The Effect of InTensive Statin in Ischemic Stroke With inTracranial Atherosclerotic Plaques (INSIST-HRMRI)

General Hospital of Northern Theater Command of Chinese People's Liberation Army

Status and phase: Enrolling; Phase 4

Conditions: Atherosclerosis, Cerebral; Stroke, Ischemic

Treatments: Drug: Probucol; Drug: Atorvastatin Calcium; Drug: PCSK9 inhibitor

Study type: Interventional

Funder types: Other

Identifiers

NCT03753555

k（2018）44

Details and patient eligibility

About

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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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100 participants in 2 patient groups

Routine-dose statin group

Active Comparator group

Description:

Routine-dose statin group will be gaven the treatment of atorvastatin 20mg Qd for 12 months

Treatment:

Drug: Atorvastatin Calcium

Drug: Atorvastatin Calcium

high-dose statin or PCSK9 inhibitor group

Experimental group

Description:

high-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.

Treatment:

Drug: PCSK9 inhibitor

Drug: Atorvastatin Calcium

Drug: Atorvastatin Calcium

Drug: Probucol