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

Stroke Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05690997
• Other study ID #: GL2021001
• Secondary ID: UW21-128
• Status: Recruiting
• Phase: N/A
• Start date: January 9, 2023
• Est. completion date: June 2025

Study information

• Verified date: February 2023
• Source: The University of Hong Kong
• Contact: Gary KK LAU
• Phone: 852-22554249
• Email: gkklau[@]hku.hk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 104
• Est. completion date: June 2025
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

1. Aged =50

2. Chinese ethnicity

3. History of TIA/ischaemic stroke

4. Underlying severe cerebral SVD as evidenced by brain MRI with total SVD score =3

5. 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)

6. Able to provide written informed consent

7. Able to perform study cognitive assessments

8. Modified Rankin Scale (mRS) =3

9. Expected life expectancy >2 years

Exclusion Criteria:

1. Unable to, or unwilling to consent

2. TIA/ischaemic stroke within three months (to avoid confounding effects of recovery on cognition from recent stroke)

3. 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

4. Cortical infarction >2cm in diameter

5. Paroxysmal or permanent atrial fibrillation

6. Known single gene disorder causing cerebral SVD, e.g. cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

7. Symptomatic postural hypotension

8. Moderate- and severe-stage dementia with Montreal Cognitive Assessment (MOCA)-HK score <10

9. Moderate and severe depressive symptoms with Patient Health Questionnaire-9 score =10

10. Known secondary hypertension, e.g. hypertension is due to established obstructive sleep apnoea, renal parenchymal disease, renal artery stenosis, primary aldosteronism etc.

11. Unable to complete cognitive assessments

12. mRS >3

13. Life expectancy of less than 2 years

Related Conditions & MeSH terms

• Cerebral Small Vessel Diseases
• Cerebrovascular Disorders
• Ischemic Stroke
• Small Vessel Cerebrovascular Disease
• Stroke

Intervention

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.
• 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.

Locations

Country	Name	City	State
Hong Kong	University of Hong Kong	Hong Kong

Sponsors (1)

Lead Sponsor	Collaborator
The University of Hong Kong

Country where clinical trial is conducted

Hong Kong, 

References & Publications (25)

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* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cerebral Blood Flow	Change in whole-brain CBF as measured using MRI ASL at end of study (1 year) compared to baseline.	From Baseline to approximate 1 year after recruitment
Secondary	Grey Matter - Cerebral Blood Flow	Change in Grey Matter CBF as measured using MRI ASL at end of study (1 year) compared to baseline.	From Baseline to approximate 1 year after recruitment
Secondary	White Matter - Cerebral Blood Flow	Change in white matter CBF as measured using MRI ASL at end of study (1 year) compared to baseline.	From Baseline to approximate 1 year after recruitment
Secondary	Structural Connectivity	Change in structural connectivity CBF as measured using MRI DTI at end of study (1 year) compared to baseline.	From Baseline to approximate 1 year after recruitment
Secondary	Cognitive Function - MoCA	Change in MoCA Score at end of study (1 year)	From Baseline to approximate 1 year after recruitment
Secondary	Cognitive Function - Stroop colour-word test	Change in Stroop colour-word test Score at end of study (1 year)	From Baseline to approximate 1 year after recruitment
Secondary	Cognitive Function - Digit Symbol Coding test	Change in Digital Symbol Coding test Score at end of study (1 year)	From Baseline to approximate 1 year after recruitment