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The Effect of InTensive Statin in Ischemic Stroke With inTracranial Atherosclerotic Plaques

Phase 4
Recruiting
Conditions
Stroke, Ischemic
Atherosclerosis, Cerebral
Interventions
Registration Number
NCT03753555
Lead Sponsor
General Hospital of Shenyang Military Region
Brief Summary

Intracranial atherosclerotic disease is the most common cause of ischemic stroke that is directly attributed to the progression or rupture of intracranial high-risk plaque in Asia. Many studies mainly from Euro-American population with a focus on extracranial carotid plaque have fully demonstrated the advantages of intensive statin therapy on stabilizing or reversing plaque burden, reversing plaque composition presenting that lipid-rich necrotic core (LRNC) is gradually replaced by fibrous tissue, and even reversing pattern of arterial remodeling to reduce the occurrence of cerebrovascular events. Yet, direct evidence of the effect of intensive statin therapy on intracranial atherosclerotic plaques is lacking and the effect of statin intensity and duration on intracranial plaque burden and composition is still unclear. High resolution magnetic resonance imaging (HRMRI) is a new and non-invasive technique that enable to assess the morphologic characteristics of vascular wall and plaque composition of intracranial artery. Based on above discussion, the investigators conduct this study to further determine the effect of intensive statin in ischemic stroke with intracranial atherosclerotic plaques.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
100
Inclusion Criteria
  1. Patient age between 18-80 years
  2. Time of onset: within 1 week
  3. NIHSS score ≤12
  4. Acute ischemic stroke confirmed by head CT or MRI
  5. Premorbid mRS ≤1
  6. The degree of stenosis of carotid artery, vertebral artery and intracranial portion of internal carotid artery on the lesion side <50%
  7. The culprit plaque or possible culprit plaque with plaque burden of 40% or more found by HRMRI in the proximal part of the middle cerebral artery M1 segment or basilar artery of ipsilateral lesion
  8. Signed informed consent
Exclusion Criteria
  1. Intracranial hemorrhage found by head CT
  2. Stroke attributable to cardioembolic origin (atrial fibrillation, valvular heart disease, aortic arch atherosclerosis)
  3. Severe hepatic or renal dysfunction
  4. Pregnant females
  5. Abnormal elevation of creatine phosphokinase
  6. Expected stent angioplasty
  7. Blood sugar is out of control
  8. Receiving statins within 1 month before onset
  9. Obstinate hypertension with more than 140/90 mmHg after medication
  10. Not willing and able to comply with scheduled visits, lifestyle guidelines, treatment plan, laboratory tests, and other study procedures
  11. Unsuitable for this clinical studies assessed by researcher

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Routine-dose statin groupAtorvastatin CalciumRoutine-dose statin group will be gaven the treatment of atorvastatin 20mg Qd for 12 months
high-dose statin or PCSK9 inhibitor groupAtorvastatin Calciumhigh-dose statin group will be gaven the treatment of atorvastatin 40-80mg Qd till 6 months at the moment the subjects will be followed up to determine plaques status by HRMRI examination, among which the subjects presenting culprit plaque progression with the significant increasing of plaque burden including intraplaque hemorrhage will be again randomized into two groups at a ratio of 1:1 as followed: atorvastatin-probucol group will be administrated atorvastatin 40-80mg Qd plus probucol 0.5g Bid till 12 months, the other group will maintain the original scheme till 12 months. PCSK9 inhibitor group will receive the subcutaneous injection of Evolocumab (140mg, 2 / month) for one year.
high-dose statin or PCSK9 inhibitor groupPCSK9 inhibitorhigh-dose statin group will be gaven the treatment of atorvastatin 40-80mg Qd till 6 months at the moment the subjects will be followed up to determine plaques status by HRMRI examination, among which the subjects presenting culprit plaque progression with the significant increasing of plaque burden including intraplaque hemorrhage will be again randomized into two groups at a ratio of 1:1 as followed: atorvastatin-probucol group will be administrated atorvastatin 40-80mg Qd plus probucol 0.5g Bid till 12 months, the other group will maintain the original scheme till 12 months. PCSK9 inhibitor group will receive the subcutaneous injection of Evolocumab (140mg, 2 / month) for one year.
high-dose statin or PCSK9 inhibitor groupProbucolhigh-dose statin group will be gaven the treatment of atorvastatin 40-80mg Qd till 6 months at the moment the subjects will be followed up to determine plaques status by HRMRI examination, among which the subjects presenting culprit plaque progression with the significant increasing of plaque burden including intraplaque hemorrhage will be again randomized into two groups at a ratio of 1:1 as followed: atorvastatin-probucol group will be administrated atorvastatin 40-80mg Qd plus probucol 0.5g Bid till 12 months, the other group will maintain the original scheme till 12 months. PCSK9 inhibitor group will receive the subcutaneous injection of Evolocumab (140mg, 2 / month) for one year.
Primary Outcome Measures
NameTimeMethod
Changes in remodeling index after the statin treatmentbaseline, 6 months, 12 months after treatment

remodeling index: crimed vessel area/normal vessel area on high-resolution MRI

Changes in plaque burden after the statin treatmentbaseline, 6 months, 12 months after treatment

plaque burden: crimed vessel wall area/crimed vessel area on high-resolution MRI

Changes plaque composition in after the statin treatmentbaseline, 6 months, 12 months after treatment

plaque composition: lipid core and fiber tissue of plaque on high-resolution MRI

Secondary Outcome Measures
NameTimeMethod
any adverse event12 months

incidence of adverse event

death of any causes12months

proportion of death

level of serum bio-markers compared with baseline12 months

Serum level of LDL、hs-CRP、sLOX1 and oxLDL

mRS (0-2)12 months

proportion of mRS (0-2)

vascular events12 months

incidence of Transient ischemic attack, stroke or other vascular events

abnormal test data12 months

incidence of abnormal liver function or muscle enzyme levels

Trial Locations

Locations (1)

General Hospital of ShenYang Military Region

🇨🇳

ShenYang, China

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