Ischaemic Lesions in Acute Intracerebral Haemorrhage

NCT ID: NCT06410274

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 120 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-06-01
• Study Completion Date: 2029-01-31

Brief 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. 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.

Conditions

Intracerebral Haemorrhage

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

Transcranial Doppler ultrasonography (TCD)

Intervention Type: 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.

Interventions

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.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospitals, Leicester

OTHER

Sponsor Role: collaborator

University of Leicester

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University Hospitals of Leicester NHS Trust

Leicester, , United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Jatinder Minhas, SFHEA

Role: CONTACT

jm591@leicester.ac.uk

+44 116 252 3299

Facility Contacts

Jatinder S Minhas, SFHEA

Role: primary

jm591@leicester.ac.uk

+441162523299

Other Identifiers

0966

Identifier Type: -

Identifier Source: org_study_id