Normobaric Oxygen Therapy in Acute Ischemic Stroke Trial

Ischemic Stroke Clinical Trial

Official title:

Clinical Trial of Normobaric Oxygen Therapy in Acute Ischemic Stroke

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00414726
• Other study ID #: R01NS051412
• Secondary ID: P50NS051343
• Status: Terminated
• Phase: Phase 2
• First received: December 21, 2006
• Last updated: October 18, 2017
• Start date: January 2007
• Est. completion date: June 2009

Study information

• Verified date: October 2017
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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. 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 85
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cerebral Infarction
• Ischemia
• Ischemic Stroke
• Stroke

Intervention

Drug:
• NBO (Normobaric Oxygen)
High-flow oxygen delivered via a facemask. A total of 240 individuals with acute ischemic stroke will be randomized 1:1 to receive either room air or oxygen administered at 30-45 L/min via a simple facemask for 8 hours.
• Room Air
Room Air delivered via a facemask. A total of 240 individuals with acute ischemic stroke will be randomized 1:1 to receive either room air or oxygen administered at 30-45 L/min via a simple facemask for 8 hours.

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital, 75 Francis Street	Boston	Massachusetts
United States	Massachusetts General Hospital, ACC-729C	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

References & Publications (6)

Fujiwara N, Murata Y, Arai K, Egi Y, Lu J, Wu O, Singhal AB, Lo EH. Combination therapy with normobaric oxygen (NBO) plus thrombolysis in experimental ischemic stroke. BMC Neurosci. 2009 Jul 15;10:79. doi: 10.1186/1471-2202-10-79. — View Citation

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

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. — View Citation

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. — View Citation

Singhal AB, Ratai E, Benner T, Vangel M, Lee V, Koroshetz WJ, Schaefer PW, Sorensen AG, Gonzalez RG. Magnetic resonance spectroscopy study of oxygen therapy in ischemic stroke. Stroke. 2007 Oct;38(10):2851-4. Epub 2007 Aug 30. — View Citation

Singhal AB. Oxygen therapy in stroke: past, present, and future. Int J Stroke. 2006 Nov;1(4):191-200. doi: 10.1111/j.1747-4949.2006.00058.x. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary Safety Outcome Measure is a Comparison of the Change in National Institutes of Health Stroke Scale (NIHSS) Scores From Baseline to 24 Hours (After Therapy) in the Two Groups.	The NIHSS score ranges from 0 (best score) to 42 (worst score).	24 hours
Primary	Primary Efficacy Outcome Measure is a Comparison of the Change in National Institutes of Health Stroke Scale (NIHSS) Scores From Baseline to 4 Hours (During Therapy) in the Two Groups.	The NIHSS score ranges from 0 (best score) to 42 (worst score).	4 hours after starting treatment

External Links

•   Specialized Program of Translational Research in Acute Stroke website