Intensive Blood Pressure Control in Ischaemic Stroke Patients With Severe Cerebral Small Vessel Disease

Sponsor

The University of Hong Kong (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05690997

Collaborator

(none)

104

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Objectives: Cerebral small vessel disease (SVD) is a common disease in patients with ischemic stroke and the most common cause of vascular dementia. Blood pressure (BP)-lowering is generally considered neuroprotective. Nevertheless, in patients with severe SVD burden, the optimal BP target is uncertain.

Hypothesis: BP-lowering to a systolic BP of 120-129mmHg in ischemic stroke patients with severe SVD is not associated with impaired cerebral perfusion, nor does it associate with worsening of structural connectivity and cognitive function.

Design and subjects: One-year trial where patients aged ≥50 with a history of ischaemic stroke and severe cerebral SVD will be randomised (1:1) to a systolic BP target of 120-129mmHg versus 130-140mmHg.

Study instruments: At baseline and one-year, all subjects will receive a brain magnetic resonance imaging (MRI) to evaluate their cerebral blood flow (CBF) and white matter integrity. They will also receive neuropsychological batteries to evaluate cognitive functioning. In addition, subjects will receive home BP monitoring with periodic medication changes prescribed by medical doctor to ensure the target BP is achieved.

Main outcome measures: Primary end-point is the change in CBF. Secondary end-points include changes in structural connectivity and cognitive performance.

Condition or Disease	Intervention/Treatment	Phase
Small Vessel Cerebrovascular Disease Stroke	Other: Intensive treatment Other: Standard treatment	N/A

Detailed Description

Cerebral small vessel disease (SVD) is a common disease in patients with ischemic stroke and the most common cause of vascular dementia. The global burden of cerebral SVD is high and strategies to better prevent and manage cerebral SVD is urgently needed. Whilst blood pressure (BP) lowering is considered neuroprotective in patients with cerebral SVD, the optimal BP target in ischaemic stroke patients with severe SVD remains uncertain. Therefore, this randomised clinical trial aims to investigate whether two selected systolic blood pressure targets [systolic BP (SBP) 120-129mmHg versus 130-140mmHg] have different effects on cerebral blood flow and white matter integrity (structural connectivity) detected by magnetic resonance imaging (MRI) of the brain, as well as on cognition, over a one-year intervention period.

Chinese patients aged ≥50 with a prior history of TIA/ischaemic stroke fitting the inclusion and exclusion criteria will be recruited. At baseline, recruited subjects will undergo clinical and cognitive assessments. Blood pressure will be measured at clinic with an automated BP measurement system. A baseline non-contrast MRI of the brain will be arranged. The non-contrast MRI and cognitive assessments will be repeated at approximately 1 year after recruitment into the study.

To ensure consistency, our trial's antihypertensive strategy and titration shall align with those recommended by international guidelines. Blood tests for renal function will be arranged after modifying the prescription of specific anti-hypertensive agents (e.g. ACEis, ARBs, thiazide diuretics and spironolactone).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

104 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Intensive treatment group: if the mean home SBP preceding clinic follow-up is >130mmHg, BP lowering treatment will be stepped up, and if the mean SBP preceding clinic follow-up is <120mmHg, BP lowering treatment will be stepped down, until the target SBP of 120-129mmHg is achieved, or symptoms of hypotension prevent treatment to be further intensified. Standard treatment group: if the mean home SBP preceding clinic follow-up is >140mmHg, BP lowering treatment will be stepped up, and if the mean SBP preceding clinic follow-up is <130mmHg, BP lowering will be stepped down, until the target SBP 130-140mmg is achieved or symptoms of hypotension prevent treatment being intensified.Intensive treatment group:if the mean home SBP preceding clinic follow-up is >130mmHg, BP lowering treatment will be stepped up, and if the mean SBP preceding clinic follow-up is <120mmHg, BP lowering treatment will be stepped down, until the target SBP of 120-129mmHg is achieved, or symptoms of hypotension prevent treatment to be further intensified.Standard treatment group:if the mean home SBP preceding clinic follow-up is >140mmHg, BP lowering treatment will be stepped up, and if the mean SBP preceding clinic follow-up is <130mmHg, BP lowering will be stepped down, until the target SBP 130-140mmg is achieved or symptoms of hypotension prevent treatment being intensified.

Masking:

Single (Outcomes Assessor)

Masking Description:

To avoid bias in outcome assessment, evaluation of the primary and secondary outcome measures will be performed by a group who is independent from the clinical investigators and who will be blinded from all clinical, cognitive and radiological assessments.

Primary Purpose:

Treatment

Official Title:

Effect of Intensive Blood Pressure Control on Cerebral Blood Flow and Cognition in Ischaemic Stroke Patients With Severe Cerebral Small Vessel Disease

Anticipated Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Jun 1, 2024

Anticipated Study Completion Date :

Jun 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Other: Intensive Treatment Group SBP target 120-129 mmHg	Other: Intensive treatment If the mean home SBP preceding clinic follow-up is >130mmHg, BP lowering treatment will be stepped up, and if the mean SBP preceding clinic follow-up is <120mmHg, BP lowering treatment will be stepped down, until the target SBP of 120-129mmHg is achieved, or symptoms of hypotension prevent treatment to be further intensified.
Other: Standard Treatment Group SBP target 130-140 mmHg	Other: Standard treatment If the mean home SBP preceding clinic follow-up is >140mmHg, BP lowering treatment will be stepped up, and if the mean SBP preceding clinic follow-up is <130mmHg, BP lowering will be stepped down, until the target SBP 130-140mmg is achieved or symptoms of hypotension prevent treatment being intensified.

Arm

Intervention/Treatment

Other: Intensive Treatment Group

SBP target 120-129 mmHg

Other: Intensive treatment

If the mean home SBP preceding clinic follow-up is >130mmHg, BP lowering treatment will be stepped up, and if the mean SBP preceding clinic follow-up is <120mmHg, BP lowering treatment will be stepped down, until the target SBP of 120-129mmHg is achieved, or symptoms of hypotension prevent treatment to be further intensified.

Other: Standard Treatment Group

SBP target 130-140 mmHg

Other: Standard treatment

If the mean home SBP preceding clinic follow-up is >140mmHg, BP lowering treatment will be stepped up, and if the mean SBP preceding clinic follow-up is <130mmHg, BP lowering will be stepped down, until the target SBP 130-140mmg is achieved or symptoms of hypotension prevent treatment being intensified.

Outcome Measures

Primary Outcome Measures

Cerebral Blood Flow [From Baseline to approximate 1 year after recruitment]
Change in whole-brain CBF as measured using MRI ASL at end of study (1 year) compared to baseline.

Secondary Outcome Measures

Grey Matter - Cerebral Blood Flow [From Baseline to approximate 1 year after recruitment]
Change in Grey Matter CBF as measured using MRI ASL at end of study (1 year) compared to baseline.
White Matter - Cerebral Blood Flow [From Baseline to approximate 1 year after recruitment]
Change in white matter CBF as measured using MRI ASL at end of study (1 year) compared to baseline.
Structural Connectivity [From Baseline to approximate 1 year after recruitment]
Change in structural connectivity CBF as measured using MRI DTI at end of study (1 year) compared to baseline.
Cognitive Function - MoCA [From Baseline to approximate 1 year after recruitment]
Change in MoCA Score at end of study (1 year)
Cognitive Function - Stroop colour-word test [From Baseline to approximate 1 year after recruitment]
Change in Stroop colour-word test Score at end of study (1 year)
Cognitive Function - Digit Symbol Coding test [From Baseline to approximate 1 year after recruitment]
Change in Digital Symbol Coding test Score at end of study (1 year)

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Aged ≥50
Chinese ethnicity
History of TIA/ischaemic stroke
Underlying severe cerebral SVD as evidenced by brain MRI with total SVD score ≥3
Underlying hypertension (defined as either SBP >140mmHg and taking no more than two anti-hypertensive agents, or SBP between 130-140mmHg and on at least one and not more than three anti-hypertensive agents)
Able to provide written informed consent
Able to perform study cognitive assessments
Modified Rankin Scale (mRS) ≤3
Expected life expectancy >2 years

Exclusion Criteria:

Unable to, or unwilling to consent
TIA/ischaemic stroke within three months (to avoid confounding effects of recovery on cognition from recent stroke)
Brain MR angiogram showing significant symptomatic or asymptomatic carotid, vertebral or intracranial large artery stenosis ≥50% as measured using the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria
Cortical infarction >2cm in diameter
Paroxysmal or permanent atrial fibrillation
Known single gene disorder causing cerebral SVD, e.g. cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)
Symptomatic postural hypotension
Moderate- and severe-stage dementia with Montreal Cognitive Assessment (MOCA)-HK score <10
Moderate and severe depressive symptoms with Patient Health Questionnaire-9 score ≥10
Known secondary hypertension, e.g. hypertension is due to established obstructive sleep apnoea, renal parenchymal disease, renal artery stenosis, primary aldosteronism etc.
Unable to complete cognitive assessments
mRS >3
Life expectancy of less than 2 years