Treatment Duration on Normobaric Hyperoxia in Acute Ischemic Stroke

Study Overview
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Brief Summary
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Normoxia Hyperoxia (NBO) is a neuroprotective approach that can be implemented early. NBO is simple and non-invasive and can be used at home or in an ambulance to ensure the shortest possible time after cerebral ischemia occurs. The previous study by the investigators suggested that NBO therapy in the early stage of cerebral ischemia has a neuroprotective effect on ischemic brain injury. Although the neuroprotective effect of NBO has been demonstrated, the optimal duration of treatment for NBO to exert neuroprotective effect is still unclear. Therefore, further discussion of the duration of NBO treatment will contribute to the clinical application of NBO and provide a definite theoretical basis for the treatment of cerebral infarction.

Official Title
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The Efficacy and Safety of Normobaric Hyperoxia on Treatment Duration for Acute Ischemic Stroke Patients With Endovascular Treatment

Conditions
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Stroke, Acute, Neuroprotection, Endovascular Treatment

Intervention / Treatment
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* Other: Normobaric Hyperoxia (NBO)
* Other: Low flow oxygen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptoms and signs were consistent with acute anterior circulation stroke, NIHSS score≥6分;Alberta Stroke Program Early CT score (ASPECTS)≥6; Met the indications for endovascular therapy; (Level of consciousness)NIHSS score 0 or 1; MRS score was 0-1 before stroke The time from onset to randomization was within 24 hours; Preoperative CTA or MRA confirmed the presence of large vessel occlusion (internal carotid artery or middle cerebral artery M1, M2 segments); Patients and their families signed informed consent Exclusion Criteria: Rapid neurological function improvement, NIHSS score less than 10 points, or evidence of vessel recanalization prior to randomization; Seizures at stroke onset; Intracranial hemorrhage; Symptoms suggestive of subarachnoid hemorrhage, even if CT scan was normal; Known hemorrhagic diathesis, coagulation factor deficiency, or on anticoagulant therapy with INR > 3.0 or PTT > 3 times normal; Platelet count of less than 100,000 per cubic millimeter; Severe hepatic or renal dysfunction; Severe, sustained hypertension (Systolic Blood Pressure >185 mmHg or Diastolic Blood Pressure >110 mmHg) Baseline blood glucose of <50mg/dL (2.78 mmol) or >400mg/dL (22.20 mmol) Active and chronic obstructive pulmonary disease or acute respiratory distress syndrome; >3 L/min oxygen required to maintain peripheral arterial oxygen saturation (SaO2) 95% as per current stroke management guidelines; Medically unstable; Life expectancy<90 days; Patients who could not complete the 90-day follow-up; Evidence of intracranial tumor; Patients with anemia or polycythemia vera or other situations that require urgent oxygen inhalation; Patients with upper gastrointestinal bleeding or nausea or vomiting so that they cannot cooperate with the mask to inhale oxygen. A history of severe allergies to contrast agents;

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Low flow oxygen group<br>patients were randomized into the Low flow oxygen group and immediately given 100% oxygen inhalation (no more than 30 minutes after admission) at a ventilation rate of 1L/ min using a oxygen storage mask and keep giving oxygen for 4 hours. | Other: Low flow oxygen<br>* immediately given oxygen inhalation at a ventilation rate of 1L/ min using a oxygen storage mask and keep giving oxygen for 4 hours.<br>|
| Experimental: NBO group (2h)<br>patients were randomized into the NBO group (2h) and immediately given 100% oxygen inhalation (no more than 30 minutes after admission) at a ventilation rate of 10L/ min using a oxygen storage mask and keep giving oxygen for 2 hours. | Other: Normobaric Hyperoxia (NBO)<br>* NBO was inhaled as early as possible before revascularization, and inhaled for 1h/2h/4h according to different groups<br>|
| Experimental: NBO group (4h)<br>patients were randomized into the NBO group (4h) and immediately given 100% oxygen inhalation (no more than 30 minutes after admission) at a ventilation rate of 10L/ min using a oxygen storage mask and keep giving oxygen for 4 hours. | Other: Normobaric Hyperoxia (NBO)<br>* NBO was inhaled as early as possible before revascularization, and inhaled for 1h/2h/4h according to different groups<br>|
| Experimental: NBO group (6h)<br>patients were randomized into the NBO group (6h) and immediately given 100% oxygen inhalation (no more than 30 minutes after admission) at a ventilation rate of 10L/ min using a oxygen storage mask and keep giving oxygen for 6 hours. | Other: Normobaric Hyperoxia (NBO)<br>* NBO was inhaled as early as possible before revascularization, and inhaled for 1h/2h/4h according to different groups<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cerebral infarct volume | The infarct volume is evaluated by MRI or CT scan | Within 72 hours after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Scores assessed by National Institutes of Health Stroke Scale(NIHSS) | secondary clinical efficacy endpoint; the NIHSS is a stroke severity score composed of 11 items (range from 0 to 41, higher values indicate more severe deficits) | 24hours, 72hours, day7 after randomization | 
| The proportion of good prognosis | the mRs is an ordinal disability score of 7 categories (0 = no symptoms to 5 = severe disability, and 6 = death;with higher scores indicating more severe disability);The ratio of 0 to 2; | 90 ± 10 days after randomization | 
| neurological function improvement rate | NIHSS score increased by more than 4 points);the NIHSS is a stroke severity score composed of 11 items (range from 0 to 42, higher values indicate more severe deficits); | Time Frame: 24 ± 6 hours | 
| modified Rankin Scale score (mRS) score | secondary clinical efficacy endpoint; the mRs is an ordinal disability score of 7 categories (0=no symptoms to 5=severe disability,and 6=death) | 30 ± 7 days, 90 ± 10 days after randomization; | 
| Vascular recanalization rate | secondary imaging efficacy endpoint; Extended Treatment In Cerebral Ischemia (eTICI)；The eTICI is an ordinal hierarchical scale ranging from 0 to 3, with higher scores indicating better antegrade reperfusion of the previously occluded target artery ischemic territory; eTICI 2B or 3 are defined as successful recanalization; | Time Frame: 4 hours ± 15 minutes | 
| blood biomarkers : occludin(ng/ml), MMP-9(ng/ml), S100B(ng/ml),NSE(ng/ml),GFAP(ng/ml),PGP9.5(ng/ml),etc | Biomarkers for evaluation of BBB damage , brain injury and inflammation,etc: | 24 ± 6 hours, 72 ± 24 hours | 
| Incidence of oxygen-related adverse events | Including Headache, dizziness, nausea, vomiting, chest tightness, shortness of breath, cough,etc; | 24 ± 6 hours, | 
| Incidence of neurologic deterioration; | NIHSS score increased by more than 4 points);the NIHSS is a stroke severity score composed of 11 items (range from 0 to 42, higher values indicate more severe deficits);clinical safety endpoint; | 24 ± 6 hours; | 
| Incidence of Symptomatic Intracerebral Hemorrhage | imaging safety endpoints;Deterioration in NIHSS score of ≥4 points within 24 hours;per ECASS III definition and per Heidelberg bleeding classification | 24± 12 hours hours after randomization | 
| Incidence of any intracranial hemorrhage | imaging safety endpoints;per ECASS III definition and per Heidelberg bleeding classification | 24± 12 hours hours after randomization | 
| all-cause death rate | clinical safety endpoint; Ratio of total deaths from all causes to all enrollments | 90 ± 10 days after randomization | 
| Incidence of adverse events | clinical safety endpoint; | 90 ± 10 days after randomization | 
| Incidence of surgery-related complications | clinical safety endpoint; | 24± 12 hours hours after randomization | 
| stroke related death rate | clinical safety endpoint; Stroke-related deaths as a proportion of all participants | 90 ± 10 days after randomization; | 
| Vital signs:respiration(times/min) | clinical safety endpoint; | 0 hours, 2 hours, 4 hours after randomization; | 
| Vital signs:heart rate: (times/min) | clinical safety endpoint; | 0 hours, 2 hours, 4 hours after randomization; | 
| Vital signs:blood pressure(mmHg) | clinical safety endpoint; | 0 hours, 2 hours, 4 hours after randomization; | 
| Vital signs:oxygen saturation (%) | clinical safety endpoint; | 0 hours, 2 hours, 4 hours after randomization; |