Normobaric Oxygen Therapy in Acute Ischemic Stroke Trial

Stroke is the third leading cause of death and the leading cause of disability in the United
States. Ischemic stroke is caused by a blockage of blood flow to one or more brain arteries,
usually due to a blood clot. As a result there is a reduced supply of oxygen and other
nutrients leading to permanent brain damage. Normobaric oxygen therapy (NBO, or high-flow
oxygen delivered via a facemask) shows promise as a simple, widely accessible, low-cost
therapy that can prevent stroke-related brain damage and extend the time window for
administering the clot-busting drug t-PA (tissue plasminogen activator), which is the only
acute stroke treatment approved by the Food and Drug Administration.

The primary goal of this trial is to compare the safety and therapeutic efficacy of NBO
(started within 9 hours of symptom onset) to standard medical treatment with Room Air. We aim
to enroll a total of 240 individuals with acute ischemic stroke less than 9 hours after
symptom onset, at the Massachusetts General and Brigham and Women's Hospitals in Boston.
Participants will be randomly selected to receive either room air (RA, control) or NBO
(active treatment) at flow rates of 30-45L/min administered via a face mask for 8 hours.
Neurological function scores and neuroimaging [magnetic resonance imaging (MRI) or computed
tomography (CT) scans] will be obtained before, during, and after therapy until 90 days.

This study is part of the Specialized Program of Translational Research in Acute Stroke
(SPOTRIAS), which allows researchers to enhance and initiate translational research that
ultimately will benefit individuals with stroke.

Inclusion Criteria:

- Age greater than or equal to 18 years.

- Acute ischemic stroke in whom treatment can potentially be started within 9 hours
after symptom onset. If the symptom onset time is unknown, the time of onset will be
defined as the midpoint between the time when the subject was last seen neurologically
intact, and when found to have a neurological deficit.

- National Institutes of Health Stroke Scale (NIHSS) score 4 or greater.

Exclusion Criteria:

- Patients being actively considered for intravenous or intra-arterial thrombolysis will
be excluded.

- Patients likely to have acute stroke intervention such as carotid endarterectomy or
stent or angioplasty, hemicraniectomy, etc.

- Rapidly improving neurological deficits (transient ischemic attack).

- Known history of severe chronic obstructive pulmonary disease (Forced Expiratory Vital
Capacity less than 1.0 or oxygen dependent).

- More than 3 L/min oxygen required to maintain peripheral arterial oxygen saturation
above 92%.

- New York Heart Association Class III heart failure.

- Endotracheal intubation prior to enrollment or impending need for artificial
ventilation.

- Coma (National Institutes of Health Stroke Scale item 1a score of 3).

- Suspected seizure at or after onset of stroke, or a known active seizure disorder.

- Blood glucose below 50 mg/dL or greater than 250 mg/dL prior to enrollment.

- Concurrent severe non-stroke medical illness requiring admission to a non-neurological
intensive care unit

- Expected survival less than 90 days.

- Any condition that might limit neurological assessment or follow-up in the opinion of
the investigator.

- Pre-menopausal women with a positive pregnancy blood test performed at admission.

- Inability to obtain consent from the patient or legally authorized representative.

- Active participation in another intervention study (e.g. investigational drug trial).

- Proven alternate etiology for stroke-like symptoms.