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Intracranial Hemorrhage Risk of Intensive Statin in Acute Ischemic Stroke With Cerebral Microbleeds

Primary Purpose

Acute Ischemic Stroke, Cerebral Microbleeds

Status
Not yet recruiting
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Atorvastatin Calcium tablets 80mg
Atorvastatin Calcium tablets 20mg
Sponsored by
Sichuan Provincial People's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Acute Ischemic Stroke focused on measuring Acute Ischemic Stroke, Intracranial Hemorrhage Risk, Cerebral Microbleeds, Intensive Statin Therapy

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Patients with a non-cardioembolic ischemic stroke within 14 days prior to entry to the study
  2. Adults between the ages of 18 and 85
  3. Patients with cerebral microbleeds on baseline SWI imaging
  4. Patients or their legal representatives volunteer to participate and sign written informed consent

Exclusion Criteria:

  1. Patients with severe acute ischemic stroke (NIHSS score ≥21)
  2. Patients with coma (GCS score < 8)
  3. Patients with previous moderate to severe dependence (mRS score 3-5)
  4. Patients with any contraindications to CT and MRI (such as metal implants, claustrophobia, etc.)
  5. Patients who are allergic to atorvastatin or excipients
  6. Patients with intracranial hemorrhagic diseases confirmed by CT or MRI, such as cerebral hemorrhage, epidural hematoma, subdural hematoma, ventricular hemorrhage, subarachnoid hemorrhage, traumatic cerebral hemorrhage or hemorrhagic conversion of infarcts, etc
  7. Patients within 6 months after hemorrhagic stroke
  8. Patients with hemorrhagic tendency, such as abnormal coagulation function, Henoch-Schonlein purpura, platelet count less than 100×109/L or abnormal platelet function, etc
  9. Patients who are ready to undergo or have undergone intravenous thrombolysis after the onset of the disease or who require urgent or recent (within 90 days) endovascular treatment;
  10. Patients with severe hypertension (systolic blood pressure ≥ 185 mmHg or diastolic blood pressure ≥ 110 mmHg) that has not been controlled by treatment
  11. Patients with hypoglycemia (< 2.7 mmol/L) or hyperglycemia (>22.2 mmol/L)
  12. Patients with previous cerebral arteritis, brain tumor, cerebral parasitic disease, cerebral arteriovenous malformation, cerebral cavernous hemangioma, cerebral aneurysm, severe craniocerebral injury, or intracranial infection
  13. Patients with previous severe valvular heart disease, atrial fibrillation, acute myocardial infarction or interventional therapy in the past 6 months, heart failure (patients classified as class III-IV according to the New York Heart Association [NYHA]) or patients with indications for pacemaker placement but without pacemaker installation or other malignant arrhythmias
  14. Patients contraindicate to antiplatelet therapy;
  15. Patients who must use other types of statins or other types of lipid-lowering drugs such as ezetimibe
  16. Patients with severe mental disorders or dementia that are unable or unwilling to cooperate
  17. Patients with active liver disease or unexplained 2 or more abnormal liver function tests (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] ≥ 3.0× upper limit of normal [ULN])
  18. Patients with myositis, myopathy, rhabdomyolysis, or 2 or more episodes of unexplained serum creatine kinase[CK] elevation ([CK]≥5.0×ULN)
  19. Patients with other serious systemic or organic diseases that investigators believe will not allow evaluation of efficacy or are unlikely to complete the expected course of treatment and follow-up (e.g., malignancy, life expectancy < 3 years, etc.)
  20. Women who are pregnant, breastfeeding or planning to become pregnant and who do not want to use contraception
  21. Patients who participated in or are participating in other clinical trials during the 3 months prior to the study
  22. Patients who are deemed ineligible for clinical trial participation by the investigator
  23. Patients or their legal representatives do not consent to participate in this study

Sites / Locations

  • Yunyang County People's Hospital
  • Chengdu Eighth People's Hospital
  • Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital
  • Ya 'an People's Hospital
  • Zigong Third People's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

High-dose atorvastatin

Low-dose atorvastatin

Arm Description

atorvastatin calcium tablets 80 mg, quaque nocte, continue to the end of the study

atorvastatin calcium tablets 20 mg, quaque nocte, continue to the end of the study

Outcomes

Primary Outcome Measures

The incidence of hemorrhagic strokes
Changes in degree of cerebral microbleeds
The degree is divided into: mild (1-2), moderate (3-10), severe (more than 10), calculate and compare the proportions of different degrees at baseline and the end of the study

Secondary Outcome Measures

The Incidence of recurrent ischemic stroke and transient ischemic attack
The Incidence of myocardial infarction
The Incidence of cardiovascular death
The mean of serum triglycerides (TG) levels
Calculate the mean of serum TG levels for 3 years with at least 3 measurements
The mean of serum total cholesterol (TC) levels
Calculate the mean of serum TC levels for 3 years with at least 3 measurements
The mean of serum low-density lipoprotein cholesterol (LDL-C) levels
Calculate the mean of serum LDL-C levels for 3 years with at least 3 measurements
The mean of serum high-density lipoprotein cholesterol (HDL-C) levels
Calculate the mean of serum HDL-C levels for 3 years with at least 3 measurements
The variability of serum triglycerides (TG) levels
Calculate the variability of serum TG levels for 3 years with at least 3 measurements
The variability of serum total cholesterol (TC) levels
Calculate the variability of serum TC levels for 3 years with at least 3 measurements
The variability of serum low-density lipoprotein cholesterol (LDL-C) levels
Calculate the variability of serum LDL-C levels for 3 years with at least 3 measurements
The variability of serum high-density lipoprotein cholesterol (HDL-C) levels
Calculate the variability of serum HDL-C levels for 3 years with at least 3 measurements
The proportions of different degrees of CMBs at the end of the study
Calculate the proportions of different degrees of CMBs (mild, moderate and severe) at the end of the study
The correlation between the mean of serum triglycerides (TG) levels and the proportions of different degrees of CMBs
The correlation between the mean of serum total cholesterol (TC) levels and the proportions of different degrees of CMBs
The correlation between the mean of serum low-density lipoprotein cholesterol (LDL-C) levels and the proportions of different degrees of CMBs
The correlation between the mean of serum high-density lipoprotein cholesterol (HDL-C) levels and the proportions of different degrees of CMBs
The correlation between the variability of serum triglycerides (TG) levels and the proportions of different degrees of CMBs
The correlation between the variability of serum total cholesterol (TC) levels and the proportions of different degrees of CMBs
The correlation between the variability of serum low-density lipoprotein cholesterol (LDL-C) levels and the proportions of different degrees of CMBs
The correlation between the variability of serum high-density lipoprotein cholesterol (HDL-C) levels and the proportions of different degrees of CMBs

Full Information

First Posted
October 11, 2022
Last Updated
October 19, 2022
Sponsor
Sichuan Provincial People's Hospital
Collaborators
Science & Technology Department of Sichuan Province
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1. Study Identification

Unique Protocol Identification Number
NCT05589454
Brief Title
Intracranial Hemorrhage Risk of Intensive Statin in Acute Ischemic Stroke With Cerebral Microbleeds
Official Title
Intracranial Hemorrhage Risk of Intensive Statin Therapy in Patients With Acute Ischemic Stroke Combined With Cerebral Microbleeds
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
January 2023 (Anticipated)
Primary Completion Date
December 2026 (Anticipated)
Study Completion Date
June 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sichuan Provincial People's Hospital
Collaborators
Science & Technology Department of Sichuan Province

4. Oversight

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

5. Study Description

Brief Summary
This study is the first and largest secondary prevention trial about lipid-lowering therapy for acute ischemic stroke patients at high-risk of intracranial hemorrhage. The primary hypothesis of this study is: excessive reduction in serum lipid levels by intensive statin therapy in acute ischemic stroke patients with cerebral microbleeds can increase the risk of intracranial hemorrhage. This study will shed light on new clinical decisions regarding the long-term serum lipid management in these patients with dilemma in clinical practice.
Detailed Description
Cerebral microbleeds are an important subtype of cerebral small vessel diseases that have been established in approximately one third of patients with ischemic stroke and are associated with the risk of recurrent ischemic stroke, symptomatic intracranial hemorrhage, and all-cause death. In patients with ischemic stroke or transient ischemic attack, the relative and absolute risks of intracranial hemorrhage increase more rapidly than the risk of ischemic stroke with the increase of cerebral microbleeds burden, but the absolute incidence of ischemic stroke is still higher than that of cerebral hemorrhage. It has been generally accepted that statins can effectively prevent recurrent ischemic stroke by reducing serum lipid levels. However, both low serum lipid levels and high dose of statins are clear risk factors for intracerebral hemorrhage, and the reduction of major serum lipid levels may increase the risk of cerebral microbleeds. Of note, the risk of statin mediated hemorrhage appears to depend on the degree of lipid reduction rather than statin use per se. These observations raise concerns about the safety of lipid-lowering therapy, especially intensive lipid-lowering therapy, in patients with acute ischemic stroke and cerebral microbleeds who are at high risk for future intracranial hemorrhage. It is still not clear that how to carry on the proper management of serum lipid levels in this particular population to reduce the recurrence of ischemic events as well as hemorrhagic events, for there is still a lack of clinical studies to explore the risk and benefit of different doses of statins to achieve different degrees of lipid regulation. So, if it is proved that excessive reduction in serum lipid levels by intensive statin therapy in acute ischemic stroke patients with cerebral microbleeds can increase the risk of future intracranial hemorrhage, we will inform new clinical decisions regarding the long-term lipid management in these patients with dilemma in clinical practice.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Ischemic Stroke, Cerebral Microbleeds
Keywords
Acute Ischemic Stroke, Intracranial Hemorrhage Risk, Cerebral Microbleeds, Intensive Statin Therapy

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
High-dose atorvastatin
Arm Type
Experimental
Arm Description
atorvastatin calcium tablets 80 mg, quaque nocte, continue to the end of the study
Arm Title
Low-dose atorvastatin
Arm Type
Active Comparator
Arm Description
atorvastatin calcium tablets 20 mg, quaque nocte, continue to the end of the study
Intervention Type
Drug
Intervention Name(s)
Atorvastatin Calcium tablets 80mg
Other Intervention Name(s)
ALe produced by Jialin pharmaceutical company
Intervention Description
Atorvastatin calcium tablets 4 pills (80 mg) will be given at a fixed time every night (24 ± 1 h between two doses) , orally, until the end of follow-up
Intervention Type
Drug
Intervention Name(s)
Atorvastatin Calcium tablets 20mg
Other Intervention Name(s)
ALe produced by Jialin pharmaceutical company
Intervention Description
Atorvastatin calcium tablets 1 pill (20 mg) will be given at a fixed time every night (24 ± 1 h between two doses) , orally, until the end of follow-up
Primary Outcome Measure Information:
Title
The incidence of hemorrhagic strokes
Time Frame
From date of randomization until the date of the first occurrence of hemorrhagic stroke, assessed up to 36 months
Title
Changes in degree of cerebral microbleeds
Description
The degree is divided into: mild (1-2), moderate (3-10), severe (more than 10), calculate and compare the proportions of different degrees at baseline and the end of the study
Time Frame
From date of randomization until the end of the study, assessed up to 36 months
Secondary Outcome Measure Information:
Title
The Incidence of recurrent ischemic stroke and transient ischemic attack
Time Frame
From date of randomization until the date of the first recurrent of ischemic stroke or the first occurrence of transient ischemic attack, assessed up to 36 months
Title
The Incidence of myocardial infarction
Time Frame
From date of randomization until the date of the first occurrence of myocardial infarction, assessed up to 36 months
Title
The Incidence of cardiovascular death
Time Frame
From date of randomization until the date of cardiovascular death, assessed up to 36 months
Title
The mean of serum triglycerides (TG) levels
Description
Calculate the mean of serum TG levels for 3 years with at least 3 measurements
Time Frame
From date of randomization until the end of the study, assessed up to 36 months
Title
The mean of serum total cholesterol (TC) levels
Description
Calculate the mean of serum TC levels for 3 years with at least 3 measurements
Time Frame
From date of randomization until the end of the study, assessed up to 36 months
Title
The mean of serum low-density lipoprotein cholesterol (LDL-C) levels
Description
Calculate the mean of serum LDL-C levels for 3 years with at least 3 measurements
Time Frame
From date of randomization until the end of the study, assessed up to 36 months
Title
The mean of serum high-density lipoprotein cholesterol (HDL-C) levels
Description
Calculate the mean of serum HDL-C levels for 3 years with at least 3 measurements
Time Frame
From date of randomization until the end of the study, assessed up to 36 months
Title
The variability of serum triglycerides (TG) levels
Description
Calculate the variability of serum TG levels for 3 years with at least 3 measurements
Time Frame
From date of randomization until the end of the study, assessed up to 36 months
Title
The variability of serum total cholesterol (TC) levels
Description
Calculate the variability of serum TC levels for 3 years with at least 3 measurements
Time Frame
From date of randomization until the end of the study, assessed up to 36 months
Title
The variability of serum low-density lipoprotein cholesterol (LDL-C) levels
Description
Calculate the variability of serum LDL-C levels for 3 years with at least 3 measurements
Time Frame
From date of randomization until the end of the study, assessed up to 36 months
Title
The variability of serum high-density lipoprotein cholesterol (HDL-C) levels
Description
Calculate the variability of serum HDL-C levels for 3 years with at least 3 measurements
Time Frame
From date of randomization until the end of the study, assessed up to 36 months
Title
The proportions of different degrees of CMBs at the end of the study
Description
Calculate the proportions of different degrees of CMBs (mild, moderate and severe) at the end of the study
Time Frame
From date of randomization until the end of the study, assessed up to 36 months
Title
The correlation between the mean of serum triglycerides (TG) levels and the proportions of different degrees of CMBs
Time Frame
From date of randomization until the end of the study, assessed up to 36 months
Title
The correlation between the mean of serum total cholesterol (TC) levels and the proportions of different degrees of CMBs
Time Frame
From date of randomization until the end of the study, assessed up to 36 months
Title
The correlation between the mean of serum low-density lipoprotein cholesterol (LDL-C) levels and the proportions of different degrees of CMBs
Time Frame
From date of randomization until the end of the study, assessed up to 36 months
Title
The correlation between the mean of serum high-density lipoprotein cholesterol (HDL-C) levels and the proportions of different degrees of CMBs
Time Frame
From date of randomization until the end of the study, assessed up to 36 months
Title
The correlation between the variability of serum triglycerides (TG) levels and the proportions of different degrees of CMBs
Time Frame
From date of randomization until the end of the study, assessed up to 36 months
Title
The correlation between the variability of serum total cholesterol (TC) levels and the proportions of different degrees of CMBs
Time Frame
From date of randomization until the end of the study, assessed up to 36 months
Title
The correlation between the variability of serum low-density lipoprotein cholesterol (LDL-C) levels and the proportions of different degrees of CMBs
Time Frame
From date of randomization until the end of the study, assessed up to 36 months
Title
The correlation between the variability of serum high-density lipoprotein cholesterol (HDL-C) levels and the proportions of different degrees of CMBs
Time Frame
From date of randomization until the end of the study, assessed up to 36 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with a non-cardioembolic ischemic stroke within 14 days prior to entry to the study Adults between the ages of 18 and 85 Patients with cerebral microbleeds on baseline SWI imaging Patients or their legal representatives volunteer to participate and sign written informed consent Exclusion Criteria: Patients with severe acute ischemic stroke (NIHSS score ≥21) Patients with coma (GCS score < 8) Patients with previous moderate to severe dependence (mRS score 3-5) Patients with any contraindications to CT and MRI (such as metal implants, claustrophobia, etc.) Patients who are allergic to atorvastatin or excipients Patients with intracranial hemorrhagic diseases confirmed by CT or MRI, such as cerebral hemorrhage, epidural hematoma, subdural hematoma, ventricular hemorrhage, subarachnoid hemorrhage, traumatic cerebral hemorrhage or hemorrhagic conversion of infarcts, etc Patients within 6 months after hemorrhagic stroke Patients with hemorrhagic tendency, such as abnormal coagulation function, Henoch-Schonlein purpura, platelet count less than 100×109/L or abnormal platelet function, etc Patients who are ready to undergo or have undergone intravenous thrombolysis after the onset of the disease or who require urgent or recent (within 90 days) endovascular treatment; Patients with severe hypertension (systolic blood pressure ≥ 185 mmHg or diastolic blood pressure ≥ 110 mmHg) that has not been controlled by treatment Patients with hypoglycemia (< 2.7 mmol/L) or hyperglycemia (>22.2 mmol/L) Patients with previous cerebral arteritis, brain tumor, cerebral parasitic disease, cerebral arteriovenous malformation, cerebral cavernous hemangioma, cerebral aneurysm, severe craniocerebral injury, or intracranial infection Patients with previous severe valvular heart disease, atrial fibrillation, acute myocardial infarction or interventional therapy in the past 6 months, heart failure (patients classified as class III-IV according to the New York Heart Association [NYHA]) or patients with indications for pacemaker placement but without pacemaker installation or other malignant arrhythmias Patients contraindicate to antiplatelet therapy; Patients who must use other types of statins or other types of lipid-lowering drugs such as ezetimibe Patients with severe mental disorders or dementia that are unable or unwilling to cooperate Patients with active liver disease or unexplained 2 or more abnormal liver function tests (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] ≥ 3.0× upper limit of normal [ULN]) Patients with myositis, myopathy, rhabdomyolysis, or 2 or more episodes of unexplained serum creatine kinase[CK] elevation ([CK]≥5.0×ULN) Patients with other serious systemic or organic diseases that investigators believe will not allow evaluation of efficacy or are unlikely to complete the expected course of treatment and follow-up (e.g., malignancy, life expectancy < 3 years, etc.) Women who are pregnant, breastfeeding or planning to become pregnant and who do not want to use contraception Patients who participated in or are participating in other clinical trials during the 3 months prior to the study Patients who are deemed ineligible for clinical trial participation by the investigator Patients or their legal representatives do not consent to participate in this study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jialing Zhao, MD
Phone
+8618113137196
Email
jailynyy@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jialing Zhao, MD
Organizational Affiliation
Departement of Neurology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Yang Xiang, MD
Organizational Affiliation
Departement of Neurology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital
Official's Role
Study Director
Facility Information:
Facility Name
Yunyang County People's Hospital
City
Chongqing
State/Province
Chongqing
ZIP/Postal Code
404599
Country
China
Facility Name
Chengdu Eighth People's Hospital
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610017
Country
China
Facility Name
Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610072
Country
China
Facility Name
Ya 'an People's Hospital
City
Ya'an
State/Province
Sichuan
ZIP/Postal Code
625000
Country
China
Facility Name
Zigong Third People's Hospital
City
Zigong
State/Province
Sichuan
ZIP/Postal Code
643021
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No

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Intracranial Hemorrhage Risk of Intensive Statin in Acute Ischemic Stroke With Cerebral Microbleeds

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