Normobaric Hyperoxia With Extended-Window Endovascular Therapy for Acute Ischemic Stroke (OPENS-EXTEND)

NCT07717216 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: OPENS-EXTEND
• Study Type: interventional
• Target: 314
• Locations: 0 countries
• Sites: N/A

Brief 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. 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.

Conditions

Stroke, Acute; Neuroprotection; Normobaric Hyperoxia; Endovascular Treatment

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Within 90 days after randomization

Secondary Outcomes (17)

• Functional Independence at 90 Days

  90 days after randomization, with an allowable visit window of ±14 days

• Excellent Functional Outcome at 90 Days

  90 days after randomization, with an allowable visit window of ±14 days

• Modified Rankin Scale Score of 0 to 3 at 90 Days

  90 days after randomization, with an allowable visit window of ±14 days

• Barthel Index Score at 90 Days

  90 days after randomization, with an allowable visit window of ±14 days

• EuroQol five dimensions questionnaire at 90 Days

  90 days after randomization, with an allowable visit window of ±14 days

Study Arms (2)

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.

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.

Drug: Sham Normobaric Hyperoxia; Procedure: Endovascular Therapy

Interventions

Sham Normobaric Hyperoxia DRUG

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.

Also known as: Sham Oxygen Therapy, Sham NBO

Sham Normobaric Hyperoxia Plus Endovascular Therapy

Oxygen (Normobaric Hyperoxia) DRUG

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%.

Also known as: Normobaric Hyperoxia, NBO, Normobaric Oxygen Therapy, High-Concentration Oxygen Therapy

Periprocedural Normobaric Hyperoxia Plus Endovascular Therapy

Endovascular Therapy PROCEDURE

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.

Also known as: EVT, Endovascular Thrombectomy, Mechanical Thrombectomy

Periprocedural Normobaric Hyperoxia Plus Endovascular Therapy; Sham Normobaric Hyperoxia Plus Endovascular Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Weifang Medical University: lead

MeSH Terms

Conditions

Stroke

Interventions

Oxygen

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Chalcogens; Elements; Inorganic Chemicals; Gases

Central Study Contacts

Weili Li, MD

CONTACT

86-0536-8192680; liweili0536@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 14, 2026
• First Posted: July 21, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2029
• Last Updated: July 21, 2026

Record last verified: 2026-07