Clinical trial NCT06666764: Normobaric Oxygen in AIS Transferred for EVT
Official title: Adjuvant Normobaric Hyperoxia in Acute Ischemic Stroke Patients Transferred for Thrombectomy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Ischemic Stroke
Keywords: ischemic stroke
cerebral protection
Lead sponsor: Capital Medical University
Sponsor class: OTHER
First posted: 2024-10-31
Enrollment: 1500
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 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Level of disability at 90 days measured by modified Rankin scale (mRS) score
timeFrame: 90 days after randomization
Secondary outcomes:
measure: 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
timeFrame: 90 days after randomization
measure: 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
timeFrame: 90 days after randomization
measure: National Institutes of Health Stroke Scale (NIHSS)
timeFrame: 24 hours after randomization
measure: Early neurological improvement
timeFrame: 24 hours after randomization
measure: Alberta Stroke Program Early CT (ASPECT) score upon the Endovascular Thrombectomy (EVT) sites' admission
timeFrame: Day 0, Endovascular Thrombectomy (EVT) site admission
measure: Change of Infarct volume at 24 hours from baseline
timeFrame: 24 (+/- 12) hours after randomization
measure: EuroQol five dimensions questionnaire（EQ-5D）
timeFrame: 90 days, 1 year after randomization
measure: 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)
timeFrame: Day 5 (or discharge if earlier) after randomization
measure: 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)
timeFrame: Day 5 (or discharge if earlier) after randomization
measure: Spontaneous or IV thrombolysis induced recanalization from baseline to Endovascular Thrombectomy (EVT) site arrival
timeFrame: Day 0, Endovascular Thrombectomy (EVT) site admission
measure: Barthel Index
timeFrame: 90 days after randomization
Other outcomes:
measure: Serious adverse events/Adverse events
timeFrame: Through study completion
measure: Symptomatic intracranial hemorrhage
timeFrame: Up to 36 hours after randomization
measure: Any intracranial hemorrhage
timeFrame: Up to 36 hours after randomization
measure: Early neurological deterioration
timeFrame: 24 hours after randomization
measure: Vital signs
timeFrame: Day 0, at the end of oxygen therapy
Locations:
city: Beijing
country: China
facility: Xuanwu Hospital, Capital Medical University
state: Beijing
city: Qujing
country: China
facility: The First People's Hospital of Qujing
state: Yunnan
Study officials:
References: