventional team. 6. Randomization can be completed between 6 and 24 hours after the time the participant was last known well. Randomization and initiation of the study intervention must not cause an avoidable delay in endovascular therapy. 7. Pre-procedural computed tomography angiography or magnetic resonance angiography confirms large-vessel occlusion consistent with the participant's neurological deficits, involving one of the following: internal carotid artery or M1 segment of the middle cerebral artery. 8. Baseline level of consciousness score on item 1a of the NIHSS is 0 or 1. 9. Written informed consent has been obtained from the participant or the participant's legally authorized representative. Exclusion Criteria: * General Exclusion Criteria 1. NIHSS score of less than 10 at the time of randomization; substantial neurological improvement such that the participant is no longer considered eligible for endovascular therapy; or imaging-confirmed spontaneous recanalization with no remaining treatable target-vessel occlusion. 2. Seizure at stroke onset when the current neurological deficits are considered primarily attributable to a postictal state, or when a reliable baseline NIHSS assessment cannot be obtained. 3. Active clinically significant bleeding or a bleeding diathesis that, in the judgment of the investigator or treating clinical team, makes endovascular therapy or participation in the study unsafe. 4. Platelet count below 100 × 10⁹/L. 5. Clinically significant coagulation abnormality, anticoagulant exposure, or coagulation-factor deficiency that, according to the local standard of care at the participating center, makes the participant ineligible for endovascular therapy. 6. Severe or end-stage cardiac, hepatic, or renal dysfunction that is expected to substantially affect 90-day survival, functional outcome assessment, or the safety of study participation. 7. Persistent baseline blood glucose below 50 mg/dL (2.78 mmol/L) or above 400 mg/dL (22.20 mmol/L) after appropriate initial evaluation or correction. 8. Persistent systolic blood pressure above 185 mmHg or diastolic blood pressure above 110 mmHg despite appropriate antihypertensive treatment. 9. Life expectancy of less than 90 days because of a pre-existing disease or other underlying medical condition. 10. Known pregnancy. 11. Any of the following clinically significant respiratory diseases or conditions that, in the investigator's judgment, may make high-concentration oxygen therapy unsafe or interfere with reliable administration of the study intervention:chronic obstructive pulmonary disease; acute pulmonary infection; acute respiratory distress syndrome;clinically significant pleural effusion;chronic hypercapnic respiratory failure; another respiratory condition that may affect the safety of high-concentration oxygen therapy or the administration of the mask-based intervention. 12. Any of the following conditions before randomization: requirement for supplemental oxygen at a flow rate greater than 3 L/min to maintain peripheral oxygen saturation above 94%;requirement for noninvasive ventilatory support because of respiratory failure; or requirement for invasive mechanical ventilation because of respiratory failure. 13. Persistent clinically significant vital-sign instability after initial treatment, including but not limited to: heart rate of 50 beats per minute or lower or 120 beats per minute or higher; peripheral oxygen saturation of 90% or lower;respiratory rate of 10 breaths per minute or lower or 30 breaths per minute or higher; or other unstable vital signs considered by the investigator to potentially compromise participant safety. 14. Active vomiting, a high risk of aspiration, or inability to tolerate the study mask, except for participants who require clinically indicated endotracheal intubation and mechanical ventilation. 15. Active gastrointestinal bleeding. 16. History of a severe adverse reaction to iodinated contrast media that cannot be adequately managed with premedication, an alternative contrast strategy, or other appropriate clinical measures and therefore precludes endovascular therapy. 17. Current participation in another interventional clinical trial that may interfere with the study intervention, safety assessment, or evaluation of study outcomes. 18. Any other disease, condition, or circumstance that, in the investigator's judgment, makes the participant unsuitable for the study or may interfere with study treatment, participant safety, or outcome assessment. The specific reason must be documented. * Imaging Exclusion Criteria 1. Evidence of intracranial hemorrhage on baseline computed tomography or magnetic resonance imaging, including but not limited to intraparenchymal hemorrhage, subarachnoid hemorrhage, subdural hemorrhage, or epidural hemorrhage. 2. Failure to meet the prespecified perfusion-mismatch imaging criteria, including an ischemic core volume of 70 mL or greater. 3. Pre-randomization computed tomography angiography or magnetic resonance angiography demonstrates abnormal vascular anatomy or excessive vascular tortuosity such that, in the judgment of the treating neurointerventionalist, the target vessel cannot be safely accessed with endovascular devices or endovascular therapy is technically infeasible. 4. Based on the medical history, computed tomography angiography, magnetic resonance angiography, or other imaging findings, any of the following is suspected to be the primary cause of the index stroke and is considered to make endovascular therapy inappropriate or unsafe: cerebral vasculitis; aortic dissection; cervical arterial dissection; or intracranial arterial dissection. 5. Intracranial vascular occlusions involving multiple independent vascular territories, bilateral anterior-circulation infarction, or simultaneous anterior- and posterior-circulation infarction. A tandem lesion consisting of cervical internal carotid artery occlusion together with an intracranial large-vessel occlusion in the same vascular territory will not be automatically excluded if the treating neurointerventionalist considers endovascular therapy appropriate. 6. Confirmed moyamoya disease or moyamoya syndrome. 7. Substantial cerebral edema, mass effect, or midline shift on baseline computed tomography or magnetic resonance imaging. 8. Intracranial neoplasm that may affect the 90-day functional outcome, increase the risk of hemorrhage, or interfere with study assessment. A small, asymptomatic meningioma may be permitted at the investigator's discretion.