Adjunctive Normobaric Hyperoxia With Endovascular Thrombectomy for Acute Stroke at 6 to 24 Hours: A Phase IIb Randomized Trial

BACKGROUND: Normobaric hyperoxia (NBO) is a simple neuroprotective strategy that may augment endovascular thrombectomy (EVT) in acute ischemic stroke. We evaluated the safety and preliminary efficacy of NBO plus EVT in patients with large-vessel occlusion presenting 6 to 24 hours after onset. METHODS: In this phase IIb, randomized, assessor-blinded, controlled trial conducted at 2 academic comprehensive stroke centers in China, patients aged ≥18 years with anterior circulation large-vessel occlusion presenting 6 to 24 hours after acute ischemic stroke onset were assigned 1:1 to EVT+NBO or EVT alone. The NBO group received 100% oxygen via a face mask at 10 L/min for 4 hours, starting before recanalization. The primary end point was early neurological improvement (≥30% reduction in the National Institutes of Health Stroke Scale score at 24 hours). Primary analyses used adjusted regression models controlling for prespecified prognostic covariates. Secondary end points included infarct volume at 24 to 48 hours and the modified Rankin Scale score at 90 days. Safety outcomes were mortality, intracranial hemorrhage, and symptomatic intracranial hemorrhage. Analyses followed the intention-to-treat principle. Early neurological improvement was analyzed using an adjusted binomial regression model, and the 90-day modified Rankin Scale shift was analyzed using an adjusted ordinal logistic regression model, controlling for age, sex, intravenous thrombolysis, and occlusion site. RESULTS: Between October 2021 and October 2023, 324 patients were screened, and 120 were randomly assigned to NBO+EVT or EVT alone (60 patients per group; intention-to-treat population). The median baseline National Institutes of Health Stroke Scale score was 12 (interquartile range [IQR], 8–15) in the NBO+EVT group and 12 (IQR, 9–16) in the EVT-alone group. The median time from stroke onset to randomization was 10.0 hours (IQR, 7.0–14.4) and 9.9 hours (IQR, 8.4–14.8), respectively. The EVT+NBO group demonstrated a significantly higher rate of early neurological improvement compared with EVT alone (35% versus 19%; adjusted odds ratio, 2.86 [95% CI, 1.12–7.45]). The median infarct volume at 24 to 48 hours was significantly smaller in the EVT+NBO group (20.5 [IQR, 13.6–31.8] mL versus 32.3 [IQR, 22.7–44.5] mL; P =0.001). At 90 days, the modified Rankin Scale distribution numerically favored NBO+EVT but was not statistically significant (median modified Rankin Scale, 2 [IQR, 1–3] versus 3 [IQR, 1–4]; adjusted common odds ratio, 1.52 [95% CI, 0.87–2.63]). Mortality, symptomatic intracranial hemorrhage, early neurological deterioration, and recurrent stroke did not differ between groups. CONCLUSIONS: In patients with acute ischemic stroke treated 6 to 24 hours after onset, adjunctive NBO with EVT was safe and improved early neurological outcomes and infarct volume, supporting further evaluation in larger trials. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05128422.