OPENS-2
(2025)Objective
To evaluate the effect of normobaric hyperoxia combined with endovascular treatment on 90-day functional outcomes in patients with acute ischaemic stroke caused by large-vessel occlusion in the anterior circulation.
Study Summary
• Mortality at 90 days was similar: 10% (14/140) NBO vs 12% (17/142) sham (adjusted risk difference -0.02, 95% CI -0.09 to 0.06)
• Serious adverse events were comparable: 20% (28/140) NBO vs 23% (33/142) sham (adjusted risk difference -0.03, 95% CI -0.12 to 0.07)
Intervention
Normobaric hyperoxia: inhalation of 100% oxygen at 10 L/min via non-rebreather mask for 4 hours (or FiO2 1.0 if intubated), administered within 30 minutes of treatment allocation, combined with endovascular treatment.
Inclusion Criteria
Age 18-80 years; acute ischaemic stroke from large-vessel occlusion in internal carotid artery or M1 segment of MCA with <1/3 MCA territory involved on CT/MRI; candidates for endovascular treatment within 6 hours of stroke onset; pre-stroke mRS 0-1; NIHSS 10-20 (initially 10-18); ASPECTS ≥6.
Study Design
Arms: Normobaric hyperoxia + endovascular treatment (n=140) vs Sham normobaric hyperoxia + endovascular treatment (n=142)
Patients per Arm: 140 vs 142
Outcome
• 90-day mortality: 10% NBO vs 12% sham (adjusted risk difference -0.02, 95% CI -0.09 to 0.06)
• Serious adverse events: 20% NBO vs 23% sham (adjusted risk difference -0.03, 95% CI -0.12 to 0.07)
Bottom Line
Adjunctive normobaric hyperoxia (100% O2 at 10 L/min for 4 h) given alongside endovascular treatment produced a significant favorable shift in 90-day mRS distribution (adjusted common OR 1.65, 95% CI 1.09-2.50; p=0.018) without raising mortality or serious adverse event rates, supporting NBO as a low-cost, widely available adjunctive neuroprotective therapy in anterior-circulation LVO stroke.
Major Points
- First completed multicentre randomised trial of normobaric hyperoxia plus endovascular treatment in anterior-circulation LVO stroke
- Significant favorable shift in 90-day mRS distribution with NBO (median mRS 2 vs 3; adjusted common OR 1.65, 95% CI 1.09-2.50; p=0.018)
- No increase in 90-day mortality (10% vs 12%) or serious adverse events (20% vs 23%) with NBO
- Intervention is simple, low-cost, and globally deployable: 100% O2 at 10 L/min via non-rebreather mask for 4 hours
- Trial enrolled exclusively Chinese Han patients; generalizability to other populations needs confirmation
- Inclusion criteria broadened during the trial to NIHSS 10-20 (from 10-18) due to slow COVID-era recruitment
Study Design
- Study Type
- Multicentre, randomised, single-blind, sham-controlled, investigator-initiated trial
- Randomization
- Yes
- Blinding
- Single-blind: participants and outcome assessors blinded; site investigators and neuro-interventionalists not blinded
- Sample Size
- 282
- Follow-up
- 90 days
- Centers
- 26
- Countries
- China
Primary Outcome
Definition: Ordinal score on the modified Rankin Scale (mRS) at 90 days, analysed in the intention-to-treat population
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| Median mRS 3 (IQR 1-4) | Median mRS 2 (IQR 1-4) | 1.65 (1.09-2.50) | 0.018 |
Limitations & Criticisms
- Single-blind design: site investigators and neuro-interventionalists were unblinded to allocation, which could introduce performance bias in procedural management
- Enrolment limited to Chinese Han patients across 26 Chinese centres, limiting generalizability to other populations and health-care systems
- Inclusion criteria were broadened mid-trial (NIHSS 10-18 expanded to 10-20) due to COVID-era recruitment delays
- Sham used 100% O2 at 1 L/min (or FiO2 0.3 if intubated), not true room air, which may not be a fully neutral comparator
- Narrow eligibility (NIHSS 10-20, ASPECTS ≥6, ≤6 h from onset) limits applicability to patients with milder/more severe deficits, larger cores, or later windows
- Secondary outcomes were not adjusted for multiple comparisons, precluding definitive conclusions
Citation
Li W, Lan J, Wei M, et al. Normobaric hyperoxia combined with endovascular treatment for acute ischaemic stroke in China (OPENS-2 trial). Lancet. 2025;405(10477):486-497.