Normobaric Oxygen in AIS Transferred for EVT

Phase 3

Recruiting

• Conditions: Ischemic Stroke

• Registration Number: NCT06666764
• Lead Sponsor: Capital Medical University

Brief Summary

The primary objective of this study is to estimate the efficacy and safety of NBO on 3-month functional outcome after acute ischemic stroke

Detailed Description

Stroke is a leading cause of death and disability globally, with acute ischemic stroke (AIS) patients often benefiting from intravenous thrombolysis and endovascular therapies such as mechanical thrombectomy, which have been shown to improve reperfusion rates. However, despite reperfusion, the proportion of patients with large vessel occlusion achieving a favorable functional outcome, defined as a modified Rankin Scale score of 0-2 at 90 days, remains under 50%.

Normobaric hyperoxia (NBO) emerges as a compelling option for cerebral protection. Its neuroprotective mechanisms are thought to include hypoxic tissue rescue, blood-brain barrier preservation, brain edema reduction, neuroinflammation alleviation, mitochondrial function improvement, oxidative stress mitigation, and apoptosis inhibition. NBO's diffusion properties allow it to reach the penumbra before reperfusion, enhancing aerobic metabolism and potentially reducing infarct volume. Its advantages also include low cost, wide availability, and ease of use, making it accessible across various healthcare settings.

Study Timeline

• Study First Submitted: 2024-10-27
• Study First Submitted QC: 2024-10-29
• Study First Posted: 2024-10-31
• Status Verified: 2024-12
• Study Start: 2024-12-13
• Last Update Submitted: 2024-12-13
• Last Update Posted: 2024-12-17
• Primary Completion: 2027-10
• Study Completion: 2027-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1500

Inclusion Criteria

1. Age at least 18 years old;
2. Signs and symptoms are consistent with a new acute stroke, with low possibility of stroke mimics (e.g., no sudden coma, prior seizure disorder, suspected hypoglycemia);
3. No prior stroke in the last 3 months;
4. Time from stroke onset (last seen well) to randomization is within 9 hours;
5. (1) Baseline NIHSS score at 6 or more and Intracranial ICA or MCA-M1 or MCA-M2 dominant occlusion, with or without tandem cervical carotid stenosis or tandem cervical occlusion, confirmed by preoperative CTA (or MRA, DSA) and consistent with signs and symptoms; or (2) Baseline NIHSS score at 6 or more with a hyperdense MCA sign on non-contrast CT; or (3) Baseline NIHSS score at 12 or more;
6. NIHSS score 0 or 1 in the section of level of consciousness;
7. No significant pre-stroke disability (pre-stroke mRS 0--1);
8. ASPECTS at least 6 on non-contrast CT;
9. Patient is planned for transfer to a EVT-capable hospital for EVT;
10. Signed informed consent from the patient or the legally authorized representative (LAR).

Exclusion Criteria

1. Known history of severe chronic obstructive pulmonary disease (FEV1 less than 1.0), New York Heart Association (NYHA) Heart Failure Class III or IV, acute pulmonary infection or aspiration pneumonia, prior to enrollment;
2. Respiratory rate <= 10 or >= 30 breaths per minute;
3. Oxygen-dependence at baseline to maintain SaO2 > 95% or intubation at baseline;
4. Seizure at stroke onset;
5. Exhibiting symptoms of vomiting, or severe headache, or unconscious;
6. Rapidly improving neurological deficits or transient ischemic attack prior to consent;
7. Signs and symptoms suggestive of subarachnoid hemorrhage, even if CT scan is normal;
8. Evidence of intracranial tumor (except small meningioma) or arteriovenous malformation;
9. Woman of childbearing potential known to be pregnant or with a positive pregnancy test;
10. Life expectancy < 90 days due to comorbidity;
11. Unlikely to complete the 90-day follow-up;
12. Participating in another clinical treatment trial, or completed participation within prior 30 days;
13. Receiving other cerebral protective agent (e.g., edaravone dexborneol, n-butylphthalide);
14. Evidence of acute intracranial hemorrhage on CT/MRI;
15. Significant mass effect with midline shift, defined as any deviation of midline structures such as the septum pellucidum, is observed on CT/MRI scans.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Level of disability at 90 days measured by modified Rankin scale (mRS) score	90 days after randomization	The original modified Rankin scale (mRS) ranges from 0 to 6, with higher scores indicating a worse outcome; the primary outcome here is 3-month ordinal mRS score with mRS 5 and 6 merged into one category; modified intention-to-treat analysis

Secondary Outcome Measures

Name	Time	Method
Functional independence at 90 days defined as the proportion of patients with a modified Rankin scale (mRS) score of 0-2 at 90-day follow up	90 days after randomization	The original modified Rankin scale (mRS) ranges from 0 to 6, with higher scores indicating a worse outcome. The mRS score is dichotomized to define the functional independence as mRS score of 0-2.
Excellent functional outcome at 90 days, defined as the proportion of patients with a modified Rankin scale (mRS) score of 0-1 at 90-day follow up	90 days after randomization	The original modified Rankin scale (mRS) ranges from 0 to 6, with higher scores indicating a worse outcome. The mRS score is dichotomized to define the excellent functional outcome as mRS score of 0-1.
National Institutes of Health Stroke Scale (NIHSS)	24 hours after randomization	The National Institutes of Health Stroke Scale (NIHSS) ranges from 0 to 42 points, with higher scores indicating worse neurological deficits.
Early neurological improvement	24 hours after randomization	Neurological improvement is defined as a decrease of at least 4-point reduction in NIHSS score at 24 hours of randomization to baseline assessment
Alberta Stroke Program Early CT (ASPECT) score upon the Endovascular Thrombectomy (EVT) sites' admission	Day 0, Endovascular Thrombectomy (EVT) site admission	Alberta Stroke Program Early CT (ASPECT) score ranges from 0 to 10, with 10 being normal and 0 indicating complete MCA infarction
Change of Infarct volume at 24 hours from baseline	24 (+/- 12) hours after randomization
EuroQol five dimensions questionnaire（EQ-5D）	90 days, 1 year after randomization	The score ranges from 0 to 100, with higher scores indicating optimal health
Excellent functional outcome at day 5 (or discharge if earlier) defined as modified ranking scale (mRS) score of 0-1 at day 5 (or discharge if earlier)	Day 5 (or discharge if earlier) after randomization	The original modified ranking scale (mRS) score ranges from 0 to 6, with higher scores indicating a worse outcome. We use the dichotomozed mRS score to define the excellent functional outcome as mRS score of 0-1 at day 5 (or discharge if earlier).
Functional independence at day 5 (or discharge if earlier) defined as modified ranking scale (mRS) score of 0-2 at day 5 (or discharge if earlier)	Day 5 (or discharge if earlier) after randomization	The original modified ranking scale (mRS) score ranges from 0 to 6, with higher scores indicating a worse outcome. We use the dichotomozed mRS score to define the functional independence as mRS score of 0-2 at day 5 (or discharge if earlier).
Spontaneous or IV thrombolysis induced recanalization from baseline to Endovascular Thrombectomy (EVT) site arrival	Day 0, Endovascular Thrombectomy (EVT) site admission	Among patients who have related imaging from both the non-EVT and EVT sites
Barthel Index	90 days after randomization	The Barthel Index is an ordinal disability score of 10 categories (range from 0 to 100, higher values indicate better prognosis)

Trial Locations

Locations (2)

The First People's Hospital of Qujing; 🇨🇳 Qujing, Yunnan, China

Xuanwu Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China