Stroke, AcutePhase 3NCT07717216
Normobaric Hyperoxia With Extended-Window Endovascular Therapy for Acute Ischemic Stroke (OPENS-EXTEND)
A Phase 3 study testing Oxygen (Normobaric Hyperoxia) and Endovascular Therapy in people with Stroke, Acute and Neuroprotection, run by Weifang Medical University.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stroke, Acute, Neuroprotection, Normobaric Hyperoxia
- What is being tested?
- Oxygen (Normobaric Hyperoxia) and Endovascular Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 314 participants
- Where
- No sites listed yet
- Study dates
- 1 Sep 2026to 1 Sep 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 years or older.
- 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.
- Pre-stroke modified Rankin Scale (mRS) score of 0 or 1.
- Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 6 or greater on baseline non-contrast computed tomography or diffusion-weighted magnetic resonance imaging.
- Eligible for endovascular therapy according to current guideline-recommended clinical practice and the judgment of the treating stroke team and neurointerventional team.
- 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.
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- 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.
- Baseline level of consciousness score on item 1a of the NIHSS is 0 or 1.
- Written informed consent has been obtained from the participant or the participant's legally authorized representative.
Who cannot join
- General Exclusion Criteria
- 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.
- 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.
- 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.
- Platelet count below 100 × 10⁹/L.
- 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.
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- 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.
- 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.
- Persistent systolic blood pressure above 185 mmHg or diastolic blood pressure above 110 mmHg despite appropriate antihypertensive treatment.
- Life expectancy of less than 90 days because of a pre-existing disease or other underlying medical condition.
- Known pregnancy.
- 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.
- 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.
- 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.
- 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.
- Active gastrointestinal bleeding.
- 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.
- Current participation in another interventional clinical trial that may interfere with the study intervention, safety assessment, or evaluation of study outcomes.
- 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
- 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.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Efficacy and Safety of Periprocedural Normobaric Hyperoxia With Endovascular Therapy for Acute Ischemic Stroke 6-24 Hours After Last Known Well: A Multicenter Randomized Sham-Controlled Phase 3 Trial
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.
Read the detailed description
Successful reperfusion after endovascular therapy (EVT) does not always result in favorable functional outcomes in patients with acute ischemic stroke. Infarct growth before reperfusion and ischemia-reperfusion injury after recanalization may contribute to poor outcomes. Normobaric hyperoxia (NBO) may preserve salvageable ischemic brain tissue by increasing oxygen delivery to the ischemic penumbra, delaying infarct growth, and reducing blood-brain barrier injury. Previous studies have suggested potential benefits of periprocedural NBO in patients undergoing EVT within 6 hours; however, its efficacy and safety in the 6- to 24-hour treatment window remain uncertain.
OPENS-EXTEND is a prospective, multicenter, randomized, sham-controlled, phase 3 clinical trial. A total of 314 participants will be randomly assigned in a 1:1 ratio to receive NBO plus EVT or sham NBO plus EVT. Eligible participants will have acute anterior-circulation ischemic stroke caused by an internal carotid artery or middle cerebral artery M1-segment occlusion, an NIHSS score of at least 10, an ASPECTS of at least 6, a pre-stroke modified Rankin Scale score of 0 or 1, and imaging evidence of salvageable ischemic brain tissue. Randomization will occur 6 to 24 hours after the participant was last known well.
All participants will undergo EVT as soon as possible according to current guideline-recommended practice and will receive standard medical care. Randomization and initiation of the study intervention must not cause an avoidable delay in EVT.
Participants in the experimental group will receive 100% medical oxygen through a non-rebreather mask at 10 L/min for 4 hours, initiated within 30 minutes after randomization and covering the periods before, during, and after EVT. For participants requiring endotracheal intubation for airway protection, procedural sedation, or general anesthesia, NBO will be delivered through mechanical ventilation, with FiO₂ initially set and targeted at 1.0. If clinically necessary, FiO₂ may be reduced but should be maintained at 0.80 or greater whenever feasible.
Participants in the sham-control group will wear the same mask model. The respiratory indicator and the green membrane covering the opposite side valve will be removed, allowing ambient air to enter through both open lateral ports. Medical oxygen will be delivered at a nominal flow rate of 1 L/min for 4 hours. For intubated participants, FiO₂ will initially be set at 0.30 and may be increased when clinically necessary, but should remain at 0.40 or lower whenever feasible.
Peripheral oxygen saturation will be continuously monitored. Oxygen flow or FiO₂ may be adjusted to maintain SpO₂ above 94% or to protect participant safety. All adjustments, interruptions, rescue oxygen therapy, and premature discontinuations will be documented.
Participants and clinical outcome assessors will be masked to treatment assignment. Personnel administering the intervention, neurointerventionalists, anesthesiologists, and other staff requiring knowledge of oxygen settings will not be masked. The independent clinical event committee and imaging core laboratory will remain masked.
The primary efficacy outcome is the distribution of modified Rankin Scale scores at 90 days, analyzed using an ordinal shift approach. Key secondary outcomes include functional independence at 90 days, early neurological improvement at 24 hours, NIHSS score at 7 days, infarct volume at 24 to 48 hours, and EQ-5D-5L score at 90 days. Key safety outcomes include symptomatic intracranial hemorrhage, any intracranial hemorrhage, and all-cause mortality at 90 days.
The primary analysis will be performed in the intention-to-treat population. The study will evaluate whether periprocedural NBO combined with EVT improves 90-day functional outcomes without increasing clinically important safety risks.
- Being tested
- Oxygen (Normobaric Hyperoxia), Sham Normobaric Hyperoxia, Endovascular Therapy
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oxygen (Normobaric Hyperoxia)Drug
Also called Normobaric Hyperoxia, NBO, Normobaric Oxygen Therapy, High-Concentration Oxygen Therapy
Normobaric hyperoxia will be initiated as soon as possible and within 30 minutes after randomization and will continue for 4 hours. For participants who are not intubated, 100% medical oxygen will be delivered through a non-rebreather mask at a flow rate of 10 L/min.
For participants requiring endotracheal intubation for airway protection, procedural sedation, or general anesthesia, normobaric hyperoxia will be delivered through mechanical ventilation, with FiO₂ initially set and targeted at 1.0 during the 4-hour intervention period. If clinically necessary for participant safety, FiO₂ may be gradually reduced; whenever clinically feasible, FiO₂ should be maintained at 0.8 or greater. All FiO₂ adjustments and their reasons will be documented.
After completion of the 4-hour intervention, normobaric hyperoxia will be discontinued. Supplemental oxygen may subsequently be provided as clinically indicated to maintain peripheral oxygen saturation above 94%.
Sham Normobaric HyperoxiaDrug
Also called Sham Oxygen Therapy, Sham NBO
Sham normobaric hyperoxia will be initiated within 30 minutes after randomization and continued for 4 hours. Non-intubated participants will wear the same mask model as the experimental group. The respiratory indicator and the green membrane covering the opposite side valve will be removed, allowing ambient air to enter through both open lateral ports. Medical oxygen will be delivered at a nominal flow rate of 1 L/min; the intervention is not intended to produce normobaric hyperoxia.
For intubated participants, mechanical ventilation will be provided with FiO₂ initially set at 0.30. Peripheral oxygen saturation will be continuously monitored, and oxygen flow or FiO₂ may be increased as clinically necessary to maintain SpO₂ above 94%. After 4 hours, the sham intervention will be discontinued unless supplemental oxygen is clinically required.
Endovascular TherapyProcedure or surgery
Also called EVT, Endovascular Thrombectomy, Mechanical Thrombectomy
Endovascular therapy will be performed as soon as possible in accordance with current guideline-recommended practice for acute ischemic stroke. The selection of thrombectomy devices, procedural techniques, and anesthesia methods will be determined by the treating neurointerventionalist. All participants will also receive guideline-recommended standard medical treatment and secondary stroke prevention.
| Study group | Role | What they receive |
|---|---|---|
| Periprocedural Normobaric Hyperoxia Plus Endovascular Therapy | Experimental | 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. Receives: Drug: Oxygen (Normobaric Hyperoxia); Procedure: Endovascular Therapy |
| Sham Normobaric Hyperoxia Plus Endovascular Therapy | Sham comparator | 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. Receives: Drug: Sham Normobaric Hyperoxia; Procedure: Endovascular Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Distribution of Modified Rankin Scale Scores at 90 Days
The modified Rankin Scale is a 7-level ordinal scale assessing global disability after stroke, ranging from 0 (no symptoms) to 6 (death). The distribution of scores across all seven categories will be compared between the treatment groups using an ordinal shift analysis and reported as an adjusted common odds ratio with a 95% confidence interval. A common odds ratio greater than 1 will indicate a shift toward better functional outcomes in the NBO group.
Measured: 90 days after randomization, with an allowable visit window of ±14 days
All-Cause Mortality at 90 Days
The proportion of participants who die from any cause within 90 days after randomization.
Measured: Within 90 days after randomization
Secondary outcomes (17)
Functional Independence at 90 Days
The proportion of participants with a modified Rankin Scale score of 0 to 2. A score of 0 to 2 indicates functional independence.
Measured: 90 days after randomization, with an allowable visit window of ±14 days
Excellent Functional Outcome at 90 Days
The proportion of participants with a modified Rankin Scale score of 0 to 1.
Measured: 90 days after randomization, with an allowable visit window of ±14 days
Modified Rankin Scale Score of 0 to 3 at 90 Days
The proportion of participants with a modified Rankin Scale score of 0 to 3
Measured: 90 days after randomization, with an allowable visit window of ±14 days
Barthel Index Score at 90 Days
The Barthel Index assesses independence in activities of daily living. The total score ranges from 0 to 100, with higher scores indicating greater functional independence.
Measured: 90 days after randomization, with an allowable visit window of ±14 days
EuroQol five dimensions questionnaire at 90 Days
The score ranges from 0 to 100, with 100 indicating optimal health
Measured: 90 days after randomization, with an allowable visit window of ±14 days
National Institutes of Health Stroke Scale Score
Neurological impairment will be assessed using the National Institutes of Health Stroke Scale. The total score ranges from 0 to 42, with higher scores indicating greater neurological impairment. Scores at each time point will be analyzed separately.
Measured: 24 hours and 7 days after randomization
Early Neurological Improvement at 24 Hours
The proportion of participants with early neurological improvement, defined as a reduction of at least 30% in the National Institutes of Health Stroke Scale score from baseline to 24 hours after randomization.
Measured: 24 hours after randomization
Length of Index Hospital Stay
The total number of days from admission for the index stroke to discharge from the hospital.
Measured: From index hospital admission to hospital discharge, anticipated within 30 days
Infarct Volume at 24 to 48 Hours
Final cerebral infarct volume, measured in milliliters using diffusion-weighted magnetic resonance imaging and assessed by the blinded imaging core laboratory.
Measured: 24 to 48 hours after randomization
Infarct Core Growth Ratio
The infarct core growth ratio will be calculated as the infarct volume measured on diffusion-weighted magnetic resonance imaging at 24 to 48 hours divided by the baseline ischemic core volume. A higher ratio indicates greater infarct growth.
Measured: Baseline and 24 to 48 hours after randomization
Successful Reperfusion at the End of Endovascular Therapy
The proportion of participants achieving successful reperfusion, defined as an expanded Treatment in Cerebral Ischemia grade of 2b, 2c, or 3, as assessed by the blinded imaging core laboratory.
Measured: Immediately after completion of endovascular therapy
Symptomatic Intracranial Hemorrhage
The proportion of participants with symptomatic intracranial hemorrhage according to the ECASS III definition, defined as imaging-confirmed intracranial hemorrhage associated with an increase of at least 4 points in the National Institutes of Health Stroke Scale score.
Measured: Within 24 to 48 hours after randomization
Any Intracranial Hemorrhage Within 24 Hours
The proportion of participants with any intracranial hemorrhage detected by follow-up computed tomography or magnetic resonance imaging, regardless of neurological deterioration.
Measured: Within 24 hours after randomization
Early Neurological Deterioration
The proportion of participants with early neurological deterioration, defined as an increase of at least 4 points in the National Institutes of Health Stroke Scale score compared with baseline.
Measured: Within 24 to 48 hours after randomization
Stroke-Related Mortality at 90 Days
The proportion of participants who die from the index stroke or its direct neurological complications within 90 days after randomization. The cause of death will be adjudicated by an independent clinical event committee masked to treatment assignment.
Measured: Within 90 days after randomization
Incidence of Adverse Events
he proportion of participants experiencing at least one adverse event during the first 7 days after randomization. Prespecified events include oxygen-related adverse events, pulmonary infection, deep-vein thrombosis, procedural complications, vessel reocclusion, and other clinically significant events.
Measured: Within 7 days after randomization
Incidence of Serious Adverse Events
The proportion of participants experiencing at least one serious adverse event according to the protocol-defined seriousness criteria.
Measured: Within 7 days after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2026
- Study start1 Sep 2026 (estimated)
- Primary completion1 Sep 2029 (estimated)
- Study completion1 Sep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stroke, AcuteStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 314 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Weifang Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Weili Li, Weifang Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07717216
- Sponsor's protocol ID
- OPENS-EXTEND
- Status last verified
- Jul 2026
- First submitted
- 14 Jul 2026
- Last updated
- 21 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Periprocedural Normobaric Hyperoxia With Endovascular Therapy for Acute Ischemic Stroke 6-24 Hours After Last Known Well: A Multicenter Randomized Sham-Controlled Phase 3 Trial
- ClinicalTrials.gov ID
- NCT07717216
- Acronym / sponsor ID
- OPENS-EXTEND
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 314 participants (estimated)
- Lead sponsor
- Weifang Medical UniversityUniversity, hospital or other
- Study start
- 1 Sep 2026 (estimated)
- Primary completion
- 1 Sep 2029 (estimated)
- Study completion
- 1 Sep 2029 (estimated)
- First posted
- 21 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Successful reperfusion after endovascular therapy (EVT) does not always result in favorable functional outcomes in patients with acute ischemic stroke. Infarct growth before reperfusion and ischemia-reperfusion injury after recanalization may contribute to poor outcomes. Normobaric hyperoxia (NBO) may preserve salvageable ischemic brain tissue by increasing oxygen delivery to the ischemic penumbra, delaying infarct growth, and reducing blood-brain barrier injury. Previous studies have suggested potential benefits of periprocedural NBO in patients undergoing EVT within 6 hours; however, its efficacy and safety in the 6- to 24-hour treatment window remain uncertain.
OPENS-EXTEND is a prospective, multicenter, randomized, sham-controlled, phase 3 clinical trial. A total of 314 participants will be randomly assigned in a 1:1 ratio to receive NBO plus EVT or sham NBO plus EVT. Eligible participants will have acute anterior-circulation ischemic stroke caused by an internal carotid artery or middle cerebral artery M1-segment occlusion, an NIHSS score of at least 10, an ASPECTS of at least 6, a pre-stroke modified Rankin Scale score of 0 or 1, and imaging evidence of salvageable ischemic brain tissue. Randomization will occur 6 to 24 hours after the participant was last known well.
All participants will undergo EVT as soon as possible according to current guideline-recommended practice and will receive standard medical care. Randomization and initiation of the study intervention must not cause an avoidable delay in EVT.
Participants in the experimental group will receive 100% medical oxygen through a non-rebreather mask at 10 L/min for 4 hours, initiated within 30 minutes after randomization and covering the periods before, during, and after EVT. For participants requiring endotracheal intubation for airway protection, procedural sedation, or general anesthesia, NBO will be delivered through mechanical ventilation, with FiO₂ initially set and targeted at 1.0. If clinically necessary, FiO₂ may be reduced but should be maintained at 0.80 or greater whenever feasible.
Participants in the sham-control group will wear the same mask model. The respiratory indicator and the green membrane covering the opposite side valve will be removed, allowing ambient air to enter through both open lateral ports. Medical oxygen will be delivered at a nominal flow rate of 1 L/min for 4 hours. For intubated participants, FiO₂ will initially be set at 0.30 and may be increased when clinically necessary, but should remain at 0.40 or lower whenever feasible.
Peripheral oxygen saturation will be continuously monitored. Oxygen flow or FiO₂ may be adjusted to maintain SpO₂ above 94% or to protect participant safety. All adjustments, interruptions, rescue oxygen therapy, and premature discontinuations will be documented.
Participants and clinical outcome assessors will be masked to treatment assignment. Personnel administering the intervention, neurointerventionalists, anesthesiologists, and other staff requiring knowledge of oxygen settings will not be masked. The independent clinical event committee and imaging core laboratory will remain masked.
The primary efficacy outcome is the distribution of modified Rankin Scale scores at 90 days, analyzed using an ordinal shift approach. Key secondary outcomes include functional independence at 90 days, early neurological improvement at 24 hours, NIHSS score at 7 days, infarct volume at 24 to 48 hours, and EQ-5D-5L score at 90 days. Key safety outcomes include symptomatic intracranial hemorrhage, any intracranial hemorrhage, and all-cause mortality at 90 days.
The primary analysis will be performed in the intention-to-treat population. The study will evaluate whether periprocedural NBO combined with EVT improves 90-day functional outcomes without increasing clinically important safety risks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Periprocedural Normobaric Hyperoxia Plus Endovascular Therapy | Experimental | Drug: Oxygen (Normobaric Hyperoxia), Procedure: Endovascular TherapyParticipants 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. |
| Sham Normobaric Hyperoxia Plus Endovascular Therapy | Sham comparator | Drug: Sham Normobaric Hyperoxia, Procedure: Endovascular TherapyParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age 18 years or older.
- 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.
- Pre-stroke modified Rankin Scale (mRS) score of 0 or 1.
- Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 6 or greater on baseline non-contrast computed tomography or diffusion-weighted magnetic resonance imaging.
- Eligible for endovascular therapy according to current guideline-recommended clinical practice and the judgment of the treating stroke team and neurointerventional team.
Key exclusion criteria (29 listed)
- General Exclusion Criteria
- Imaging Exclusion Criteria
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oxygen (Normobaric Hyperoxia)Also: Normobaric Hyperoxia, NBO, Normobaric Oxygen Therapy, High-Concentration Oxygen TherapyNormobaric hyperoxia will be initiated as soon as possible and within 30 minutes after randomization and will continue for 4 hours. For participants who are not intubated, 100% medical oxygen will be delivered through a non-rebreather mask at a flow rate of 10 L/min. For participants requiring endotracheal intubation for airway protection, procedural sedation, or general anesthesia, normobaric hyperoxia will be delivered through mechanical ventilation, with FiO₂ initially set and targeted at 1.0 during the 4-hour intervention period. If clinically necessary for participant safety, FiO₂ may be gradually reduced; whenever clinically feasible, FiO₂ should be maintained at 0.8 or greater. All FiO₂ adjustments and their reasons will be documented. After completion of the 4-hour intervention, normobaric hyperoxia will be discontinued. Supplemental oxygen may subsequently be provided as clinically indicated to maintain peripheral oxygen saturation above 94%. | Drug | Periprocedural Normobaric Hyperoxia Plus Endovascular Therapy |
| Sham Normobaric HyperoxiaAlso: Sham Oxygen Therapy, Sham NBOSham normobaric hyperoxia will be initiated within 30 minutes after randomization and continued for 4 hours. Non-intubated participants will wear the same mask model as the experimental group. The respiratory indicator and the green membrane covering the opposite side valve will be removed, allowing ambient air to enter through both open lateral ports. Medical oxygen will be delivered at a nominal flow rate of 1 L/min; the intervention is not intended to produce normobaric hyperoxia. For intubated participants, mechanical ventilation will be provided with FiO₂ initially set at 0.30. Peripheral oxygen saturation will be continuously monitored, and oxygen flow or FiO₂ may be increased as clinically necessary to maintain SpO₂ above 94%. After 4 hours, the sham intervention will be discontinued unless supplemental oxygen is clinically required. | Drug | Sham Normobaric Hyperoxia Plus Endovascular Therapy |
| Endovascular TherapyAlso: EVT, Endovascular Thrombectomy, Mechanical ThrombectomyEndovascular therapy will be performed as soon as possible in accordance with current guideline-recommended practice for acute ischemic stroke. The selection of thrombectomy devices, procedural techniques, and anesthesia methods will be determined by the treating neurointerventionalist. All participants will also receive guideline-recommended standard medical treatment and secondary stroke prevention. | Procedure or surgery | Periprocedural Normobaric Hyperoxia Plus Endovascular Therapy, Sham Normobaric Hyperoxia Plus Endovascular Therapy |
Primary outcome
Distribution of Modified Rankin Scale Scores at 90 Days
Time frame: 90 days after randomization, with an allowable visit window of ±14 days
The modified Rankin Scale is a 7-level ordinal scale assessing global disability after stroke, ranging from 0 (no symptoms) to 6 (death). The distribution of scores across all seven categories will be compared between the treatment groups using an ordinal shift analysis and reported as an adjusted common odds ratio with a 95% confidence interval. A common odds ratio greater than 1 will indicate a shift toward better functional outcomes in the NBO group.
All-Cause Mortality at 90 Days
Time frame: Within 90 days after randomization
The proportion of participants who die from any cause within 90 days after randomization.
17 secondary outcomes
Functional Independence at 90 Days
Time frame: 90 days after randomization, with an allowable visit window of ±14 days
Excellent Functional Outcome at 90 Days
Time frame: 90 days after randomization, with an allowable visit window of ±14 days
Modified Rankin Scale Score of 0 to 3 at 90 Days
Time frame: 90 days after randomization, with an allowable visit window of ±14 days
Barthel Index Score at 90 Days
Time frame: 90 days after randomization, with an allowable visit window of ±14 days
EuroQol five dimensions questionnaire at 90 Days
Time frame: 90 days after randomization, with an allowable visit window of ±14 days
National Institutes of Health Stroke Scale Score
Time frame: 24 hours and 7 days after randomization
Early Neurological Improvement at 24 Hours
Time frame: 24 hours after randomization
Length of Index Hospital Stay
Time frame: From index hospital admission to hospital discharge, anticipated within 30 days
Infarct Volume at 24 to 48 Hours
Time frame: 24 to 48 hours after randomization
Infarct Core Growth Ratio
Time frame: Baseline and 24 to 48 hours after randomization
Successful Reperfusion at the End of Endovascular Therapy
Time frame: Immediately after completion of endovascular therapy
Symptomatic Intracranial Hemorrhage
Time frame: Within 24 to 48 hours after randomization
Any Intracranial Hemorrhage Within 24 Hours
Time frame: Within 24 hours after randomization
Early Neurological Deterioration
Time frame: Within 24 to 48 hours after randomization
Stroke-Related Mortality at 90 Days
Time frame: Within 90 days after randomization
Incidence of Adverse Events
Time frame: Within 7 days after randomization
Incidence of Serious Adverse Events
Time frame: Within 7 days after randomization
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Oxygen (Normobaric Hyperoxia) and Endovascular Therapy in people with Stroke, Acute and Neuroprotection, run by Weifang Medical University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 21 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Weili Li, MD (86-0536-8192680, liweili0536@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Distribution of Modified Rankin Scale Scores at 90 Days (time frame: 90 days after randomization, with an allowable visit window of ±14 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2026.