Normobaric Hyperoxia Combined With Intravenous Thrombolysis for Acute Ischemic Stroke (OPENS-3)

In this study, cases of acute ischemic stroke who undergo intravenous thrombolysis within 4.5 hours from onset are included. The Normobaric Hyperoxia(NBO) group receive basic intravenous thrombolysis and given 100% oxygen inhalation at a ventilation rate of 10L/ min using a sealed non-ventilating oxygen storage mask and keep giving oxygen for 4 hours. The control group receive basic intravenous thrombolysis and given oxygen inhalation at a ventilation rate of 1L/min using nasal cannula and keep giving oxygen for 4 hours. The investigators aimed to determine the efficacy and safety of Normobaric Hyperoxia combined with intravenous thrombolysis for acute ischemic stroke.

Inclusion criteria

• Age≥18 years;
• The time from onset to randomization is within 4.5 hours of onset;
• The clinical diagnosis is acute ischemic stroke (the criteria followed the Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2018);
• Baseline NIHSS (at the time of randomization) should be ≥5 and ≤25 points;
• Pre-stroke mRS score≤1 points;
• Informed consent from the patient or surrogate.

Exclusion criteria

• Intracranial hemorrhage (including parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/extradural hematoma, etc.);
• Past history of intracranial hemorrhage;
• Rapid neurological function improvement, NIHSS score less than 5 points;
• Presence of proximal arterial occlusion on computed tomographic angiography(CTA)/magnetic resonance angiography(MRA) (e.g., intracranial internal carotid artery(ICA), middle cerebral artery(MCA)-M1, and vertebrobasilar arteries);
• Massive anterior cerebral infarction identified by CT or MRI (ASPECT < 6 or lesions larger than one third of the territory of the middle cerebral artery);
• Intended to proceed endovascular treatment;
• Pregnant women, or planning to become pregnant during the trial;
• A history of severe head trauma or stroke within 3 months;
• A history of intracranial or spinal surgery within 3 months;
• A history of gastrointestinal or urinary bleeding within 3 weeks;
• two weeks of major surgery;
• Arterial puncture was performed at the hemostasis site that was not easily compressed within 1 week;
• Active visceral bleeding;
• Intracranial tumors, large intracranial aneurysms;
• Aortic arch dissection was found;
• 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);
• Oral warfarin anticoagulant with international normalized ratio(INR)>1.7 or prothrombin time(PT)>15 s;
• Heparin treatment was received within 24 h;
• Thrombin inhibitors or factor Xa inhibitors were used within 48 h;
• Propensity for acute bleeding, including platelet counts of less than 100×109/ L or otherwise;
• Hereditary or acquired bleeding constitution;
• Onset with seizures;
• Severe liver and kidney dysfunction;
• Active and chronic obstructive pulmonary disease or acute respiratory distress syndrome;
• 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;
• Life expectancy < 1 year;
• Patients who could not complete the 90-day follow-up;
• Participation in other clinical trials within 3 months prior to screening;
• Unsuitability or participation in this study as judged by the Investigator may result in subjects being exposed to greater risk.