Although endovascular therapy (EVT) has substantially improved recanalization rates and extended the treatment window for acute ischemic stroke, fewer than half of patients achieve functional independence despite successful reperfusion. Growth of the ischemic core before reperfusion and ischemia-reperfusion injury after recanalization may contribute to unfavorable outcomes. Therefore, an adjunctive neuroprotective strategy that preserves the ischemic penumbra before and during EVT may further improve clinical outcomes.
Normobaric hyperoxia (NBO) is a noninvasive and readily available treatment that delivers high-concentration oxygen at normal atmospheric pressure. By increasing oxygen delivery to hypoperfused but potentially salvageable brain tissue, NBO may delay infarct growth, preserve the blood-brain barrier, and reduce reperfusion injury. Previous preclinical studies and early clinical trials have suggested that NBO may provide neuroprotection without increasing oxidative stress or other major safety risks. The previous OPENS-1 and OPENS-2 trials showed that periprocedural NBO combined with EVT reduced infarct volume and improved 90-day functional outcomes in patients treated within 6 hours after stroke onset. In addition, a preliminary two-center study involving 120 patients treated 6-24 hours after onset suggested greater early neurological improvement and a potentially favorable 90-day functional outcome with NBO plus EVT compared with EVT alone.
OPENS-EXTEND is a prospective, multicenter, randomized controlled trial designed to evaluate the efficacy and safety of periprocedural NBO as an adjunct to EVT in patients with acute ischemic stroke caused by anterior-circulation large-vessel occlusion who present 6-24 hours after symptom onset or last known well and have imaging evidence of salvageable ischemic brain tissue. Participants will be randomly assigned to receive either EVT combined with NBO or EVT with standard medical management alone. The primary hypothesis is that adjunctive NBO will improve functional outcomes at 90 days without increasing safety risks.
Inclusion Criteria:
Exclusion Criteria:
General Exclusion Criteria
Imaging Exclusion Criteria
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.
Failure to meet the prespecified perfusion-mismatch imaging criteria, including an ischemic core volume of 70 mL or greater.
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.
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.
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.
Confirmed moyamoya disease or moyamoya syndrome.
Substantial cerebral edema, mass effect, or midline shift on baseline computed tomography or magnetic resonance imaging.
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.
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Participants assigned to this arm will receive normobaric hyperoxia in addition to endovascular therapy and guideline-recommended standard medical care. Normobaric hyperoxia will be initiated as soon as possible and within 30 minutes after randomization. Participants who are not intubated will receive oxygen through a non-rebreather mask at a flow rate of 10 L/min for 4 hours. For participants requiring endotracheal intubation, oxygen will be delivered through a mechanical ventilator with the fraction of inspired oxygen set at 1.0 during the 4-hour intervention period.
Participants assigned to this arm will receive sham normobaric hyperoxia in addition to endovascular therapy and guideline-recommended standard medical care. The sham intervention will be initiated as soon as possible and within 30 minutes after randomization. Participants who are not intubated will wear the same type of non-rebreather mask used in the experimental arm, with the oxygen flow set at 1 L/min and the mask valves modified to allow entrainment of ambient air. The sham intervention will continue for 4 hours. For participants requiring endotracheal intubation, ventilation will be provided with the fraction of inspired oxygen set at 0.3 during the 4-hour intervention period.
Normobaric Hyperoxia Combined With Endovascular Treatment in Acute Ischemic Stroke (OPENS-2)
Normobaric Hyperoxia Combined With Endovascular Treatment for Acute Ischemic Stroke
Normobaric Hyperoxia Combined With Intravenous Thrombolysis for Acute Ischemic Strokeļ¼Longterm Outcome (OPENS-3L)
Normobaric Hyperoxia Combined With Intravenous Thrombolysis for Acute Ischemic Stroke (OPENS-3)
Normobaric Hyperoxia Combined With Endovascular Therapy in Patients With Stroke Within 6 Hours of Onsetļ¼Longterm Outcome
Normobaric Hyperoxia Combined With Reperfusion for Acute Ischemic Stroke
Treatment Duration on Normobaric Hyperoxia in Acute Ischemic Stroke
Oxygen Concentration Target in Stroke Endovascular Treatment