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

Capital Medical University282 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

282

Conditions

Stroke, Acute Neuroprotection

Interventions

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.

Sham Normobaric HyperoxiaDRUG

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%；

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: General inclusion criteria 1. It conforms to the indications for endovascular thrombectomy 2. 18 ≦ Age ≦ 80 years old. 3. The clinical symptoms and signs are consistent with acute anterior circulation large vessel occlusion; 10≤NIHSS≤20； 4. (Level of consciousness) NIHSS score 0 or 1; 5. The time from onset to randomization is within 6 hours of onset; 6. The mRS score before stroke is 0-1; 7. 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 1. Rapid neurological function improvement, NIHSS score less than 10 points, or evidence of vessel recanalization prior to randomization; 2. Seizures at stroke onset; 3. Intracranial hemorrhage; 4. Symptoms suggestive of subarachnoid hemorrhage, even if CT scan was normal; 5. Known hemorrhagic diathesis, coagulation factor deficiency, or on anticoagulant therapy with INR \> 3.0 or PTT \> 3 times normal; 6. Platelet count of less than 100,000 per cubic millimeter; 7. Severe hepatic or renal dysfunction; 8. Severe, sustained hypertension (Systolic Blood Pressure \>185 mmHg or Diastolic Blood Pressure \>110 mmHg) 9. Baseline blood glucose of \<50mg/dL (2.78 mmol) or \>400mg/dL (22.20 mmol) 10. Active and chronic obstructive pulmonary disease or acute respiratory distress syndrome; 11. \>3 L/min oxygen required to maintain peripheral arterial oxygen saturation (SaO2) 95% as per current stroke management guidelines; 12. Medically unstable; 13. Life expectancy\<90 days; 14. Patients who could not complete the 90-day follow-up; 15. Evidence of intracranial tumor; 16. Patients with anemia or polycythemia vera or other situations that require urgent oxygen inhalation; 17. Patients with upper gastrointestinal bleeding or nausea or vomiting so that they cannot cooperate with the mask to inhale oxygen. 18. A history of severe allergies to contrast agents; 19. There are any other conditions that are not suitable for endovascular treatment. Image exclusion criteria 1. CTA/MRAshows excessive bending of blood vessels, which may hinder the delivery of the device; 2. Suspected cerebrovascular inflammation based on medical history and CTA/MRA; 3. Suspected aortic dissection based on medical history and CTA/MRA 4. CTA/MRA confirmed multi-vascular area occlusion (such as bilateral anterior circulation or anterior/posterior circulation), or bilateral infarction or multi- regional infarction; 5. CTA/MRAconfirmed moyamoya disease or moyamoya syndrome; 6. CT/MRI confirmed the obvious effect of midline shift 7. CT/MRI confirmed the presence of intracranial tumors

Outcomes

Primary Outcomes

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)

Time frame: 90 ± 14 days after randomization

Secondary Outcomes

Cerebral infarct volume

The infarct volume of cerebral infarct is evaluated by MRI or CT

Time frame: 24-48h after randomization

The proportion of good prognosis

defined by mRS 0-2

Time frame: 90 ± 14 days after randomization

The proportion of functional independence

defined by mRS 0-1

Time frame: 90 ± 14 days after randomization

The proportion of severe disability

defined by mRS 4-6

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 24 ± 6 hours after randomization

Arterial oxygen partial pressure

Laboratory indicators, obtained by arterial blood gas analysis

Time frame: 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)

Time frame: 90 ± 14 days after randomization

EuroQol five dimensions questionnaire（EQ-5D）

The score ranges from 0 to 100, with higher scores indicating optimal health

Time frame: 90 ± 14 days after randomization

Days of hospitalization

Length of stay in hospital

Time frame: 90 ± 14 days after randomization

All-cause mortality

Safety endpoint; the proportion of all patients who died in each group

Time frame: 90 ± 14 days after randomization

Serious adverse events

Safety endpoint; the proportion of serious adverse events in each group

Time frame: 90 ± 14 days after randomization

Stroke-related mortality

Safety endpoint; the proportion of stroke related deaths in each group

Time frame: 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

Time frame: 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

Time frame: 90 ± 14 days after randomization

Symptomatic intracranial hemorrhage

Safety endpoint; according to ECASS II definition

Time frame: 24 ± 6 hours after randomization

Any intracranial hemorrhage

Safety endpoint; the proportion of any intracranial hemorrhage in each group

Time frame: 24 ± 6 hours after randomization

Early neurological deterioration (END)

Safety endpoint; defined as ≥4 point increase in NIHSS score from baseline

Time frame: 24 ± 6 hours after randomization

Systolic and diastolic blood pressure

Safety endpoint; vital signs

Time frame: 24 ± 6 hours after randomization

Heart rate

Safety endpoint; vital signs

Time frame: 24 ± 6 hours after randomization

Respiratory rate

Safety endpoint; vital signs

Time frame: 24 ± 6 hours after randomization

Oxygen saturation

Safety endpoint; vital signs

Time frame: 24 ± 6 hours after randomization

PH of arterial blood gas analysis

Safety endpoint

Time frame: after 4 hours of oxygen therapy

PaCO2 of arterial blood gas analysis

Safety endpoint

Time frame: after 4 hours of oxygen therapy

Lactic acid of arterial blood gas analysis

Safety endpoint

Time frame: after 4 hours of oxygen therapy

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes