Adjuvant Cerebroprotection Using Normobaric Hyperoxia in Pre-hospital Patients with Suspected Stroke (AN-O2-EMS)

The primary objective of this study is to determine the efficacy and safety of inhaled normobaric hyperoxia therapy (NBO) beginning in the pre-hospital setting in patients with suspected acute cerebral ischemia (ACI) due to large vessel occlusion presenting within 6 hours of symptom onset.

Study Overview

• Status: Not yet recruiting
• Conditions: Stroke Acute
• Intervention / Treatment: Other: NBO; Other: Control

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 Type: Interventional
• Enrollment (Estimated): 1000
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Lan Liu, PhD; Phone Number: 8683911991; Email: liulan1815@outlook.com
• Study Contact Backup: Name: Wenbo Hu, MD; Phone Number: 8683911991; Email: huwenbo0050@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100053
      • Xuanwu Hospital, Capital Medical University
      • Contact: Wenbo Hu, MD; Phone Number: 010-83911991; Email: huwenbo0050@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18 to 80 years old;
• 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);
• No prior stroke;
• The time from stroke onset/last seen well to randomization is within 6 hours;
• Paramedic-obtained FAST-ED score >= 3 (The enrollment of patients with a FAST-ED score of 3 is prespecified to constitute no more than 10% of the total study population);
• No significant pre-stroke disability (pre-stroke mRS 0-1);
• Signed informed consent from the patient or the legally authorized representative (LAR).

Exclusion Criteria:

• Endotracheal intubation in the field (prior to consent);
• Respiratory rate <= 10 or >= 30 breaths per minute;
• Oxygen-dependence at baseline to maintain SaO2 > 95%;
• Known history of severe chronic obstructive pulmonary disease (FEV1 less than 1.0), New York Heart Association (NYHA) Heart Failure Class III, acute pulmonary infection or aspiration pneumonia, prior to enrollment;
• Seizure at stroke onset;
• Exhibiting symptoms of vomiting, severe headache, or unconscious;
• Known pregnancy: women of childbearing age (18 to 44 years old according to the CDC's Division of Reproductive Health) will be asked about their pregnancy status.
• Participating in another clinical trial, or completed participation within prior 30 days;
• Receiving other neuroprotective agent (e.g., edaravone dexborneol, n-butylphthalide);
• Life expectancy < 90 days due to comorbidities;
• Unlikely to complete the 90-day follow-up visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NBO; NBO will be conducted with inhalation of 100% oxygen. NBO will be used in conjunction with best medical practice.	Other: NBO; NBO will be conducted with inhalation of 100% oxygen.
Other: Control; Best medical treatment	Other: Control; Best medical care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Level of disability at 90 days measured by modified Rankin scale (mRS) score	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	90 days after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	90 days after randomization
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	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.	90 days after randomization
National Institutes of Health Stroke Scale (NIHSS) obtained obtained upon Endovascular Thrombectomy (EVT) site arrival	The National Institutes of Health Stroke Scale (NIHSS) ranges from 0 to 42 points, with higher scores indicating worse neurological deficits. This is obtained upon Endovascular Thrombectomy (EVT) site arrival.	Day 0
National Institutes of Health Stroke Scale (NIHSS) obtained at 24 hours	The National Institutes of Health Stroke Scale (NIHSS) ranges from 0 to 42 points, with higher scores indicating worse neurological deficits.	24 hours after randomization
ASPECTS on admission head CT	Alberta Stroke Program Early CT (ASPECT) score ranges from 0 to 10, with 10 being normal and 0 indicating complete MCA infarction obtained upon Endovascular Thrombectomy (EVT) site arrival.	Day 0
NCCT infarct volume at 24 hours in patients undergoing thrombolysis or EVT (standard of care)	Infarct volume measured by NCCT	24 hours after randomization
Proportion of patients with elevated troponin level upon EVT hospital arrival	0-100%. This measure is obtained upon Endovascular Thrombectomy (EVT) site arrival.	Day 0

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serious adverse events/Adverse events	total number of serious adverse events/adverse events reported during follow-up, according to standard definitions	Through study completion
Symptomatic intracranial hemorrhage	Number of cases of symptomatic intracerebral hemorrhage according to standard definition	Up to 36 hours after randomization
Any intracranial hemorrhage	Number of cases of any intracranial hemorrhage according to standard definitions	Up to 36 hours after randomization
Early neurological deterioration	Early neurological deterioration at 24 hours, defined as at least 4-point increase in National Institutes of Health Stroke Scale (NIHSS) score from baseline; Larger the increase means worsening of outcomes. The Increase of score range from 0 to 42.	24 hours after randomization
Heart rate at the end of oxygen therapy	Vital signs at the end of oxygen therapy	Day 0
Respiratory rate at the end of oxygen therapy	Vital signs at the end of oxygen therapy	Day 0
Systolic blood pressure at the end of oxygen therapy	Vital signs at the end of oxygen therapy	Day 0
Diastolic blood pressure at the end of oxygen therapy	Vital signs at the end of oxygen therapy	Day 0
Oxygen saturation at the end of oxygen therapy	Vital signs at the end of oxygen therapy	Day 0

Collaborators and Investigators

• Sponsor: Capital Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2025
• Primary Completion (Estimated): January 30, 2028
• Study Completion (Estimated): January 30, 2028

Study Registration Dates

• First Submitted: January 21, 2025
• First Submitted That Met QC Criteria: January 24, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 24, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Ischemic stroke
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Signs and Symptoms, Respiratory; Stroke; Hyperoxia
• Other Study ID Numbers: AN-O2-EMS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No