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

Primary Purpose

Stroke, Ischemic, Atherosclerosis, Cerebral

Status
Recruiting
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Atorvastatin Calcium
Atorvastatin Calcium
Probucol
PCSK9 inhibitor
Sponsored by
General Hospital of Shenyang Military Region
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stroke, Ischemic

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • General Hospital of ShenYang Military RegionRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Routine-dose statin group

high-dose statin or PCSK9 inhibitor group

Arm Description

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

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.

Outcomes

Primary Outcome Measures

Changes in remodeling index after the statin treatment
remodeling index: crimed vessel area/normal vessel area on high-resolution MRI
Changes in plaque burden after the statin treatment
plaque burden: crimed vessel wall area/crimed vessel area on high-resolution MRI
Changes plaque composition in after the statin treatment
plaque composition: lipid core and fiber tissue of plaque on high-resolution MRI

Secondary Outcome Measures

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

Full Information

First Posted
November 13, 2018
Last Updated
February 15, 2023
Sponsor
General Hospital of Shenyang Military Region
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1. Study Identification

Unique Protocol Identification Number
NCT03753555
Brief Title
The Effect of InTensive Statin in Ischemic Stroke With inTracranial Atherosclerotic Plaques
Acronym
INSIST-HRMRI
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 1, 2018 (Actual)
Primary Completion Date
November 30, 2024 (Anticipated)
Study Completion Date
November 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
General Hospital of Shenyang Military Region

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stroke, Ischemic, Atherosclerosis, Cerebral

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Routine-dose statin group
Arm Type
Active Comparator
Arm Description
Routine-dose statin group will be gaven the treatment of atorvastatin 20mg Qd for 12 months
Arm Title
high-dose statin or PCSK9 inhibitor group
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Atorvastatin Calcium
Intervention Description
20mg Qd for 12 months
Intervention Type
Drug
Intervention Name(s)
Atorvastatin Calcium
Intervention Description
40-80mg Qd for 6 months
Intervention Type
Drug
Intervention Name(s)
Probucol
Intervention Description
0.5g Bid for 6 months
Intervention Type
Drug
Intervention Name(s)
PCSK9 inhibitor
Intervention Description
Evolocumab 140mg subcutaneously injected, twice each month
Primary Outcome Measure Information:
Title
Changes in remodeling index after the statin treatment
Description
remodeling index: crimed vessel area/normal vessel area on high-resolution MRI
Time Frame
baseline, 6 months, 12 months after treatment
Title
Changes in plaque burden after the statin treatment
Description
plaque burden: crimed vessel wall area/crimed vessel area on high-resolution MRI
Time Frame
baseline, 6 months, 12 months after treatment
Title
Changes plaque composition in after the statin treatment
Description
plaque composition: lipid core and fiber tissue of plaque on high-resolution MRI
Time Frame
baseline, 6 months, 12 months after treatment
Secondary Outcome Measure Information:
Title
level of serum bio-markers compared with baseline
Description
Serum level of LDL、hs-CRP、sLOX1 and oxLDL
Time Frame
6 months
Title
level of serum bio-markers compared with baseline
Description
Serum level of LDL、hs-CRP、sLOX1 and oxLDL
Time Frame
12 months
Title
mRS (0-2)
Description
proportion of mRS (0-2)
Time Frame
6 months
Title
mRS (0-2)
Description
proportion of mRS (0-2)
Time Frame
12 months
Title
vascular events
Description
incidence of Transient ischemic attack, stroke or other vascular events
Time Frame
6 months
Title
vascular events
Description
incidence of Transient ischemic attack, stroke or other vascular events
Time Frame
12 months
Title
abnormal test data
Description
incidence of abnormal liver function or muscle enzyme levels
Time Frame
12 months
Title
any adverse event
Description
incidence of adverse event
Time Frame
12 months
Title
death of any causes
Description
proportion of death
Time Frame
12months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patient age between 18-80 years Time of onset: within 1 week NIHSS score ≤12 Acute ischemic stroke confirmed by head CT or MRI Premorbid mRS ≤1 The degree of stenosis of carotid artery, vertebral artery and intracranial portion of internal carotid artery on the lesion side <50% 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 Signed informed consent Exclusion Criteria: Intracranial hemorrhage found by head CT Stroke attributable to cardioembolic origin (atrial fibrillation, valvular heart disease, aortic arch atherosclerosis) Severe hepatic or renal dysfunction Pregnant females Abnormal elevation of creatine phosphokinase Expected stent angioplasty Blood sugar is out of control Receiving statins within 1 month before onset Obstinate hypertension with more than 140/90 mmHg after medication Not willing and able to comply with scheduled visits, lifestyle guidelines, treatment plan, laboratory tests, and other study procedures Unsuitable for this clinical studies assessed by researcher
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xinhong Wang, Doctor
Phone
15309885658
Ext
024-28897512
Email
450341972@qq.com
First Name & Middle Initial & Last Name or Official Title & Degree
Yu Cui, Master
Phone
18842398646
Ext
024-28897512
Email
314486939@qq.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Huisheng Chen, Doctor
Organizational Affiliation
Neurology Department
Official's Role
Study Chair
Facility Information:
Facility Name
General Hospital of ShenYang Military Region
City
ShenYang
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cheng Xia, Ph.D
Email
xiacheng1975@sina.com

12. IPD Sharing Statement

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

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