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Normobaric Oxygen Therapy in Acute Ischemic Stroke Trial

Primary Purpose

Ischemic Stroke

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

NBO (Normobaric Oxygen)

Room Air

About this trial

This is an interventional treatment trial for Ischemic Stroke focused on measuring ischemic stroke, normobaric oxygen therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Massachusetts General Hospital, ACC-729C
Brigham and Women's Hospital, 75 Francis Street

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

NBO (Normobaric Oxygen)

Room Air

Arm Description

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

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

Outcomes

Primary Outcome Measures

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).

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).

Secondary Outcome Measures

Full Information

NCT ID

NCT00414726

First Posted

December 21, 2006

Last Updated

October 18, 2017

Sponsor

Massachusetts General Hospital

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

1. Study Identification

Unique Protocol Identification Number

NCT00414726

Brief Title

Normobaric Oxygen Therapy in Acute Ischemic Stroke Trial

Official Title

Clinical Trial of Normobaric Oxygen Therapy in Acute Ischemic Stroke

Study Type

Interventional

2. Study Status

Record Verification Date

October 2017

Overall Recruitment Status

Terminated

Why Stopped

Imbalance in deaths favoring control arm; deaths not attributed to treatment by the blinded external medical monitor.

Study Start Date

January 2007 (undefined)

Primary Completion Date

June 2009 (Actual)

Study Completion Date

June 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Massachusetts General Hospital

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Ischemic Stroke

Keywords

ischemic stroke, normobaric oxygen therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderOutcomes Assessor

Allocation

Randomized

Enrollment

85 (Actual)

8. Arms, Groups, and Interventions

Arm Title

NBO (Normobaric Oxygen)

Arm Type

Active Comparator

Arm Description

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

Arm Title

Room Air

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

NBO (Normobaric Oxygen)

Intervention Description

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

Intervention Name(s)

Room Air

Intervention Description

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.

Primary Outcome Measure Information:

Title

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.

Description

The NIHSS score ranges from 0 (best score) to 42 (worst score).

Time Frame

24 hours

Title

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.

Description

The NIHSS score ranges from 0 (best score) to 42 (worst score).

Time Frame

4 hours after starting treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Aneesh B Singhal, MD

Organizational Affiliation

Massachusetts General and Brigham & Women's Hospitals

Official's Role

Principal Investigator

Facility Information:

Facility Name

Massachusetts General Hospital, ACC-729C

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

Brigham and Women's Hospital, 75 Francis Street

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

15761201

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

Results Reference

background

PubMed Identifier

15786465

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. doi: 10.1002/ana.20430.

Results Reference

background

PubMed Identifier

11914413

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. doi: 10.1212/wnl.58.6.945.

Results Reference

background

PubMed Identifier

17761914

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

Results Reference

background

PubMed Identifier

18706016

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.

Results Reference

background

PubMed Identifier

19604385

Citation

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.

Results Reference

background

PubMed Identifier

34726532

Citation

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.

Results Reference

derived

Links:

URL

http://www.spotrias.com

Description

Specialized Program of Translational Research in Acute Stroke website

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Normobaric Oxygen Therapy in Acute Ischemic Stroke Trial

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