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

Ji Xunming,MD,PhD

Status and phase: Enrolling; Phase 3

Conditions: Acute Ischemic Stroke

Treatments: Procedure: Nasal oxygen; Drug: Intravenous thrombolysis(rt-PA); Procedure: Normobaric Hyperoxia

Study type: Interventional

Funder types: Other

Identifiers

NCT05965687

OPENS-3

Details and patient eligibility

About

The purpose of this study is to determine the efficacy and safety of Normobaric Hyperoxia combined with intravenous thrombolysis for acute ischemic stroke.

Full description

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.

Enrollment: 1,230 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

1. Intracranial hemorrhage (including parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/extradural hematoma, etc.);
2. Past history of intracranial hemorrhage;
3. Rapid neurological function improvement, NIHSS score less than 5 points;
4. 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);
5. 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);
6. Intended to proceed endovascular treatment;
7. Pregnant women, or planning to become pregnant during the trial;
8. A history of severe head trauma or stroke within 3 months;
9. A history of intracranial or spinal surgery within 3 months;
10. A history of gastrointestinal or urinary bleeding within 3 weeks;
11. two weeks of major surgery;
12. Arterial puncture was performed at the hemostasis site that was not easily compressed within 1 week;
13. Active visceral bleeding;
14. Intracranial tumors, large intracranial aneurysms;
15. Aortic arch dissection was found;
16. Severe, sustained hypertension (Systolic Blood Pressure >185 mmHg or Diastolic Blood Pressure >110 mmHg);
17. Baseline blood glucose of <50mg/dL (2.78 mmol) or >400mg/dL (22.20 mmol);
18. Oral warfarin anticoagulant with international normalized ratio(INR)>1.7 or prothrombin time(PT)>15 s;
19. Heparin treatment was received within 24 h;
20. Thrombin inhibitors or factor Xa inhibitors were used within 48 h;
21. Propensity for acute bleeding, including platelet counts of less than 100×109/ L or otherwise;
22. Hereditary or acquired bleeding constitution;
23. Onset with seizures;
24. Severe liver and kidney dysfunction;
25. Active and chronic obstructive pulmonary disease or acute respiratory distress syndrome;
26. Patients with anemia or polycythemia vera or other situations that require urgent oxygen inhalation;
27. Patients with upper gastrointestinal bleeding or nausea or vomiting so that they cannot cooperate with the mask to inhale oxygen;
28. Life expectancy < 1 year;
29. Patients who could not complete the 90-day follow-up;
30. Participation in other clinical trials within 3 months prior to screening;
31. Unsuitability or participation in this study as judged by the Investigator may result in subjects being exposed to greater risk.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

1,230 participants in 2 patient groups, including a placebo group

NBO group

Experimental group

Description:

Normobaric Hyperoxia combined with intravenous thrombolysis

Treatment:

Drug: Intravenous thrombolysis(rt-PA)

Procedure: Normobaric Hyperoxia

Control group

Placebo Comparator group

Description:

Nasal oxygen combined with intravenous thrombolysis

Treatment:

Drug: Intravenous thrombolysis(rt-PA)

Procedure: Nasal oxygen