Normobaric hyperoxia combined with endovascular treatment for acute ischaemic stroke in China (OPENS-2 trial): a multicentre, randomised, single-blind, sham-controlled trial

Abstract

Background: Endovascular treatment improves the recanalisation rate for patients with acute ischaemic stroke; however, even with endovascular treatment, approximately half of patients do not have a favourable functional outcome. We aimed to evaluate the effect of normobaric hyperoxia combined with endovascular treatment on functional outcomes up to 90 days after treatment in patients who had an acute ischaemic stroke with large-vessel occlusion.

Methods: In this multicentre, randomised, single-blind, sham-controlled trial, patients aged 18-80 years presenting within 6 h of acute ischaemic stroke attributed to large-vessel occlusion in anterior circulation, who were candidates for endovascular treatment, were recruited from 26 comprehensive stroke centres in China. Eligible patients were randomly assigned (1:1), with an Interactive Web Response System on the basis of a minimisation process to balance assignment at each participating site both overall and according to age, sex, occlusion location, and use of intravenous thrombolytics, to receive either normobaric hyperoxia combined with endovascular treatment or sham normobaric hyperoxia combined with endovascular treatment. Participants and assessors were blinded to treatment assignment. Normobaric hyperoxia treatment involved inhaling 100% oxygen at a flow rate of 10 L/min through a non-rebreather mask for 4 h, or an inspiratory oxygen fraction (FiO₂) of 1·0 in participants for whom intubation was necessary. Sham treatment was 100% oxygen delivered at a flow rate of 1 L/min or an FiO₂ of 0·3. The primary outcome was the comparison of the ordinal scores on the modified Rankin Scale (mRS) at 90 days assessed in the intention-to-treat population (including all patients randomly assigned to treatment). Safety was assessed in all patients who received any oxygen therapy. This trial is registered with ClinicalTrials.gov, NCT04681651, and is now complete.

Findings: Between April 22, 2021, and Feb 5, 2023, 473 patients were screened, of whom 282 were randomly assigned to either normobaric hyperoxia plus endovascular treatment (n=140) or sham normobaric hyperoxia plus endovascular treatment (n=142; intention-to-treat population). The median age was 65 years (IQR 57-71), 75 (27%) of 282 participants were female, 207 (73%) were male, and 282 (100%) of participants were of Chinese Han ethnicity. At 90 days, the median score on the mRS for the normobaric hyperoxia group was 2 (IQR 1-4) and it was 3 (1-4) in the sham normobaric hyperoxia group (adjusted common odds ratio 1·65 [95% CI 1·09-2·50]; p=0·018). At 90 days, 14 (10%) of 140 patients in the normobaric hyperoxia group and 17 (12%) of 142 in the sham normobaric hyperoxia group died (adjusted risk difference -0·02 [95% CI -0·09 to 0·06]) and 28 (20%) and 33 (23%) had serious adverse events (adjusted risk difference -0·03 [-0·12 to 0·07]).

Interpretation: In patients with acute ischaemic stroke caused by large-vessel occlusion in the anterior circulation who were candidates for endovascular treatment, normobaric hyperoxia yielded superior functional outcomes at 90 days compared with the sham normobaric hyperoxia, without raising safety concerns.

Funding: Beijing Municipal Education Commission, Beijing Municipal Finance Bureau, and National Natural Science Foundation of China.