Normobaric Oxygen Therapy in Acute Ischemic Stroke Trial

Condition(s) targeted: Stroke

Intervention: normobaric oxygen therapy (Drug); room air (Other)

Phase: Phase 2

Status: Recruiting

Sponsored by: Massachusetts General Hospital

Official(s) and/or principal investigator(s):
Aneesh Singhal, MD, Principal Investigator, Affiliation: Massachusetts General Hospital
Steven K. Feske, MD, Affiliation: Brigham and Women's Hospital, Site Investigator
Karen Furie, MD, MPH, Affiliation: Massachusetts General Hospital, Site Investigator

Overall contact:
Aneesh B. Singhal, MD, Phone: 617 726 8459, Email: asinghal@partners.org

The purpose of this study is to compare the safety and efficacy of treating individuals with acute ischemic stroke with normobaric oxygen therapy (NBO)——given within 9 hours of symptom onset——to standard medical treatment. This trial will also assess the therapeutic potential of NBO in extending the time window for administering clot-busting stroke treatment, such as tissue plasminogen activator, t-PA.

Official title: Clinical Trial of Normobaric Oxygen Therapy in Acute Ischemic Stroke

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome:

Primary efficacy outcome measure is a comparison of the change in NIHSS scores from baseline to 4 hours (during therapy) in the two groups. The primary neuroimaging outcome measure is a similar comparison of the change in MRI ischemic lesion volumes

Primary safety outcome measure is a comparison of the change in NIHSS scores from baseline to 24 hours (during therapy) in the two groups. The primary neuroimaging outcome measure is a similar comparison of the change in MRI ischemic lesion volumes.

Detailed description: 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. At present the clot-busting drug intravenous tissue plasminogen activator, t-PA, is the only acute stroke treatment approved by the Food and Drug Administration. Unfortunately less than 5 percent of individuals with stroke actually receive t-PA because it has to be administered within 3 hours of stroke onset to be safe and effective. Therefore, it is important to develop new therapies for stroke and strategies that can safely extend the time window for delivering clot-busting drugs.

Normobaric oxygen therapy (NBO)——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 clot-busting drugs.

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. This trial will also determine the potential of NBO in extending the therapeutic time window for administering such drugs as t-PA. A total of 240 individuals with acute ischemic stroke will be enrolled at the Massachusetts General and Brigham and Women's Hospitals in Boston. Participants will be randomly selected to receive either room air or oxygen therapy administered 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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 time that is midway between the time when the subject was last seen neurologically intact, and when found to have a neurological deficit.

- 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, induced hypothermia therapy, etc.

- Rapidly improving neurological deficits (transient ischemic attack). Known history of

severe chronic obstructive pulmonary disease (FEV1 less than 1. 0 or oxygen dependent).

- More than 3 L/min oxygen required to maintain peripheral SaO2 > 92%.

- NYHA class III heart failure.

- Endotracheal intubation prior to enrollment or impending need for artificial

ventilation.

- Coma (NIHSS 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

ICU

- 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 (e. g. initial brain imaging shows

primary intracerebral hemorrhage, subarachnoid hemorrhage, brain tumor, demyelinating disease, etc).

Aneesh B. Singhal, MD, Phone: 617 726 8459, Email: asinghal@partners.org

Massachusetts General Hospital, 175 Cambridge Street, Suite 300, Boston, Massachusetts 02114, United States; Recruiting
Aneesh B. Singhal, MD, Phone: 617-726-8459, Email: asinghal@partners.org

Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, United States; Recruiting
Aneesh B. Singhal, MD, Phone: 617-726-8459, Email: asinghal@partners.org

Specialized Program of Translational Research in Acute Stroke website

Related publications:

Singhal AB, Benner T, Roccatagliata L, Koroshetz WJ, Schaefer PW, Lo EH, Buonanno FS, Gonzalez RG, Sorensen AG. A pilot study of normobaric oxygen therapy in acute ischemic stroke. Stroke. 2005 Apr;36(4):797-802. Epub 2005 Mar 10.

Kim HY, Singhal AB, Lo EH. Normobaric hyperoxia extends the reperfusion window in focal cerebral ischemia. Ann Neurol. 2005 Apr;57(4):571-5.

Singhal AB, Dijkhuizen RM, Rosen BR, Lo EH. Normobaric hyperoxia reduces MRI diffusion abnormalities and infarct size in experimental stroke. Neurology. 2002 Mar 26;58(6):945-52.

Liu S, Liu W, Ding W, Miyake M, Rosenberg GA, Liu KJ. Electron paramagnetic resonance-guided normobaric hyperoxia treatment protects the brain by maintaining penumbral oxygenation in a rat model of transient focal cerebral ischemia. J Cereb Blood Flow Metab. 2006 Oct;26(10):1274-84. Epub 2006 Jan 18.

Henninger N, Fisher M. Normobaric hyperoxia - a promising approach to expand the time window for acute stroke treatment. Cerebrovasc Dis. 2006;21(1-2):134-6. Epub 2005 Dec 21. No abstract available.

Flynn EP, Auer RN. Eubaric hyperoxemia and experimental cerebral infarction. Ann Neurol. 2002 Nov;52(5):566-72.

Starting date: January 2007
Ending date: June 2011
Last updated: December 1, 2008