Stroke, AcuteBREATHE-ICHNCT03324321
Feasibility of Improving Cerebral Autoregulation in Acute Intracerebral Haemorrhage
A study testing Hypocapnia via Hyperventilation Protocol in people with Stroke, Acute and Hemorrhage, run by University of Leicester at 1 site in United Kingdom.
Trial summary
In the UK, 23,000 (15%) of the 150,000 people who suffer a stroke each year have bleeding in the brain, also referred to as acute intracerebral haemorrhage (ICH). An Autoregulation Index (ARI) can be assigned between 0 and 9 (0 being poor and 9 being the most efficient CA observed) to gauge how good the control over… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stroke, Acute, Hemorrhage, Cerebral Brain Hemorrhage
- What is being tested?
- Hypocapnia via Hyperventilation Protocol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 8 Oct 2017to 15 Jul 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- Clinical diagnosis of a haemorrhagic stroke within 48 hours of onset (for patients waking with a stroke, time of onset will be taken to be the time when the patient was last asymptomatic)
- Able and willing to give informed consent
- Male or female, aged 18 years or above
- Able (in the Investigator's opinion) and willing to comply with all study requirements
- Willing to allow his or her General Practitioner (GP) to be notified of participation in the study
Who cannot join
- Male or Female, aged under 18 years
- Significant previous airways disease (formal diagnosis of moderate or severe airways disease and having treatment for this respiratory condition - via inhalers or specialist input)
- Unable (in the Investigator's opinion) or unwilling to comply with any study requirements
- Female participants who are pregnant, lactating or planning pregnancy during the course of the study
- Clinical diagnosis of stroke greater than 48 hours from onset
- Having had a resolved transient ischaemic attack (TIA) (i.e. neurological symptoms completely resolved upon hospital presentation)
- Co-morbidity with anticipated life expectancy less than 3 months
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University Hospitals of Leicester NHS Trust
Leicester
About this study
Official title: Feasibility of Improving Cerebral Autoregulation in Acute Intracerebral Haemorrhage (BREATHE-ICH) Study
In the UK, 23,000 (15%) of the 150,000 people who suffer a stroke each year have bleeding in the brain, also referred to as acute intracerebral haemorrhage (ICH). An Autoregulation Index (ARI) can be assigned between 0 and 9 (0 being poor and 9 being the most efficient CA observed) to gauge how good the control over blood flow is at a given time. Dynamic CA (dCA) is a measure of the response of cerebral blood flow (CBF) to rapid changes in blood pressure (BP), and several key studies have shown impaired dCA post-acute ICH. The most recent study demonstrated that dCA impairment lasts up to 12 days. This is particularly important to understand, since our preliminary work has recently shown that changes in carbon dioxide using simple breathing exercises can improve Autoregulation.
Unfortunately, there are limited non-pharmacological management options and significant opportunities to improve patient outcome in ICH. The proposed study addresses this area, by investigating whether a simple breathing exercise in survivors of ICH is safe, feasible and effective in reducing brain injury by improving cerebral autoregulation.
- Conditions
- Stroke, Acute, Hemorrhage, Cerebral Brain Hemorrhage, Blood Pressure
- Being tested
- Hypocapnia via Hyperventilation Protocol
- Keywords
- Cerebral Haemodynamics, Carbon Dioxide, Cerebral Autoregulation
- Medical subject headings
- Stroke, Hemorrhage, Cerebral Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hypocapnia via Hyperventilation ProtocolOther
90 seconds of hyperventilation using a metronome to lower levels of -5mmHg and -10mmHg below baseline EtCO2
| Study group | Role | What they receive |
|---|---|---|
| Hyperventilation Protocol | Experimental | This will involve sustained periods of 90-seconds of hyperventilation at two levels (-5mmHg and -10mmHg below baseline EtCO2) to a maximum lower level threshold of EtCO2 24mmHg/CBFV 33cm/s regulated using a metronome. Two-minute washout periods of normal respiration will be allowed between successive measurements. Each incremental reduction in pCO2 will be repeated on two occasions during the same session. Further assessments will be conducted 10-14 days following baseline assessments. Receives: Other: Hypocapnia via Hyperventilation Protocol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Post Stroke Morbidity and Mortality
Determined using Modified Rankin Scale 0 - No symptoms
- - No significant disability, despite symptoms; able to perform all usual duties and activities
- - Slight disability; unable to perform all previous activities but able to look after own affairs without assistance
- - Moderate disability; requires some help, but able to walk without assistance
- - Moderate severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance
- - Severe disability; bedridden, incontinent, and requires constant care 6- Death
Measured: 14 days
The percentage of recruited subjects able to comply with the full measurement protocol
Measured: 14 days
The percentage of measurements rejected because of aspects related to data quality during the analysis protocol, with recorded reasons
Measured: 14 days
The percentage of recruited subjects in whom values for the following cerebral haemodynamic parameters can be derived
- % change in CBFv at baseline and in response to a hyperventilation manoeuvre in the acute (<48 hours) and sub-acute (10 to 14 days) periods
- Autoregulation index
- % change in CBFv at baseline and in response to a hyperventilation manoeuvre in the acute (<48 hours) and sub-acute (10 to 14 days) periods
- Autoregulation index
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2017
- Study start8 Oct 2017
- Primary completion15 Jul 2018
- Study completion15 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Stroke, AcuteStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single-centre, prospective, before and after study
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Leicester
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Thompson G Robinson, MD, FRCP, Principal investigator, University of Leicester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03324321
- Sponsor's protocol ID
- 0624
- Acronym
- BREATHE-ICH
- Status last verified
- Oct 2018
- First submitted
- 9 Oct 2017
- Last updated
- 31 Oct 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Tiecks FP, Lam AM, Aaslid R, Newell DW. Comparison of static and dynamic cerebral autoregulation measurements. Stroke. 1995 Jun;26(6):1014-9. doi: 10.1161/01.str.26.6.1014.
PubMed 7762016Ma H, Guo ZN, Liu J, Xing Y, Zhao R, Yang Y. Temporal Course of Dynamic Cerebral Autoregulation in Patients With Intracerebral Hemorrhage. Stroke. 2016 Mar;47(3):674-81. doi: 10.1161/STROKEAHA.115.011453. Epub 2016 Feb 4.
PubMed 26846864Minhas JS, Panerai RB, Swienton D, Robinson TG. Feasibility of improving cerebral autoregulation in acute intracerebral hemorrhage (BREATHE-ICH) study: Results from an experimental interventional study. Int J Stroke. 2020 Aug;15(6):627-637. doi: 10.1177/1747493019873690. Epub 2019 Sep 9.
PubMed 31500552Minhas JS, Panerai RB, Robinson TG. Feasibility of Improving Cerebral Autoregulation in Acute Intracerebral Haemorrhage (BREATHE-ICH) study: a protocol for an experimental interventional study. BMJ Open. 2018 Mar 27;8(3):e020758. doi: 10.1136/bmjopen-2017-020758.
PubMed 29593024
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Feasibility of Improving Cerebral Autoregulation in Acute Intracerebral Haemorrhage (BREATHE-ICH) Study
- ClinicalTrials.gov ID
- NCT03324321
- Acronym / sponsor ID
- BREATHE-ICH / 0624
- Conditions
- Stroke, Acute, Hemorrhage, Cerebral Brain Hemorrhage, Blood Pressure
- Keywords
- Cerebral Haemodynamics, Carbon Dioxide, Cerebral Autoregulation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University of LeicesterUniversity, hospital or other
- Study start
- 8 Oct 2017 (actual)
- Primary completion
- 15 Jul 2018 (actual)
- Study completion
- 15 Jul 2018 (actual)
- First posted
- 27 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In the UK, 23,000 (15%) of the 150,000 people who suffer a stroke each year have bleeding in the brain, also referred to as acute intracerebral haemorrhage (ICH). An Autoregulation Index (ARI) can be assigned between 0 and 9 (0 being poor and 9 being the most efficient CA observed) to gauge how good the control over blood flow is at a given time. Dynamic CA (dCA) is a measure of the response of cerebral blood flow (CBF) to rapid changes in blood pressure (BP), and several key studies have shown impaired dCA post-acute ICH. The most recent study demonstrated that dCA impairment lasts up to 12 days. This is particularly important to understand, since our preliminary work has recently shown that changes in carbon dioxide using simple breathing exercises can improve Autoregulation.
Unfortunately, there are limited non-pharmacological management options and significant opportunities to improve patient outcome in ICH. The proposed study addresses this area, by investigating whether a simple breathing exercise in survivors of ICH is safe, feasible and effective in reducing brain injury by improving cerebral autoregulation.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single-centre, prospective, before and after study
| Arm | Type | Receives |
|---|---|---|
| Hyperventilation Protocol | Experimental | Other: Hypocapnia via Hyperventilation ProtocolThis will involve sustained periods of 90-seconds of hyperventilation at two levels (-5mmHg and -10mmHg below baseline EtCO2) to a maximum lower level threshold of EtCO2 24mmHg/CBFV 33cm/s regulated using a metronome. Two-minute washout periods of normal respiration will be allowed between successive measurements. Each incremental reduction in pCO2 will be repeated on two occasions during the same session. Further assessments will be conducted 10-14 days following baseline assessments. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Clinical diagnosis of a haemorrhagic stroke within 48 hours of onset (for patients waking with a stroke, time of onset will be taken to be the time when the patient was last asymptomatic)
- Able and willing to give informed consent
- Male or female, aged 18 years or above
- Able (in the Investigator's opinion) and willing to comply with all study requirements
- Willing to allow his or her General Practitioner (GP) to be notified of participation in the study
Key exclusion criteria (7 listed)
- Male or Female, aged under 18 years
- Significant previous airways disease (formal diagnosis of moderate or severe airways disease and having treatment for this respiratory condition - via inhalers or specialist input)
- Unable (in the Investigator's opinion) or unwilling to comply with any study requirements
- Female participants who are pregnant, lactating or planning pregnancy during the course of the study
- Clinical diagnosis of stroke greater than 48 hours from onset
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 |
|---|---|---|
| Hypocapnia via Hyperventilation Protocol90 seconds of hyperventilation using a metronome to lower levels of -5mmHg and -10mmHg below baseline EtCO2 | Other | Hyperventilation Protocol |
Primary outcome
Post Stroke Morbidity and Mortality
Time frame: 14 days
Determined using Modified Rankin Scale 0 - No symptoms 1. - No significant disability, despite symptoms; able to perform all usual duties and activities 2. - Slight disability; unable to perform all previous activities but able to look after own affairs without assistance 3. - Moderate disability; requires some help, but able to walk without assistance 4. - Moderate severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance 5. - Severe disability; bedridden, incontinent, and requires constant care 6- Death
The percentage of recruited subjects able to comply with the full measurement protocol
Time frame: 14 days
The percentage of measurements rejected because of aspects related to data quality during the analysis protocol, with recorded reasons
Time frame: 14 days
The percentage of recruited subjects in whom values for the following cerebral haemodynamic parameters can be derived
Time frame: 14 days
* % change in CBFv at baseline and in response to a hyperventilation manoeuvre in the acute (<48 hours) and sub-acute (10 to 14 days) periods * Autoregulation index * % change in CBFv at baseline and in response to a hyperventilation manoeuvre in the acute (<48 hours) and sub-acute (10 to 14 days) periods * Autoregulation index
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2018.
- Background: PubMed 7762016Tiecks FP, Lam AM, Aaslid R, Newell DW. Comparison of static and dynamic cerebral autoregulation measurements. Stroke. 1995 Jun;26(6):1014-9. doi: 10.1161/01.str.26.6.1014.
- Background: PubMed 26846864Ma H, Guo ZN, Liu J, Xing Y, Zhao R, Yang Y. Temporal Course of Dynamic Cerebral Autoregulation in Patients With Intracerebral Hemorrhage. Stroke. 2016 Mar;47(3):674-81. doi: 10.1161/STROKEAHA.115.011453. Epub 2016 Feb 4.
- Derived from this study: PubMed 31500552Minhas JS, Panerai RB, Swienton D, Robinson TG. Feasibility of improving cerebral autoregulation in acute intracerebral hemorrhage (BREATHE-ICH) study: Results from an experimental interventional study. Int J Stroke. 2020 Aug;15(6):627-637. doi: 10.1177/1747493019873690. Epub 2019 Sep 9.
- Derived from this study: PubMed 29593024Minhas JS, Panerai RB, Robinson TG. Feasibility of Improving Cerebral Autoregulation in Acute Intracerebral Haemorrhage (BREATHE-ICH) study: a protocol for an experimental interventional study. BMJ Open. 2018 Mar 27;8(3):e020758. doi: 10.1136/bmjopen-2017-020758.
- Individual participant dataSharing planned: No
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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.
Thompson G Robinson, MD, FRCP principal investigator
University of Leicester
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Hypocapnia via Hyperventilation Protocol in people with Stroke, Acute and Hemorrhage, run by University of Leicester at 1 site in United Kingdom.
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 5 inclusion and 7 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: finished, as of the sponsor's last update on 31 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Post Stroke Morbidity and Mortality (time frame: 14 days). The study lists 4 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 NCT03324321, which also lists 4 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 31 Oct 2018.