Ischemic StrokePhase 2NCT00414726
Normobaric Oxygen Therapy in Acute Ischemic Stroke Trial
A Phase 2 study testing NBO (Normobaric Oxygen) and Room Air in people with Ischemic Stroke, run by Massachusetts General Hospital at 2 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ischemic Stroke
- What is being tested?
- NBO (Normobaric Oxygen) and Room Air
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 85 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2007to Jun 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts General Hospital, ACC-729C
Boston, Massachusetts, 02114
Brigham and Women's Hospital, 75 Francis Street
Boston, Massachusetts, 02115
About this study
Official title: Clinical Trial of Normobaric Oxygen Therapy in Acute Ischemic Stroke
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.
Read the 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.
- Conditions
- Ischemic Stroke
- Being tested
- NBO (Normobaric Oxygen), Room Air
- Keywords
- ischemic stroke, normobaric oxygen therapy
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NBO (Normobaric Oxygen)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 AirDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| NBO (Normobaric Oxygen) | Active comparator | Oxygen, inhaled at 30-45L/min via a facemask for 8 hours Receives: Drug: NBO (Normobaric Oxygen); Drug: Room Air |
| Room Air | Placebo comparator | Room Air, inhaled at 30-45L/min via a facemask for 8 hours Receives: Drug: NBO (Normobaric Oxygen); Drug: Room Air |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 24 hours
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).
Measured: 4 hours after starting treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2006 (estimated)
- Study startJan 2007
- Primary completionJun 2009
- Study completionJun 2009
Why it stopped: Imbalance in deaths favoring control arm; deaths not attributed to treatment by the blinded external medical monitor.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Ischemic StrokeStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Principal investigator, Aneesh B. Singhal, MD, Massachusetts General Hospital
- Investigators
- Aneesh B Singhal, MD, Principal investigator, Massachusetts General and Brigham & Women's Hospitals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00414726
- Sponsor's protocol ID
- R01NS051412
- Other IDs
- P50NS051343
- Status last verified
- Oct 2017
- First submitted
- 21 Dec 2006
- Last updated
- 20 Oct 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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. doi: 10.1161/01.STR.0000158914.66827.2e. Epub 2005 Mar 10.
PubMed 15761201Kim 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.
PubMed 15786465Singhal 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.
PubMed 11914413Singhal 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.
PubMed 17761914Singhal 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.
PubMed 18706016Fujiwara 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.
PubMed 19604385Regenhardt 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.
PubMed 34726532
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Trial of Normobaric Oxygen Therapy in Acute Ischemic Stroke
- ClinicalTrials.gov ID
- NCT00414726
- Acronym / sponsor ID
- R01NS051412
- Conditions
- Ischemic Stroke
- Keywords
- ischemic stroke, normobaric oxygen therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Imbalance in deaths favoring control arm; deaths not attributed to treatment by the blinded external medical monitor.
- Enrolment
- 85 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Jan 2007
- Primary completion
- Jun 2009 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 22 Dec 2006 (estimated)
- Results
- Posted 16 Sep 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NBO (Normobaric Oxygen) | Active comparator | Drug: NBO (Normobaric Oxygen), Drug: Room AirOxygen, inhaled at 30-45L/min via a facemask for 8 hours |
| Room Air | Placebo comparator | Drug: NBO (Normobaric Oxygen), Drug: Room AirRoom Air, inhaled at 30-45L/min via a facemask for 8 hours |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (17 listed)
- 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%.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | NBO (Normobaric Oxygen), Room Air |
| Room AirRoom 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. | Drug | NBO (Normobaric Oxygen), Room Air |
Primary outcome
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.
Time frame: 24 hours
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.
Time frame: 4 hours after starting treatment
The NIHSS score ranges from 0 (best score) to 42 (worst score).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15761201Singhal 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.
- Background: PubMed 15786465Kim 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.
- Background: PubMed 11914413Singhal 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.
- Background: PubMed 17761914Singhal 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.
- Background: PubMed 18706016Singhal 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.
- Background: PubMed 19604385Fujiwara 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.
- Derived from this study: PubMed 34726532Regenhardt 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.
- Specialized Program of Translational Research in Acute Stroke websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Aneesh B Singhal, MD principal investigator
Massachusetts General and Brigham & Women's Hospitals
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NBO (Normobaric Oxygen) and Room Air in people with Ischemic Stroke, run by Massachusetts General Hospital at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Sep 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 24 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00414726, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2017.