Normobaric Hyperoxia With Extended-Window Endovascular Therapy for Acute Ischemic Stroke (OPENS-EXTEND)
Trial statusNot yet recruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorWeifang Medical University
About this 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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
Oxygen (Normobaric Hyperoxia)
DrugNormobaric 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 Hyperoxia
DrugSham 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 Therapy
Procedure/SurgeryEndovascular 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.
Treatment groups
314 Participants
are divided into 2 treatment groupsGroup A: Periprocedural Normobaric Hyperoxia Plus Endovascular TherapyExperimental treatment 2 interventions
Group B: Sham Normobaric Hyperoxia Plus Endovascular TherapySham comparator 2 interventions
Trial outcomes
Primary outcomes
1
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.
Time frame
90 days after randomization, with an allowable visit window of ±14 days2
All-Cause Mortality at 90 Days
The proportion of participants who die from any cause within 90 days after randomization.
Time frame
Within 90 days after randomizationSecondary outcomes
1
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.
Time frame
90 days after randomization, with an allowable visit window of ±14 days2
Excellent Functional Outcome at 90 Days
The proportion of participants with a modified Rankin Scale score of 0 to 1.
Time frame
90 days after randomization, with an allowable visit window of ±14 days3
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
Time frame
90 days after randomization, with an allowable visit window of ±14 days4
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.
Time frame
90 days after randomization, with an allowable visit window of ±14 daysLocations
Sponsors and contacts
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Source ClinicalTrials.gov
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