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

Phase 3

Recruiting

• Conditions: Acute Ischemic Stroke
• Interventions: Procedure: Nasal oxygen; Procedure: Normobaric Hyperoxia; Drug: Intravenous thrombolysis(rt-PA)

• Registration Number: NCT05965687
• Lead Sponsor: Ji Xunming,MD,PhD

Brief Summary

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

Study Timeline

• Study First Submitted: 2023-06-07
• Study First Submitted QC: 2023-07-20
• Study First Posted: 2023-07-28
• Study Start: 2023-08-17
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-26
• Last Update Posted: 2024-03-28
• Primary Completion: 2024-08-30
• Study Completion: 2024-10-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1230

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NBO group	Intravenous thrombolysis(rt-PA)	Normobaric Hyperoxia combined with intravenous thrombolysis
Control group	Nasal oxygen	Nasal oxygen combined with intravenous thrombolysis
Control group	Intravenous thrombolysis(rt-PA)	Nasal oxygen combined with intravenous thrombolysis
NBO group	Normobaric Hyperoxia	Normobaric Hyperoxia combined with intravenous thrombolysis

Primary Outcome Measures

Name	Time	Method
Utility-weighted modified Rankin scale scores	90±7 days after randomization	Utility-weighted modified Rankin scale scores

Secondary Outcome Measures

Name	Time	Method
The proportion of neurological function improvement	24 ± 6 hours after randomization	≥ 4 point reduction in National Institutes of Health Stroke Scale (NIHSS) score from baseline at 24 ± 6 hours after randomization;NIHSS score ranges from 0 to 42, and higher scores mean a worse outcome
Barthel Index (BI)	30 ± 7 days,90 ± 7 days after randomization	The BI is an ordinal disability score of 10 categories (range from 0 to 100, higher values indicate better prognosis)
Days of hospitalization	30 ± 7 days after randomization	Length of stay in hospital
Cerebral infarct volume	24-48hours after randomization	The infarct volume of cerebral infarct is evaluated by MRI
EuroQol five dimensions questionnaire（EQ-5D）	baseline before randomization,7 ± 2 days,30 ± 7 days,90 ± 7 days after randomization	The score ranges from 0 to 100, with higher scores indicating optimal health
Asymptomatic intracranial hemorrhage	24 ± 6 hours after randomization	The incidence of asymptomatic intracranial hemorrhage at 24 ± 6 hours after randomization
Systematic bleeding	24 ± 6 hours after randomization	The incidence of systematic bleeding at 24 ± 6 hours after randomization
Oxygen-related adverse events	90 ± 7 days after randomization	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
Unit costs	7 ± 2 days, 30 ± 7 days,90 ± 7 days after randomization	Unit costs will be attached to resource use, patient-reported and from hospital records after randomization, to obtain a cost per patient over the period of follow-up
Excellent functional outcome	90±7 days after randomization	Proportion of subjects with modified Rankin Scale(mRS) 0-1 at 90±7 days after randomization;mRS score ranges from 0 to 5, and the higher score means a worse outcome
modified rankin scale (mRS) score	90±7 days after randomization	Ordinal distribution of mRS at 90±7 days after randomization;mRS score ranges from 0 to 5, and the higher score means a worse outcome
Scores assessed by National Institutes of Health Stroke Scale(NIHSS)	4 ± 2 hours, 24 ± 6 hours, 72 ± 24 hours, 7 ± 2 days after randomization	Scores on the National Institutes of Health Stroke Scale (NIHSS) range from 0 to 42, with higher scores indicating more severe neurologic deficits
Proportion of subjects with modified rankin scale (mRS) 0-1	30 ± 7 days after randomization	Proportion of subjects with mRS 0-1 at 30±7 days after randomization;mRS score ranges from 0 to 5, and the higher score means a worse outcome
Symptomatic intracranial hemorrhage	24 ± 6 hours after randomization	Proportion of subjects with symptomatic intracranial hemorrhage at 24 ± 6 hours after randomization (defined by ECASSII and ECASS III)
PH2 intracranial hemorrhage	24 ± 6 hours after randomization	The incidence of PH2 intracranial hemorrhage at 24 ± 6 hours after randomization (according to SITS standards)
Any intracranial hemorrhage	24 ± 6 hours after randomization	The incidence of any intracranial hemorrhage at 24 ± 6 hours after randomization
Early neurological deterioration	24 ± 6 hours after randomization	Safety endpoint; defined as ≥4 point increase in National Institutes of Health Stroke Scale (NIHSS) score from baseline;NIHSS score ranges from 0 to 42, and higher scores mean a worse outcome
PaCO2 of arterial blood gas analysis	after 4 hours of oxygen therapy	Safety endpoint
Potential of hydrogen(PH) of arterial blood gas analysis	after 4 hours of oxygen therapy	Safety endpoint
Good functional outcome	90 ± 7 days after randomization	Proportion of subjects with modified rankin scale (mRS) 0-2 at 90±7 days after randomization;mRS score ranges from 0 to 5, and the higher score means a worse outcome
Proportion of subjects with modified rankin scale (mRS) 0-3	90 ± 7 days after randomization	Proportion of subjects with mRS 0-3 at 90±7 days after randomization;mRS score ranges from 0 to 5, and the higher score means a worse outcome
Adverse events/serious adverse events	24 ± 12 hours, 7 ± 2 days, 90± 7 days after randomization	Safety endpoint; the proportion of adverse events/serious adverse events in each group
Systolic and diastolic blood pressure	24 ± 6 hours after randomization	Safety endpoint; vital signs
Stroke-related mortality	90 ± 7 days after randomization	Safety endpoint; the proportion of stroke related deaths in each group
All-cause mortality	90 ± 7 days after randomization	Safety endpoint; the proportion of all patients who died in each group
PaO2 of arterial blood gas analysis	after 4 hours of oxygen therapy	Safety endpoint
Concentration of Lactic acid of arterial blood gas analysis	after 4 hours of oxygen therapy	Safety endpoint
Respiratory rate	24 ± 6 hours after randomization	Safety endpoint; vital signs
Oxygen saturation	24 ± 6 hours after randomization	Safety endpoint; vital signs
Heart rate	24 ± 6 hours after randomization	Safety endpoint; vital signs

Trial Locations

Locations (1)

Xuan Wu Hospital，Capital Medical University; 🇨🇳 Beijing, China