Clinical trial NCT05965193: Normobaric Hyperoxia Combined With Intravenous Thrombolysis for Acute Ischemic Stroke：Longterm Outcome (OPENS-3L)
Official title: Normobaric Hyperoxia Combined With Intravenous Thrombolysis for Acute Ischemic Stroke：Longterm Outcome (OPENS-3L)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Acute Ischemic Stroke
Lead sponsor: Capital Medical University
Sponsor class: OTHER
Collaborators: name: Beijing Friendship Hospital
name: Beijing Shijitan Hospital, Capital Medical University
name: Beijing Tongren Hospital
name: People's Hospital of Beijing Daxing District
name: Tianjin Huanhu Hospital
name: Guizhou Provincial People's Hospital
name: Shandong Provincial Hospital
name: The First Affiliated Hospital of Soochow University
name: The First Affiliated Hospital of Zhengzhou University
name: The Affiliated Hospital of Xuzhou Medical University
name: Jining First People's Hospital
name: Linyi People's Hospital
name: Nanyang Central Hospital
name: Rizhao People's Hospital
name: Zhumadian Central Hospital
name: Second Affiliated Hospital of Nanchang University
name: Affiliated Hospital of Nantong University
name: The Second Hospital of Anhui Medical University
name: Changsha Central Hospital
First posted: 2023-07-28
Enrollment: 1230
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the long-term efficacy and safety of Normobaric Hyperoxia combined with intravenous thrombolysis for acute ischemic stroke.

Detailed 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 long-term effect of Normobaric Hyperoxia combined with intravenous thrombolysis for acute ischemic stroke.

Eligibility criteria: 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 tomography angiography(CTA)/magnetic resonance angiography(MRA) (e.g., intracranial internal carotid artery(ICA), middle cerebral arterial(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 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.

Primary outcomes:
measure: Utility-weighted modified Rankin scale scores
timeFrame: 12 months±14 days after randomization
Secondary outcomes:
measure: Cerebral infarct volume
timeFrame: 24-48hours after randomization
measure: modified Rankin Scale (mRS) score
timeFrame: 12 months±14 days after randomization
measure: Good functional outcome
timeFrame: 12 months±14 days after randomization
measure: Excellent functional outcome
timeFrame: 6 months±14 days after randomization
measure: Good functional outcome
timeFrame: 6 months±14 days after randomization
measure: modified Rankin Scale (mRS) score
timeFrame: 6 months±14 days after randomization
measure: Scores assessed by National Institutes of Health Stroke Scale(NIHSS)
timeFrame: 4 ± 2 hours, 24 ± 6 hours, 72 ± 24 hours, 7 ± 2 days after randomization
measure: Barthel Index (BI)
timeFrame: 6 months±14 days,12 months±14 days after randomization
measure: EuroQol five dimensions questionnaire（EQ-5D）
timeFrame: 6 months±14 days,12 months±14 days after randomization
measure: Stroke-related mortality
timeFrame: 12 months±14 days after randomization
measure: All-cause mortality
timeFrame: 12 months±14 days after randomization
measure: Symptomatic intracranial hemorrhage
timeFrame: 24 ± 6 hours after randomization
measure: Asymptomatic intracranial hemorrhage
timeFrame: 24 ± 6 hours after randomization
measure: PH2 intracranial hemorrhage
timeFrame: 24 ± 6 hours after randomization
measure: Adverse events/serious adverse events
timeFrame: 24 ± 12 hours, 7 ± 2 days, 90± 7 days, 6 months±14 days,12 months±14 days after randomization
measure: Excellent functional outcome
timeFrame: 12 months±14 days after randomization
Other outcomes:
Locations:
city: Beijing
country: China
facility: Xuan Wu Hospital，Capital Medical University
state: Beijing
Study officials:
References: