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

The Effect of InTensive Statin in Ischemic Stroke With inTracranial Atherosclerotic Plaques: a Prospective, Random, Single-center Study Based on High Resolution Magnetic Resonance Imaging

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.

Study Overview

• Status: Recruiting
• Conditions: Stroke, Ischemic; Atherosclerosis, Cerebral
• Intervention / Treatment: Drug: Atorvastatin Calcium; Drug: Atorvastatin Calcium; Drug: Probucol; Drug: PCSK9 inhibitor

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Xinhong Wang, Doctor; Phone Number: 024-28897512 15309885658; Email: 450341972@qq.com
• Study Contact Backup: Name: Yu Cui, Master; Phone Number: 024-28897512 18842398646; Email: 314486939@qq.com

Study Locations

• China
  • Shenyang, China
    • Recruiting
    • General Hospital of Shenyang Military Region
    • Contact: Cheng Xia, Ph.D; Email: xiacheng1975@sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Routine-dose statin group; Routine-dose statin group will be gaven the treatment of atorvastatin 20mg Qd for 12 months	Drug: Atorvastatin Calcium; 20mg Qd for 12 months; Drug: Atorvastatin Calcium; 40-80mg Qd for 6 months
Experimental: high-dose statin or PCSK9 inhibitor group; 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.	Drug: Atorvastatin Calcium; 20mg Qd for 12 months; Drug: Atorvastatin Calcium; 40-80mg Qd for 6 months; Drug: Probucol; 0.5g Bid for 6 months; Drug: PCSK9 inhibitor; Evolocumab 140mg subcutaneously injected, twice each month

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in remodeling index after the statin treatment	remodeling index: crimed vessel area/normal vessel area on high-resolution MRI	baseline, 6 months, 12 months after treatment
Changes in plaque burden after the statin treatment	plaque burden: crimed vessel wall area/crimed vessel area on high-resolution MRI	baseline, 6 months, 12 months after treatment
Changes plaque composition in after the statin treatment	plaque composition: lipid core and fiber tissue of plaque on high-resolution MRI	baseline, 6 months, 12 months after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
level of serum bio-markers compared with baseline	Serum level of LDL、hs-CRP、sLOX1 and oxLDL	6 months
level of serum bio-markers compared with baseline	Serum level of LDL、hs-CRP、sLOX1 and oxLDL	12 months
mRS (0-2)	proportion of mRS (0-2)	6 months
mRS (0-2)	proportion of mRS (0-2)	12 months
vascular events	incidence of Transient ischemic attack, stroke or other vascular events	6 months
vascular events	incidence of Transient ischemic attack, stroke or other vascular events	12 months
abnormal test data	incidence of abnormal liver function or muscle enzyme levels	12 months
any adverse event	incidence of adverse event	12 months
death of any causes	proportion of death	12months

Collaborators and Investigators

• Sponsor: General Hospital of Shenyang Military Region
• Investigators: Study Chair: Huisheng Chen, Doctor, Neurology department

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2018
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2027

Study Registration Dates

• First Submitted: November 13, 2018
• First Submitted That Met QC Criteria: November 22, 2018
• First Posted (Actual): November 27, 2018

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Intracranial Arterial Diseases; Stroke; Ischemic Stroke; Intracranial Arteriosclerosis; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fatty Acids; Lipids; Azoles; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Phenols; Benzene Derivatives; Pyrroles; Heptanoic Acids; Atorvastatin; Probucol
• Other Study ID Numbers: k（2018）44

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No