Intracerebral HaemorrhageCHALLENGE-ICHNCT06410274
Ischaemic Lesions in Acute Intracerebral Haemorrhage
An observational study of Intracerebral Haemorrhage, run by University of Leicester at 1 site in United Kingdom.
Trial summary
The aim of this observational study is to determine how and why inadequate brain blood flow occurs after bleeding in patients with intracerebral haemorrhage (ICH). Treatment for strokes caused by burst blood vessels involves reducing blood pressure (BP) to stop the bleeding. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Intracerebral Haemorrhage
- What is being tested?
- Transcranial Doppler ultrasonography (TCD)
- Type of treatment
- Medical device
- How many people
- 120 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Jun 2024to 31 Jan 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The participants will be recruited from the Leicester Royal Infirmary stroke wards.
Who may be able to join
- Clinical diagnosis of a haemorrhagic stroke on CT imaging 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).
- Male or female, aged 18 years or above.
Who cannot join
- MRI imaging is contraindicated or unlikely to tolerate scanning process due to clinical instability (GCS <8, unable to lie supine).
- Patients requiring anaesthesia.
- Male or Female, aged under 18 years.
- Clinical diagnosis of stroke greater than 48 hours from onset
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
University Hospitals of Leicester NHS Trust
Leicester, LE1 5WW
Jatinder S Minhas, SFHEA, +441162523299, jm591@leicester.ac.uk
Jatinder S Minhas, SFHEA
About this study
Official title: Ischaemic Lesions in Acute Intracerebral Haemorrhage: Pathophysiological Investigation Using Novel Multimodal Cerebral and Systemic Haemodynamic Assessments
The aim of this observational study is to determine how and why inadequate brain blood flow occurs after bleeding in patients with intracerebral haemorrhage (ICH). Treatment for strokes caused by burst blood vessels involves reducing blood pressure (BP) to stop the bleeding. However, this reduction in BP may affect blood flow, causing blockages in blood vessels within the brain. Fast breathing also affects brain blood flow. Therefore, participants will be asked to undergo a simple brain blood flow assessment using transcranial Doppler (TCD) within 48 hours upon admission to hospital. Patients will then have a follow-up TCD assessment at 4-7 days post-ICH onset, in addition to an MRI scan at >7 days. This research will help to confirm if blockages after bleeding are caused by reduced blood flow within the brain.
Read the detailed description
Stroke is the second-leading cause of death worldwide, with high mortality and morbidity rates. One stroke type, intracerebral haemorrhage (ICH), refers to spontaneous, non-traumatic bleeding, within the brain tissue and is the second most common cause of stroke. Although ICH can happen at any age, it is more common over the age of 70. The most common cause of ICH is hypertension, which can cause bursting of cerebral blood vessels, resulting in bleeding within the brain. National and international guidelines strongly advocate systolic blood pressure (BP) lowering in ICH as part of "bundled" care, reducing fluctuations in cerebral blood velocity (CBv). However, despite blood pressure (BP) lowering being deemed clinically safe, no reduction in death or disability at 90 days was demonstrated in two landmark large randomised controlled trials. Moreover, reductions in BP may affect CBv to the whole of the brain, inadvertently causing ischaemic stroke (blockage of the blood supply).
Previous literature has identified that mild-to-moderate ICH stroke severity benefits from early and stable BP lowering, but those with excessively systolic high BP (>220 mmHg) prior to lowering suffer significantly higher rates of neurological deterioration. In order to understand the relationship between BP changes and potential clinical benefit in ICH, it needs to be determined if there is a global reduction in brain perfusion which is causing ischaemic lesions in the brain following ICH.
Prospective studies have shown impairments in dynamic cerebral autoregulation (dCA), cerebrovascular tone, and cerebrovascular resistance in acute ICH. Moreover, meta-analyses have demonstrated a previously unreported confounder to cerebral autoregulatory function: the presence of an acute reduction in spontaneous CO2 tension after ICH, potentially reflecting spontaneous hyperventilation (measured as partial pressure in arterial blood (pCO2) in patients in intensive care and on the ward). There is no current explanation for the presence of spontaneous hyperventilation post-ICH. However, it has been shown that across a range of end-tidal carbon dioxide (EtCO2) values, cerebral blood flow (CBF), dCA, and other core haemodynamic parameters (arterial BP and heart rate) have a dose-response relationship.
Fast breathing is also known to affect CBv. When EtCO2 is low, rapid acute cerebral vasoconstriction can occur - risking acute ischaemic injury. Therefore, in the presence of spontaneous hyperventilation or induced hyperventilation, reductions in brain perfusion through vasoconstriction could risk new or worsened ischaemic insults, particularly in the presence of BP lowering. Whilst the presence of cerebral small vessel disease plays a role in incidence of diffusion-weighted imaging (DWI) lesions after ICH, there have been no mechanistic association studies to date linking key confounding factors: BP lowering, EtCO2 change, dCA, and ischaemic lesions.
The investigators aim to perform transcranial Doppler (TCD) to measure CBv in patients with ICH within 48 hours of admission to hospital. These patients would then have a follow-up TCD assessment at 4-7 days post-ICH onset, in addition to a magnetic resonance imaging (MRI) scan (>7 days). Data would be collected and analysed to determine the relationship between cerebral haemodynamics and ischaemic lesions on MRI, post-acute ICH.
- Conditions
- Intracerebral Haemorrhage
- Being tested
- Transcranial Doppler ultrasonography (TCD)
- Keywords
- Stroke, Cerebral Autoregulation, Cerebral Blood Flow, Transcranial Doppler, Magnetic Resonance Imaging
- Medical subject headings
- Cerebral Hemorrhage, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Doppler ultrasonography (TCD)Device
TCD will be used to measure cerebral blood velocity (CBv) in the middle and posterior cerebral arteries (MCA and PCA). Following confirmation of a suitable TCD window, participants will undergo a ten-minute rest period in the supine or semi-supine position. Continuous measurements of CBv, blood pressure (BP), heart rate, and end-tidal carbon dioxide will be recorded. Baseline BP will be measured using an automated BP device prior to each recording to allow calibration of the files offline for analysis. This will occur at the first visit and at follow-up, 4-7 days post-onset of intracerebral haemorrhage.
| Study group | Role | What they receive |
|---|---|---|
| Intracerebral Haemorrhage Patients | Patients with a clinical diagnosis of haemorrhagic stroke on CT imaging 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). This is a non-intervention study so no intervention will be given. However, the investigators will observe changes in cerebral haemodynamics of this group within 48 hours of stroke onset and within 3-7 days post-onset. Receives: Device: Transcranial Doppler ultrasonography (TCD) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cerebral blood velocity measurements within 48 hours of admission to hospital and 4-7 days after onset in intracerebral haemorrhage patients.
Absolute values (cm/s) in cerebral blood velocity measurements in intracerebral haemorrhage patients.
Measured: From enrolment to the end of the follow-up (7 days).
Cerebral blood velocity measurements within 48 hours of admission to hospital and 4-7 days after onset in intracerebral haemorrhage patients.
Percentage change (%) in cerebral blood velocity measurements in intracerebral haemorrhage patients.
Measured: From enrolment to the end of the follow-up (7 days).
End-tidal carbon dioxide measurements within 48 hours of admission to hospital and 4-7 days after onset in intracerebral haemorrhage patients.
Absolute values (mmHg) in end-tidal carbon dioxide measurements in intracerebral haemorrhage patients.
Measured: From enrolment to the end of the follow-up (7 days).
End-tidal carbon dioxide measurements within 48 hours of admission to hospital and 4-7 days after onset in intracerebral haemorrhage patients.
Percentage change (%) in end-tidal carbon dioxide measurements in intracerebral haemorrhage patients.
Measured: From enrolment to the end of the follow-up (7 days).
Secondary outcomes (2)
Arterial spin labelling magnetic resonance imaging measurements >7 days post-intracerebral haemorrhage onset.
Absolute values (mL/g/min) in arterial spin labelling magnetic resonance imaging measurements of cerebral blood velocity in response to a respiratory challenge.
Measured: From enrolment to the magnetic resonance imaging scan (<7 days post-intracerebral haemorrhage onset).
Arterial spin labelling magnetic resonance imaging measurements >7 days post-intracerebral haemorrhage onset.
Percentage change (%) in arterial spin labelling magnetic resonance imaging measurements of cerebral blood velocity in response to a respiratory challenge (mL/g/min).
Measured: From enrolment to the magnetic resonance imaging scan (<7 days post-intracerebral haemorrhage onset).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2024
- Study start1 Jun 2024
- Primary completion31 Jan 2029 (estimated)
- Study completion31 Jan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intracerebral HaemorrhageStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Leicester
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospitals, Leicester
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06410274
- Sponsor's protocol ID
- 0966
- Acronym
- CHALLENGE-ICH
- Status last verified
- Apr 2024
- First submitted
- 7 May 2024
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual patient data will not be shared, however once analysed and combined (statistically through mean averages etc), the results will be compiled into a report and submitted to a relevant journal, allowing researchers to view them.
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ischaemic Lesions in Acute Intracerebral Haemorrhage: Pathophysiological Investigation Using Novel Multimodal Cerebral and Systemic Haemodynamic Assessments
- ClinicalTrials.gov ID
- NCT06410274
- Acronym / sponsor ID
- CHALLENGE-ICH / 0966
- Conditions
- Intracerebral Haemorrhage
- Keywords
- Stroke, Cerebral Autoregulation, Cerebral Blood Flow, Transcranial Doppler, Magnetic Resonance Imaging
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- University of LeicesterUniversity, hospital or other
- Collaborators
- University Hospitals, Leicester
- Study start
- 1 Jun 2024 (actual)
- Primary completion
- 31 Jan 2029 (estimated)
- Study completion
- 31 Jan 2029 (estimated)
- First posted
- 13 May 2024 (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.
The aim of this observational study is to determine how and why inadequate brain blood flow occurs after bleeding in patients with intracerebral haemorrhage (ICH). Treatment for strokes caused by burst blood vessels involves reducing blood pressure (BP) to stop the bleeding. However, this reduction in BP may affect blood flow, causing blockages in blood vessels within the brain. Fast breathing also affects brain blood flow. Therefore, participants will be asked to undergo a simple brain blood flow assessment using transcranial Doppler (TCD) within 48 hours upon admission to hospital. Patients will then have a follow-up TCD assessment at 4-7 days post-ICH onset, in addition to an MRI scan at >7 days. This research will help to confirm if blockages after bleeding are caused by reduced blood flow within the brain.
Detailed description
Stroke is the second-leading cause of death worldwide, with high mortality and morbidity rates. One stroke type, intracerebral haemorrhage (ICH), refers to spontaneous, non-traumatic bleeding, within the brain tissue and is the second most common cause of stroke. Although ICH can happen at any age, it is more common over the age of 70. The most common cause of ICH is hypertension, which can cause bursting of cerebral blood vessels, resulting in bleeding within the brain. National and international guidelines strongly advocate systolic blood pressure (BP) lowering in ICH as part of "bundled" care, reducing fluctuations in cerebral blood velocity (CBv). However, despite blood pressure (BP) lowering being deemed clinically safe, no reduction in death or disability at 90 days was demonstrated in two landmark large randomised controlled trials. Moreover, reductions in BP may affect CBv to the whole of the brain, inadvertently causing ischaemic stroke (blockage of the blood supply).
Previous literature has identified that mild-to-moderate ICH stroke severity benefits from early and stable BP lowering, but those with excessively systolic high BP (>220 mmHg) prior to lowering suffer significantly higher rates of neurological deterioration. In order to understand the relationship between BP changes and potential clinical benefit in ICH, it needs to be determined if there is a global reduction in brain perfusion which is causing ischaemic lesions in the brain following ICH.
Prospective studies have shown impairments in dynamic cerebral autoregulation (dCA), cerebrovascular tone, and cerebrovascular resistance in acute ICH. Moreover, meta-analyses have demonstrated a previously unreported confounder to cerebral autoregulatory function: the presence of an acute reduction in spontaneous CO2 tension after ICH, potentially reflecting spontaneous hyperventilation (measured as partial pressure in arterial blood (pCO2) in patients in intensive care and on the ward). There is no current explanation for the presence of spontaneous hyperventilation post-ICH. However, it has been shown that across a range of end-tidal carbon dioxide (EtCO2) values, cerebral blood flow (CBF), dCA, and other core haemodynamic parameters (arterial BP and heart rate) have a dose-response relationship.
Fast breathing is also known to affect CBv. When EtCO2 is low, rapid acute cerebral vasoconstriction can occur - risking acute ischaemic injury. Therefore, in the presence of spontaneous hyperventilation or induced hyperventilation, reductions in brain perfusion through vasoconstriction could risk new or worsened ischaemic insults, particularly in the presence of BP lowering. Whilst the presence of cerebral small vessel disease plays a role in incidence of diffusion-weighted imaging (DWI) lesions after ICH, there have been no mechanistic association studies to date linking key confounding factors: BP lowering, EtCO2 change, dCA, and ischaemic lesions.
The investigators aim to perform transcranial Doppler (TCD) to measure CBv in patients with ICH within 48 hours of admission to hospital. These patients would then have a follow-up TCD assessment at 4-7 days post-ICH onset, in addition to a magnetic resonance imaging (MRI) scan (>7 days). Data would be collected and analysed to determine the relationship between cerebral haemodynamics and ischaemic lesions on MRI, post-acute ICH.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intracerebral Haemorrhage Patients | – | Device: Transcranial Doppler ultrasonography (TCD)Patients with a clinical diagnosis of haemorrhagic stroke on CT imaging 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). This is a non-intervention study so no intervention will be given. However, the investigators will observe changes in cerebral haemodynamics of this group within 48 hours of stroke onset and within 3-7 days post-onset. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The participants will be recruited from the Leicester Royal Infirmary stroke wards.
Key inclusion criteria (2 listed)
- Clinical diagnosis of a haemorrhagic stroke on CT imaging 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).
- Male or female, aged 18 years or above.
Key exclusion criteria (4 listed)
- MRI imaging is contraindicated or unlikely to tolerate scanning process due to clinical instability (GCS <8, unable to lie supine).
- Patients requiring anaesthesia.
- Male or Female, aged under 18 years.
- 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 |
|---|---|---|
| Transcranial Doppler ultrasonography (TCD)TCD will be used to measure cerebral blood velocity (CBv) in the middle and posterior cerebral arteries (MCA and PCA). Following confirmation of a suitable TCD window, participants will undergo a ten-minute rest period in the supine or semi-supine position. Continuous measurements of CBv, blood pressure (BP), heart rate, and end-tidal carbon dioxide will be recorded. Baseline BP will be measured using an automated BP device prior to each recording to allow calibration of the files offline for analysis. This will occur at the first visit and at follow-up, 4-7 days post-onset of intracerebral haemorrhage. | Device | Intracerebral Haemorrhage Patients |
Primary outcome
Cerebral blood velocity measurements within 48 hours of admission to hospital and 4-7 days after onset in intracerebral haemorrhage patients.
Time frame: From enrolment to the end of the follow-up (7 days).
Absolute values (cm/s) in cerebral blood velocity measurements in intracerebral haemorrhage patients.
Cerebral blood velocity measurements within 48 hours of admission to hospital and 4-7 days after onset in intracerebral haemorrhage patients.
Time frame: From enrolment to the end of the follow-up (7 days).
Percentage change (%) in cerebral blood velocity measurements in intracerebral haemorrhage patients.
End-tidal carbon dioxide measurements within 48 hours of admission to hospital and 4-7 days after onset in intracerebral haemorrhage patients.
Time frame: From enrolment to the end of the follow-up (7 days).
Absolute values (mmHg) in end-tidal carbon dioxide measurements in intracerebral haemorrhage patients.
End-tidal carbon dioxide measurements within 48 hours of admission to hospital and 4-7 days after onset in intracerebral haemorrhage patients.
Time frame: From enrolment to the end of the follow-up (7 days).
Percentage change (%) in end-tidal carbon dioxide measurements in intracerebral haemorrhage patients.
2 secondary outcomes
Arterial spin labelling magnetic resonance imaging measurements >7 days post-intracerebral haemorrhage onset.
Time frame: From enrolment to the magnetic resonance imaging scan (<7 days post-intracerebral haemorrhage onset).
Arterial spin labelling magnetic resonance imaging measurements >7 days post-intracerebral haemorrhage onset.
Time frame: From enrolment to the magnetic resonance imaging scan (<7 days post-intracerebral haemorrhage onset).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Individual participant dataSharing planned: No. Individual patient data will not be shared, however once analysed and combined (statistically through mean averages etc), the results will be compiled into a report and submitted to a relevant journal, allowing researchers to view them.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Intracerebral Haemorrhage, 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 2 inclusion and 4 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: looking for participants now, as of the sponsor's last update on 19 Sep 2024. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jatinder Minhas, SFHEA (+44 116 252 3299, jm591@leicester.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cerebral blood velocity measurements within 48 hours of admission to hospital and 4-7 days after onset in intracerebral haemorrhage patients. (time frame: From enrolment to the end of the follow-up (7 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?
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 19 Sep 2024.