<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03753555</url>
  </required_header>
  <id_info>
    <org_study_id>k（2018）44</org_study_id>
    <nct_id>NCT03753555</nct_id>
  </id_info>
  <brief_title>The Effect of InTensive Statin in Ischemic Stroke With inTracranial Atherosclerotic Plaques</brief_title>
  <acronym>INSIST-HRMRI</acronym>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>General Hospital of Shenyang Military Region</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>General Hospital of Shenyang Military Region</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Intracranial atherosclerotic disease is the most common cause of ischemic stroke that is&#xD;
      directly attributed to the progression or rupture of intracranial high-risk plaque in Asia.&#xD;
      Many studies mainly from Euro-American population with a focus on extracranial carotid plaque&#xD;
      have fully demonstrated the advantages of intensive statin therapy on stabilizing or&#xD;
      reversing plaque burden, reversing plaque composition presenting that lipid-rich necrotic&#xD;
      core (LRNC) is gradually replaced by fibrous tissue, and even reversing pattern of arterial&#xD;
      remodeling to reduce the occurrence of cerebrovascular events. Yet, direct evidence of the&#xD;
      effect of intensive statin therapy on intracranial atherosclerotic plaques is lacking and the&#xD;
      effect of statin intensity and duration on intracranial plaque burden and composition is&#xD;
      still unclear. High resolution magnetic resonance imaging (HRMRI) is a new and non-invasive&#xD;
      technique that enable to assess the morphologic characteristics of vascular wall and plaque&#xD;
      composition of intracranial artery. Based on above discussion, the investigators conduct this&#xD;
      study to further determine the effect of intensive statin in ischemic stroke with&#xD;
      intracranial atherosclerotic plaques.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 1, 2018</start_date>
  <completion_date type="Anticipated">November 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">November 30, 2024</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in remodeling index after the statin treatment</measure>
    <time_frame>baseline, 6 months, 12 months after treatment</time_frame>
    <description>remodeling index: crimed vessel area/normal vessel area on high-resolution MRI</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in plaque burden after the statin treatment</measure>
    <time_frame>baseline, 6 months, 12 months after treatment</time_frame>
    <description>plaque burden: crimed vessel wall area/crimed vessel area on high-resolution MRI</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes plaque composition in after the statin treatment</measure>
    <time_frame>baseline, 6 months, 12 months after treatment</time_frame>
    <description>plaque composition: lipid core and fiber tissue of plaque on high-resolution MRI</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>level of serum bio-markers compared with baseline</measure>
    <time_frame>6 months</time_frame>
    <description>Serum level of LDL、hs-CRP、sLOX1 and oxLDL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>level of serum bio-markers compared with baseline</measure>
    <time_frame>12 months</time_frame>
    <description>Serum level of LDL、hs-CRP、sLOX1 and oxLDL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>mRS (0-2)</measure>
    <time_frame>6 months</time_frame>
    <description>proportion of mRS (0-2)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>mRS (0-2)</measure>
    <time_frame>12 months</time_frame>
    <description>proportion of mRS (0-2)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>vascular events</measure>
    <time_frame>6 months</time_frame>
    <description>incidence of Transient ischemic attack, stroke or other vascular events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>vascular events</measure>
    <time_frame>12 months</time_frame>
    <description>incidence of Transient ischemic attack, stroke or other vascular events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>abnormal test data</measure>
    <time_frame>12 months</time_frame>
    <description>incidence of abnormal liver function or muscle enzyme levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>any adverse event</measure>
    <time_frame>12 months</time_frame>
    <description>incidence of adverse event</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>death of any causes</measure>
    <time_frame>12months</time_frame>
    <description>proportion of death</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Stroke, Ischemic</condition>
  <condition>Atherosclerosis, Cerebral</condition>
  <arm_group>
    <arm_group_label>Routine-dose statin group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Routine-dose statin group will be gaven the treatment of atorvastatin 20mg Qd for 12 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>high-dose statin or PCSK9 inhibitor group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <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.&#xD;
PCSK9 inhibitor group will receive the subcutaneous injection of Evolocumab (140mg, 2 / month) for one year.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atorvastatin Calcium</intervention_name>
    <description>20mg Qd for 12 months</description>
    <arm_group_label>Routine-dose statin group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atorvastatin Calcium</intervention_name>
    <description>40-80mg Qd for 6 months</description>
    <arm_group_label>high-dose statin or PCSK9 inhibitor group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Probucol</intervention_name>
    <description>0.5g Bid for 6 months</description>
    <arm_group_label>high-dose statin or PCSK9 inhibitor group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PCSK9 inhibitor</intervention_name>
    <description>Evolocumab 140mg subcutaneously injected, twice each month</description>
    <arm_group_label>high-dose statin or PCSK9 inhibitor group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patient age between 18-80 years&#xD;
&#xD;
          2. Time of onset: within 1 week&#xD;
&#xD;
          3. NIHSS score ≤12&#xD;
&#xD;
          4. Acute ischemic stroke confirmed by head CT or MRI&#xD;
&#xD;
          5. Premorbid mRS ≤1&#xD;
&#xD;
          6. The degree of stenosis of carotid artery, vertebral artery and intracranial portion of&#xD;
             internal carotid artery on the lesion side &lt;50%&#xD;
&#xD;
          7. The culprit plaque or possible culprit plaque with plaque burden of 40% or more found&#xD;
             by HRMRI in the proximal part of the middle cerebral artery M1 segment or basilar&#xD;
             artery of ipsilateral lesion&#xD;
&#xD;
          8. Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Intracranial hemorrhage found by head CT&#xD;
&#xD;
          2. Stroke attributable to cardioembolic origin (atrial fibrillation, valvular heart&#xD;
             disease, aortic arch atherosclerosis)&#xD;
&#xD;
          3. Severe hepatic or renal dysfunction&#xD;
&#xD;
          4. Pregnant females&#xD;
&#xD;
          5. Abnormal elevation of creatine phosphokinase&#xD;
&#xD;
          6. Expected stent angioplasty&#xD;
&#xD;
          7. Blood sugar is out of control&#xD;
&#xD;
          8. Receiving statins within 1 month before onset&#xD;
&#xD;
          9. Obstinate hypertension with more than 140/90 mmHg after medication&#xD;
&#xD;
         10. Not willing and able to comply with scheduled visits, lifestyle guidelines, treatment&#xD;
             plan, laboratory tests, and other study procedures&#xD;
&#xD;
         11. Unsuitable for this clinical studies assessed by researcher&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Huisheng Chen, Doctor</last_name>
    <role>Study Chair</role>
    <affiliation>Neurology Department</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Xinhong Wang, Doctor</last_name>
    <phone>15309885658</phone>
    <phone_ext>024-28897512</phone_ext>
    <email>450341972@qq.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Yu Cui, Master</last_name>
    <phone>18842398646</phone>
    <phone_ext>024-28897512</phone_ext>
    <email>314486939@qq.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>General Hospital of ShenYang Military Region</name>
      <address>
        <city>ShenYang</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Cheng Xia, Ph.D</last_name>
      <email>xiacheng1975@sina.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>November 13, 2018</study_first_submitted>
  <study_first_submitted_qc>November 22, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 27, 2018</study_first_posted>
  <last_update_submitted>February 15, 2023</last_update_submitted>
  <last_update_submitted_qc>February 15, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 17, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>General Hospital of Shenyang Military Region</investigator_affiliation>
    <investigator_full_name>Hui-Sheng Chen</investigator_full_name>
    <investigator_title>Department Chairman</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
    <mesh_term>Ischemic Stroke</mesh_term>
    <mesh_term>Intracranial Arteriosclerosis</mesh_term>
    <mesh_term>Atherosclerosis</mesh_term>
    <mesh_term>Ischemia</mesh_term>
    <mesh_term>Plaque, Atherosclerotic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Calcium, Dietary</mesh_term>
    <mesh_term>Atorvastatin</mesh_term>
    <mesh_term>Probucol</mesh_term>
    <mesh_term>PCSK9 Inhibitors</mesh_term>
    <mesh_term>Calcium</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03753555
org study id: k（2018）44
nct id: NCT03753555
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Changes in remodeling index after the statin treatment
time frame: baseline, 6 months, 12 months after treatment
description: remodeling index: crimed vessel area/normal vessel area on high-resolution MRI
measure: Changes in plaque burden after the statin treatment
time frame: baseline, 6 months, 12 months after treatment
description: plaque burden: crimed vessel wall area/crimed vessel area on high-resolution MRI
measure: Changes plaque composition in after the statin treatment
time frame: baseline, 6 months, 12 months after treatment
description: plaque composition: lipid core and fiber tissue of plaque on high-resolution MRI
measure: level of serum bio-markers compared with baseline
time frame: 6 months
description: Serum level of LDL、hs-CRP、sLOX1 and oxLDL
measure: level of serum bio-markers compared with baseline
time frame: 12 months
description: Serum level of LDL、hs-CRP、sLOX1 and oxLDL
measure: mRS (0-2)
time frame: 6 months
description: proportion of mRS (0-2)
measure: mRS (0-2)
time frame: 12 months
description: proportion of mRS (0-2)
measure: vascular events
time frame: 6 months
description: incidence of Transient ischemic attack, stroke or other vascular events
measure: vascular events
time frame: 12 months
description: incidence of Transient ischemic attack, stroke or other vascular events
measure: abnormal test data
time frame: 12 months
description: incidence of abnormal liver function or muscle enzyme levels
measure: any adverse event
time frame: 12 months
description: incidence of adverse event
measure: death of any causes
time frame: 12months
description: proportion of death
arm group label: Routine-dose statin group
arm group type: Active Comparator
description: Routine-dose statin group will be gaven the treatment of atorvastatin 20mg Qd for 12 months
arm group label: high-dose statin or PCSK9 inhibitor group
arm group type: Experimental
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: Atorvastatin Calcium
description: 20mg Qd for 12 months
arm group label: Routine-dose statin group
intervention type: Drug
intervention name: Atorvastatin Calcium
description: 40-80mg Qd for 6 months
arm group label: high-dose statin or PCSK9 inhibitor group
intervention type: Drug
intervention name: Probucol
description: 0.5g Bid for 6 months
arm group label: high-dose statin or PCSK9 inhibitor group
intervention type: Drug
intervention name: PCSK9 inhibitor
description: Evolocumab 140mg subcutaneously injected, twice each month
arm group label: high-dose statin or PCSK9 inhibitor group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Huisheng Chen, Doctor
role: Study Chair
affiliation: Neurology Department
last name: Xinhong Wang, Doctor
phone: 15309885658
phone ext: 024-28897512
email: 450341972@qq.com
last name: Yu Cui, Master
phone: 18842398646
phone ext: 024-28897512
email: 314486939@qq.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: General Hospital of Shenyang Military Region
investigator full name: Hui-Sheng Chen
investigator title: Department Chairman
mesh term: Stroke
mesh term: Ischemic Stroke
mesh term: Intracranial Arteriosclerosis
mesh term: Atherosclerosis
mesh term: Ischemia
mesh term: Plaque, Atherosclerotic
mesh term: Calcium, Dietary
mesh term: Atorvastatin
mesh term: Probucol
mesh term: PCSK9 Inhibitors
mesh term: Calcium