Normobaric Hyperoxia Combined With Endovascular Treatment in Acute Ischemic Stroke (OPENS-2)

Study Overview
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Brief Summary
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The current endovascular treatment has increased the recanalization rate to more than 90%. Even so, the prognosis rate of stroke is still less than 50%. Our previous research confirmed that the neuroprotective effect of Normobaric Hyperoxia (NBO) from multiple perspectives. However, the clinical study on NBO was not satisfactory, which might be due to the absence of vascular recanalization therapy. Therefore, The investigators conducted this RCT study to further explore the Efficacy and safety of NBO combined with endovascular treatment in patients with acute ischemic stroke.

Official Title
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A Randomized Controlled Trial Assessing the Efficacy and Safety of Normobaric Hyperoxia for Acute Ischemic Stroke Patients Undergoing Endovascular Treatment

Conditions
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Stroke, Acute, Neuroprotection

Intervention / Treatment
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* Drug: Normobaric Hyperoxia
* Drug: Sham Normobaric Hyperoxia
* Procedure: Endovascular Thrombectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: General inclusion criteria It conforms to the indications for endovascular thrombectomy 18 ≦ Age ≦ 80 years old. The clinical symptoms and signs are consistent with acute anterior circulation large vessel occlusion; 10≤NIHSS≤20； (Level of consciousness) NIHSS score 0 or 1; The time from onset to randomization is within 6 hours of onset; The mRS score before stroke is 0-1; Patient and family members sign informed consent. Image inclusion criteria 1. Preoperative CT or MR or DSA angiography found large vessel occlusion (internal carotid artery or middle cerebral artery M1 segment) that were consistent with symptoms and signs; 2. ASPECT score ≥ 6 points 3. <1/3 MCA area involvement (confirmed by CT or MRI) Exclusion Criteria: General 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; There are any other conditions that are not suitable for endovascular treatment. Image exclusion criteria CTA/MRAshows excessive bending of blood vessels, which may hinder the delivery of the device; Suspected cerebrovascular inflammation based on medical history and CTA/MRA; Suspected aortic dissection based on medical history and CTA/MRA CTA/MRA confirmed multi-vascular area occlusion (such as bilateral anterior circulation or anterior/posterior circulation), or bilateral infarction or multi- regional infarction; CTA/MRAconfirmed moyamoya disease or moyamoya syndrome; CT/MRI confirmed the obvious effect of midline shift CT/MRI confirmed the presence of intracranial tumors

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NBO group<br>Normobaric Hyperoxia combined with endovascular mechanical thrombectomy | Drug: Normobaric Hyperoxia<br>* Within 6 hours after stroke onset, patients were randomized into the NBO group and immediately given 100% oxygen inhalation (no more than 30 minutes after randomization) at a ventilation rate of 10L/ min using a sealed non-ventilating oxygen storage mask and keep giving oxygen for 4 hours. If the patient needs to be intubated with a ventilator to maintain ventilation, the FiO2 should be set to 1.0.<br>* Other names: NBO;Procedure: Endovascular Thrombectomy<br>* EVT is the international guidelines for the treatment of acute ischemic stroke with lage vessel occlusion.<br>* Other names: EVT;|
| Placebo Comparator: Control group<br>Inhale air placebo plus endovascular mechanical thrombectomy | Drug: Sham Normobaric Hyperoxia<br>* For Sham NBO group, Patients were immediately given oxygen inhalation (no more than 30 minutes after randomization) at a ventilation rate of 1l/min using the same mask and keep giving oxygen for 4 hours. If the patient needs to be intubated with a ventilator to maintain, the FiO2 should be set to 0.3 and gradualy incerased if spO2≤94%；<br>* Other names: Sham NBO;Procedure: Endovascular Thrombectomy<br>* EVT is the international guidelines for the treatment of acute ischemic stroke with lage vessel occlusion.<br>* Other names: EVT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Rankin Scale (mRS) score | the mRs is an ordinal disability score of 7 categories (0=no symptoms to 5=severe disability, and 6=death) | 90 ± 14 days after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cerebral infarct volume | The infarct volume of cerebral infarct is evaluated by MRI or CT | 24-48h after randomization | 
| The proportion of good prognosis | defined by mRS 0-2 | 90 ± 14 days after randomization | 
| The proportion of functional independence | defined by mRS 0-1 | 90 ± 14 days after randomization | 
| The proportion of severe disability | defined by mRS 4-6 | 90 ± 14 days after randomization | 
| Scores assessed by National Institutes of Health Stroke Scale(NIHSS) | Scores on the National Institutes of Health Stroke Scale (NIHSS) range from 0 to 42, with higher scores indicating more severe neurologic deficits | 24 ± 6 hours, 72 ± 24 hours, 7 ± 2 days after randomization | 
| The proportion of neurological function improvement | ≥ 4 point reduction in NIHSS score from baseline | 24 ± 6 hours after randomization | 
| Successful vessel recanalization | Successful vessel recanalization is defined by eTICI 2b/2c/3 on final angiogram. Extended treatment in cerebral ischaemia (eTICI) score range from 0 to 3, with higher scores indicating better reperfusion | Immediately after procedure | 
| Vessel recanalization | Vessel recanalization is evaluated by CTA or MRA and assessed by AOL grades. Arterial Occlusive Lesion (AOL) range from 0 to 3, with higher scores indicating better recanalization | 24 ± 6 hours after randomization | 
| Arterial oxygen partial pressure | Laboratory indicators, obtained by arterial blood gas analysis | after 4 hours of oxygen therapy | 
| Barthel Index (BI) | the BI is an ordinal disability score of 10 categories (range from 0 to 100, higher values indicate better prognosis) | 90 ± 14 days after randomization | 
| EuroQol five dimensions questionnaire（EQ-5D） | The score ranges from 0 to 100, with higher scores indicating optimal health | 90 ± 14 days after randomization | 
| Days of hospitalization | Length of stay in hospital | 90 ± 14 days after randomization | 
| All-cause mortality | Safety endpoint; the proportion of all patients who died in each group | 90 ± 14 days after randomization | 
| Serious adverse events | Safety endpoint; the proportion of serious adverse events in each group | 90 ± 14 days after randomization | 
| Stroke-related mortality | Safety endpoint; the proportion of stroke related deaths in each group | 90 ± 14 days after randomization | 
| Oxygen-related adverse events | Safety endpoint; the proportion of oxygen-related adverse events in each group, including severe lung infection, pneumothorax, atelectasis, respiratory failure, acute respiratory distress syndrome, and cardiopulmonary arrest | 90 ± 14 days after randomization | 
| Adverse events of special interest | Safety endpoint; the proportion of adverse events of special interest in each group, including malignant brain edema, perioperative myocardial infarction, and acute heart failure | 90 ± 14 days after randomization | 
| Symptomatic intracranial hemorrhage | Safety endpoint; according to ECASS II definition | 24 ± 6 hours after randomization | 
| Any intracranial hemorrhage | Safety endpoint; the proportion of any intracranial hemorrhage in each group | 24 ± 6 hours after randomization | 
| Early neurological deterioration (END) | Safety endpoint; defined as ≥4 point increase in NIHSS score from baseline | 24 ± 6 hours after randomization | 
| Systolic and diastolic blood pressure | Safety endpoint; vital signs | 24 ± 6 hours after randomization | 
| Heart rate | Safety endpoint; vital signs | 24 ± 6 hours after randomization | 
| Respiratory rate | Safety endpoint; vital signs | 24 ± 6 hours after randomization | 
| Oxygen saturation | Safety endpoint; vital signs | 24 ± 6 hours after randomization | 
| PH of arterial blood gas analysis | Safety endpoint | after 4 hours of oxygen therapy | 
| PaCO2 of arterial blood gas analysis | Safety endpoint | after 4 hours of oxygen therapy | 
| Lactic acid of arterial blood gas analysis | Safety endpoint | after 4 hours of oxygen therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Normobaric hyperoxia, Endovascular treatment, Acute ischemic stroke