Strategy for Adequate Blood Pressure Lowering in the Patients With Intracranial Atherosclerosis

Study Overview
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Brief Summary
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To develop adequate blood pressure (BP) lowering strategy after subacute ischemic stroke patients with symptomatic severe intracranial atherosclerosis. Primary hypothesis of this study is that aggressive BP control (lowering systolic BP between 110mmHg and 120mmHg) will not increase the ischemic lesion volumes in hemisphere compared to modest BP lowering (lowering systolic BP between 130mmHg and 140mmHg) in the patients with symptomatic severe intracranial atherosclerosis.

Detailed Description
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The benefits of BP lowering in the prevention of primary and secondary prevention of stroke is established well, although absolute target BP level is uncertain. Current guidelines defined the normal BP as <120/80mmHg and recommend individualized target BP level. Large well performed stroke prevention trials consistently showed that reduction of 10/5mmHg in patients with systolic BP below 140mmHg had clear benefits in the prevention of cardiovascular events. However, we have a dilemma about BP control in the patients with severe intracranial atherosclerosis. Aggressive BP control will be more effective in the prevention of overall cardiovascular events than modest BP control, but aggressive BP control will reduce cerebral perfusion in the territory of severe intracranial disease and may increase the risk of ischemic damage. The study will try to reveal aggressive BP control in the patients with symptomatic severe intracranial atherosclerosis is not increase ischemic lesion volume in hemisphere to compare modest BP control.

Official Title
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Multicenter Clinical Trial for Development of Guidelines of Adequate Blood Pressure Lowering in the Subacute Ischemic Stroke Patients Due to Intracranial Atherosclerosis

Conditions
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Brain Ischemia

Intervention / Treatment
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* Procedure: Aggressive BP lowering
* Procedure: modest blood pressure lowering


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: acute symptomatic ischemic stroke having relevant lesion on DWI(Diffusion weighted image) MRI 7 days after and 42 days within onset. relevant stenosis(more than 50%) or occlusion from MCA(middle cerebral artery)(M1) to distal of ICA(internal carotid artery ) on MR(Magnetic resonance) angiogram or CT angiogram. mean systolic blood pressure>=140mmHg or taking antihypertensive drug on screening. Exclusion Criteria: taking more than 3 antihypertensive drugs and mean systolic blood pressure>=150mmHg on screening. history of recent thrombolysis but stenosis or occlusion remained after thrombolysis. evidence of orthostatic hypotension suspicious embolic cerebrovascular stenosis planned state of cerebrovascular surgery or angioplasty or stent 7 months within screening. severe stroke-NIHSS>=16 mean systolic blood pressure>=200mmHg which is not able to control on screening. abnormal blood test finding (abnormal LFT(liver function test), anemia, renal insufficiency) pregnant or breast-feeding severe stroke sequela or medical problem suspicious secondary hypertension disease causing edema or significant ankle edema on screening. severe heart failure which correspond to NYHA (New York Heart Association )heart failure classification class III or IV. inappropriate condition determined by investigator Patient who do not have FLAIR image on or two months prior to screening.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aggressive BP lowering<br>Lowering of systolic blood pressure between 110mmHg and 120mmHg during study period | Procedure: Aggressive BP lowering<br>* adjust the amount and number of antihypertensive drugs to lowering of systolic blood pressure to target level<br>* Other names: Aggressive BP control;|
| Active Comparator: Modest BP lowering<br>Lowering of systolic blood pressure between 130mmHg and 140mmHg | Procedure: modest blood pressure lowering<br>* adjust the amount and number of antihypertensive drugs<br>* Other names: Modest BP control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ischemic Lesion Volume Change in the Whole Forebrain on Fluid Attenuation Inversion Recovery (FLAIR) Magnetic Resonance Imaging (MRI) | The difference between final ischemic lesions volume and base ischemic lesions of both hemisphere on FLAIR MRI | Screening to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of the Ischemic Lesion Volume in Cerebral Hemisphere on FLAIR From Screening to Week 24 in FAS Population | the difference between final ischemic lesions volume and base ischemic lesions in the territory of symptomatic intracranial disease on FLAIR MRI | 24 weeks | 
| The Number of Patients With New Ischemic Lesion in the Whole Forebrain on FLAIR MRI |  | 24 weeks | 
| Number of Participants With Cardiovascular Events From Screening to Week 24 in ITT Population. |  | 24 weeks | 
| Total Number of Cardiovascular Events Form Screening to Week 24 in ITT Population. |  | 24 Week | 
| Number of Participants With Vascular Death From Screening to Week 24 in ITT Population. |  | 24 Weeks | 
| Number of Participants With Adverse Events | Number of Participants with Adverse Events | 24 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blood Pressure, Atherosclerosis, Brain Ischemia