Normobaric Oxygen Therapy in Acute Ischemic Stroke Trial

NCT ID: NCT00414726

Last Updated: 2017-10-20

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

85 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-01-31

Study Completion Date

2009-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Ischemic Stroke

Keywords

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ischemic stroke normobaric oxygen therapy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors

Study Groups

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NBO (Normobaric Oxygen)

Oxygen, inhaled at 30-45L/min via a facemask for 8 hours

Group Type ACTIVE_COMPARATOR

NBO (Normobaric Oxygen)

Intervention Type DRUG

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

Intervention Type DRUG

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.

Room Air

Room Air, inhaled at 30-45L/min via a facemask for 8 hours

Group Type PLACEBO_COMPARATOR

NBO (Normobaric Oxygen)

Intervention Type DRUG

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

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

Massachusetts General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Aneesh B. Singhal, MD

Associate Professor of Neurology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Aneesh B Singhal, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General and Brigham & Women's Hospitals

Locations

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Massachusetts General Hospital, ACC-729C

Boston, Massachusetts, United States

Site Status

Brigham and Women's Hospital, 75 Francis Street

Boston, Massachusetts, United States

Site Status

Countries

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United States

References

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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. doi: 10.1161/01.STR.0000158914.66827.2e. Epub 2005 Mar 10.

Reference Type BACKGROUND
PMID: 15761201 (View on PubMed)

Kim HY, Singhal AB, Lo EH. Normobaric hyperoxia extends the reperfusion window in focal cerebral ischemia. Ann Neurol. 2005 Apr;57(4):571-5. doi: 10.1002/ana.20430.

Reference Type BACKGROUND
PMID: 15786465 (View on PubMed)

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. doi: 10.1212/wnl.58.6.945.

Reference Type BACKGROUND
PMID: 11914413 (View on PubMed)

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. doi: 10.1161/STROKEAHA.107.487280. Epub 2007 Aug 30.

Reference Type BACKGROUND
PMID: 17761914 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18706016 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19604385 (View on PubMed)

Regenhardt RW, Gonzalez RG, He J, Lev MH, Singhal AB. Symmetric CTA Collaterals Identify Patients with Slow-progressing Stroke Likely to Benefit from Late Thrombectomy. Radiology. 2022 Feb;302(2):400-407. doi: 10.1148/radiol.2021210455. Epub 2021 Nov 2.

Reference Type DERIVED
PMID: 34726532 (View on PubMed)

Related Links

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http://www.spotrias.com

Specialized Program of Translational Research in Acute Stroke website

Other Identifiers

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P50NS051343

Identifier Type: NIH

Identifier Source: secondary_id

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R01NS051412

Identifier Type: NIH

Identifier Source: org_study_id

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