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出境医 / 临床实验 / Study on Rosuvastatin+Ezetimibe and Rosuvastatin for LDL-C Goal in Patients With Recent Ischemic Stroke

Study on Rosuvastatin+Ezetimibe and Rosuvastatin for LDL-C Goal in Patients With Recent Ischemic Stroke

Study Description
Brief Summary:
A randomized clinical trial for the comparison of the efficacy and safety of moderate-intensity rosuvastatin plus ezetimibe versus high-intensity rosuvastatin for target LDL-C goal achievement in patients with recent ischemic stroke

Condition or disease Intervention/treatment Phase
Stroke, Ischemic Drug: Experimental: Rosuvastatin/Ezetimibe 10 Drug: Active Comparator: Rosuvastatin 20mg Phase 4

Detailed Description:

The purpose of this study is to compare the efficiency and safety on the target LDL-C goal achievement between rosuvastatin 10 mg plus ezetimibe 10 mg (rosuvastatin/ezetimibe 10/10 mg) once daily versus rosuvastatin 20 mg once daily in patients with recent ischemic stroke.

The target LDL-C goal achievement rate in patients with recent ischemic stroke has not been well studied. In particular, no clinical studies have been conducted comparing the efficacy and safety of low-dose rosuvastatin plus ezetimibe with high-dose rosuvastatin single agent for achieving target LDL-C levels.

In this trial, the investigators aim to compare the efficacy of the target LDL-C achievement between rosuvastatin 10 mg plus ezetimibe 10 mg (rosuvastatin/ezetimibe 10/10 mg) and rosuvastatin 20 mg in patients with recent ischemic stroke.

For this trial, more than 292 patients (584 total) per group will be enrolled.

Subjects who were satisfied with the inclusion/exclusion criteria of this trial and who agreed to participate in the clinical trial in writing were randomly assigned to a 1:1 ratio in the experimental group (the low-dose combination of rosuvastatin plus ezetimibe) and comparator group (high-dose rosuvastatin).

The duration of administration of the drug for clinical trials is 90 days (±14 days), and the efficacy and safety evaluation parameters are compared with baseline.

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 584 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Moderate-intensity Rosuvastatin Plus Ezetimibe Versus High-intensity Rosuvastatin for Target LDL-C Goal Achievement in Patients With Recent Ischemic Stroke: a Randomized Clinical Trial
Actual Study Start Date : September 9, 2019
Estimated Primary Completion Date : November 12, 2020
Estimated Study Completion Date : November 12, 2020
Arms and Interventions
Arm Intervention/treatment
Experimental: Rosuvastatin/Ezetimibe 10/10mg
The experimental group is orally administered with rosuvastatin 10 mg plus ezetimibe 10 mg combination once daily for 90 days.
Drug: Experimental: Rosuvastatin/Ezetimibe 10
  • Rosuvastatin/Ezetimibe 10/10mg
  • orally administered once daily for 90 days
Other Name: Rosuzet tab 10/10 mg

Active Comparator: Rosuvastatin 20mg
The comparator group is orally administered with rosuvastatin 20 mg single agent once daily for 90 days
Drug: Active Comparator: Rosuvastatin 20mg
  • Rosuvastatin 20mg
  • orally administered once daily for 90 days
Other Name: Suvast tab 20mg

Outcome Measures
Primary Outcome Measures :
  1. The percentage of subjects with LDL-C decreased more than 50% at 90days (±14 days) compared to Baseline [ Time Frame: Baseline, Visit 4(Day 90) ]
    The percentage of subjects with LDL-C decreased more than 50% at 90days (±14 days) compared to Baseline


Secondary Outcome Measures :
  1. Percentage of subjects with LDL-C less than 70 mg/dL at 90 days(±14 days) [ Time Frame: Baseline, Visit 4(Day 90) ]
    Percentage of subjects with LDL-C less than 70 mg/dL at 90 days(±14 days)

  2. The percentage of subjects with LDL-C decreased more than or less than 70 mg/dL at 90 days(±14 days) [ Time Frame: Baseline, Visit 4(Day 90) ]
    The percentage of subjects with LDL-C decreased more than or less than 70 mg/dL at 90 days(±14 days)

  3. The decrement of LDL-C at 90 days (±14 days) compared to baseline LDL-C (absolute difference and change) [ Time Frame: Baseline, Visit 4(Day 90) ]
    The decrement of LDL-C at 90 days (±14 days) compared to baseline LDL-C (absolute difference and change)

  4. The percentage of subjects achieved multiple lipid level (Total-C < 200mg/dL, LDL-C < 70mg/dL and triglyceride < 150mg /dL) [ Time Frame: Baseline, Visit 4(Day 90) ]
    The percentage of subjects achieved multiple lipid level (Total-C < 200mg/dL, LDL-C < 70mg/dL and triglyceride < 150mg /dL)

  5. Cardiovascular event rates including stroke (ischemic or hemorrhagic), coronary artery(myocardial infarction or coronary vascular reperfusion) and death related to vascular disease. [ Time Frame: Baseline to Visit 4(up to 90 days) ]
    Cardiovascular event rates including stroke (ischemic of hemorrhagic), coronary artery(myocardial infarction or coronary vascular reperfusion) and death related to vascular disease.

  6. Number of Death of all causes. [ Time Frame: Baseline to Visit 4(up to 90 days) ]
    Number of Death of all causes.

  7. Number of subjects with newly diagnosed diabetes. [ Time Frame: Visit 4(Day 90) ]
    Number of subjects with newly diagnosed diabetes.

  8. Fatigue scale measured by Fatigue Severity Scale. [ Time Frame: Screening, Visit 4(Day 90) ]
    Fatigue scale measured by Fatigue Severity Scale. (The Fatigue Severity Scale is a 9-item scale which measures the severity of fatigue and its effect on a person's activity and lifestyle in patients with a variety of disorders. A 9-item questionnaire with questions related to how fatigue interferes with certain activities and rates its severity. The Fatigue Severity Scale scores range from 9 to 63, with higher scores indicating a greater fatigue severity.)

  9. Incidence of rhabdomyolysis [ Time Frame: Baseline to Visit 4(up to 90 days) ]
    Incidence of rhabdomyolysis

  10. Incidence of serious liver dysfunction [ Time Frame: Baseline to Visit 4(up to 90 days) ]
    Incidence of serious liver dysfunction (AST or ALT increase more than three times from baseline)


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with recent ischemic stroke who meet both 1) and 2) criteria below. 1) Patients with acute ischemic stroke confirmed by DWI(diffusion-weighted imaging)

    This is satisfied by meeting at least one of the following two criteria:

    1. Patients who sustained stroke symptoms for more than 24 hours and had acute ischemic lesions on DWI.
    2. Patients with acute ischemic lesions in DWI who had improved symptoms within 24 hours.

      2) Patients with ischemic stroke within 90 days.

  2. Statin therapy indicated according to the recommendations of the 2014 American Heart Association/American Stroke Association guidelines.

    This is accomplished by meeting at least one of the following three criteria:

    1. Patients with ischemic stroke due to arteriosclerosis and LDL-C ≥ 100 mg / dL. (Class I; Level of Evidence B)
    2. Patients with ischemic stroke due to arteriosclerosis and LDL-C <100 mg / dL. (Class I; Level of Evidence C)
    3. Patients who require statin therapy due to other associated atherosclerotic cardiovascular disease. (Class I; Level of Evidence A).
  3. Patients without statin dose within 28 days before ischemic stroke.
  4. Patients who measured baseline LDL-C levels after an ischemic stroke. This is satisfied by meeting at least one of the following two criteria:

    1. Patients who had a baseline LDL-C level before the onset of a recent ischemic stroke and started statin therapy.
    2. Patients hospitalized with acute ischemic stroke who had baseline LDL-C levels after initiation of statin therapy should meet both of the following conditions:

      1. Patients with LDL-C levels measured within 3 days after initiation of statin therapy
      2. Patients in whom randomization and administration of the study drug can be administered within 7 days after baseline LDL-C measurement.
  5. Adults over 19 years.
  6. Those who voluntarily agreed in writing to the trial.

Exclusion Criteria:

  1. Planned vascular intervention before the end of trial
  2. Significant hepatic dysfunction (Aspartate Aminotransferase or Alanine Aminotransferase >120 IU/L)
  3. Allergy or contraindication to rosuvastatin or ezetimibe
  4. Alcohol or drug addiction
  5. Pregnancy or breast-feeding
  6. Severe anemia: Hb level <10 g/dL for men and <9 g/dL for women
  7. Bleeding diathesis: platelet count <100,000/μl or prothrombin time International Normalized Ratio > 1·7
  8. Inability or unwillingness to comply with study-related procedures
  9. Employees of the investigator or study center, with direct involvement in the current study
  10. Women unwilling to continue contraception during the study period
  11. Participation in other clinical trials within three-month
  12. Malignancy or other serious medical conditions with a life expectancy <6 months
  13. Treatment with protease inhibitors or cyclosporine
  14. Patients with severe renal impairment (creatinine clearance <30 mL / min)
  15. Other reasons for ineligibility judged by investigators
Contacts and Locations

Contacts
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Contact: Keun-Sik Hong, MD., PhD. 82-31-910-7277 nrhks@paik.ac.kr

Locations
Layout table for location information
Korea, Republic of
Korea University Ansan Hospital Recruiting
Ansan-Si, Gyeonggi-Do, Korea, Republic of
Contact: Jin-Man Jung, MD., PhD.       sodium75@hanmail.net   
Hallym University Medical Center Recruiting
Anyang-si, Gyeonggi-Do, Korea, Republic of
Contact: Mi-Sun Oh, MD., PhD.       iyyar@hallym.ac.kr   
Myongji Hospital Recruiting
Goyang-Si, Gyeonggi-Do, Korea, Republic of
Contact: Jong-Ho Park, MD., PhD.       neurocraft.jhp@gmail.com   
Inje University Ilsan Paik Hospital Recruiting
Ilsan, Gyeonggi-Do, Korea, Republic of
Contact: Keun-Sik Hong, MD, Phd    82-31-910-7277    nrhks@paik.ac.kr   
Chung-Ang University Hopital Not yet recruiting
Seoul, Korea, Republic of
Contact: Kwang-Yeol Park, MD., PhD.       sbaram1@cau.ac.kr   
Ewha Womans University Seoul hospital Recruiting
Seoul, Korea, Republic of
Contact: Tae-Jin Song, MD., PhD.       knstar@hanmail.net   
Korea University Guro Hospital Recruiting
Seoul, Korea, Republic of
Contact: Chi-Kyung Kim, MD., PhD.       ckkim7@korea.ac.kr   
Kyung-Hee University Medical Center Recruiting
Seoul, Korea, Republic of
Contact: Sung-Hyuk Heo, MD., PhD.       shheo73@khu.ac.kr   
Samsung Medical Center, Sungkyunkwan University School of Medicine Recruiting
Seoul, Korea, Republic of
Contact: Oh-Young Bang, MD., PhD.       ohyoung.bang@samsung.com   
Seoul National University Hospital Not yet recruiting
Seoul, Korea, Republic of
Contact: Tae-Jung Kim, MD.,PhD.       ttae35@gmail.com   
Seoul St Mary's Hospital Recruiting
Seoul, Korea, Republic of
Contact: Ja-Seong Koo, MD., PhD.       carotidstroke@gmail.com   
Severance Hospital, Yonsei University Health System Recruiting
Seoul, Korea, Republic of
Contact: Hyo-Suk Nam, MD., PhD.       hsnam@yuhs.ac   
Sponsors and Collaborators
Keun-Sik Hong
Ewha Womans University
Severance Hospital
Korea University
Korea University Guro Hospital
Myongji Hospital
Seoul St. Mary's Hospital
Samsung Medical Center
Seoul National University Hospital
Chung-Ang University Hosptial, Chung-Ang University College of Medicine
Hallym University Medical Center
Kyunghee University Medical Center
Inje University
Investigators
Layout table for investigator information
Principal Investigator: Keun-Sik Hong, MD., PhD. Department of Neurology, Inje University Ilsan Paik Hospital
Tracking Information
First Submitted Date  ICMJE June 17, 2019
First Posted Date  ICMJE June 20, 2019
Last Update Posted Date February 12, 2020
Actual Study Start Date  ICMJE September 9, 2019
Estimated Primary Completion Date November 12, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 19, 2019)
The percentage of subjects with LDL-C decreased more than 50% at 90days (±14 days) compared to Baseline [ Time Frame: Baseline, Visit 4(Day 90) ]
The percentage of subjects with LDL-C decreased more than 50% at 90days (±14 days) compared to Baseline
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 19, 2019)
  • Percentage of subjects with LDL-C less than 70 mg/dL at 90 days(±14 days) [ Time Frame: Baseline, Visit 4(Day 90) ]
    Percentage of subjects with LDL-C less than 70 mg/dL at 90 days(±14 days)
  • The percentage of subjects with LDL-C decreased more than or less than 70 mg/dL at 90 days(±14 days) [ Time Frame: Baseline, Visit 4(Day 90) ]
    The percentage of subjects with LDL-C decreased more than or less than 70 mg/dL at 90 days(±14 days)
  • The decrement of LDL-C at 90 days (±14 days) compared to baseline LDL-C (absolute difference and change) [ Time Frame: Baseline, Visit 4(Day 90) ]
    The decrement of LDL-C at 90 days (±14 days) compared to baseline LDL-C (absolute difference and change)
  • The percentage of subjects achieved multiple lipid level (Total-C < 200mg/dL, LDL-C < 70mg/dL and triglyceride < 150mg /dL) [ Time Frame: Baseline, Visit 4(Day 90) ]
    The percentage of subjects achieved multiple lipid level (Total-C < 200mg/dL, LDL-C < 70mg/dL and triglyceride < 150mg /dL)
  • Cardiovascular event rates including stroke (ischemic or hemorrhagic), coronary artery(myocardial infarction or coronary vascular reperfusion) and death related to vascular disease. [ Time Frame: Baseline to Visit 4(up to 90 days) ]
    Cardiovascular event rates including stroke (ischemic of hemorrhagic), coronary artery(myocardial infarction or coronary vascular reperfusion) and death related to vascular disease.
  • Number of Death of all causes. [ Time Frame: Baseline to Visit 4(up to 90 days) ]
    Number of Death of all causes.
  • Number of subjects with newly diagnosed diabetes. [ Time Frame: Visit 4(Day 90) ]
    Number of subjects with newly diagnosed diabetes.
  • Fatigue scale measured by Fatigue Severity Scale. [ Time Frame: Screening, Visit 4(Day 90) ]
    Fatigue scale measured by Fatigue Severity Scale. (The Fatigue Severity Scale is a 9-item scale which measures the severity of fatigue and its effect on a person's activity and lifestyle in patients with a variety of disorders. A 9-item questionnaire with questions related to how fatigue interferes with certain activities and rates its severity. The Fatigue Severity Scale scores range from 9 to 63, with higher scores indicating a greater fatigue severity.)
  • Incidence of rhabdomyolysis [ Time Frame: Baseline to Visit 4(up to 90 days) ]
    Incidence of rhabdomyolysis
  • Incidence of serious liver dysfunction [ Time Frame: Baseline to Visit 4(up to 90 days) ]
    Incidence of serious liver dysfunction (AST or ALT increase more than three times from baseline)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study on Rosuvastatin+Ezetimibe and Rosuvastatin for LDL-C Goal in Patients With Recent Ischemic Stroke
Official Title  ICMJE Moderate-intensity Rosuvastatin Plus Ezetimibe Versus High-intensity Rosuvastatin for Target LDL-C Goal Achievement in Patients With Recent Ischemic Stroke: a Randomized Clinical Trial
Brief Summary A randomized clinical trial for the comparison of the efficacy and safety of moderate-intensity rosuvastatin plus ezetimibe versus high-intensity rosuvastatin for target LDL-C goal achievement in patients with recent ischemic stroke
Detailed Description

The purpose of this study is to compare the efficiency and safety on the target LDL-C goal achievement between rosuvastatin 10 mg plus ezetimibe 10 mg (rosuvastatin/ezetimibe 10/10 mg) once daily versus rosuvastatin 20 mg once daily in patients with recent ischemic stroke.

The target LDL-C goal achievement rate in patients with recent ischemic stroke has not been well studied. In particular, no clinical studies have been conducted comparing the efficacy and safety of low-dose rosuvastatin plus ezetimibe with high-dose rosuvastatin single agent for achieving target LDL-C levels.

In this trial, the investigators aim to compare the efficacy of the target LDL-C achievement between rosuvastatin 10 mg plus ezetimibe 10 mg (rosuvastatin/ezetimibe 10/10 mg) and rosuvastatin 20 mg in patients with recent ischemic stroke.

For this trial, more than 292 patients (584 total) per group will be enrolled.

Subjects who were satisfied with the inclusion/exclusion criteria of this trial and who agreed to participate in the clinical trial in writing were randomly assigned to a 1:1 ratio in the experimental group (the low-dose combination of rosuvastatin plus ezetimibe) and comparator group (high-dose rosuvastatin).

The duration of administration of the drug for clinical trials is 90 days (±14 days), and the efficacy and safety evaluation parameters are compared with baseline.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Condition  ICMJE Stroke, Ischemic
Intervention  ICMJE
  • Drug: Experimental: Rosuvastatin/Ezetimibe 10
    • Rosuvastatin/Ezetimibe 10/10mg
    • orally administered once daily for 90 days
    Other Name: Rosuzet tab 10/10 mg
  • Drug: Active Comparator: Rosuvastatin 20mg
    • Rosuvastatin 20mg
    • orally administered once daily for 90 days
    Other Name: Suvast tab 20mg
Study Arms  ICMJE
  • Experimental: Rosuvastatin/Ezetimibe 10/10mg
    The experimental group is orally administered with rosuvastatin 10 mg plus ezetimibe 10 mg combination once daily for 90 days.
    Intervention: Drug: Experimental: Rosuvastatin/Ezetimibe 10
  • Active Comparator: Rosuvastatin 20mg
    The comparator group is orally administered with rosuvastatin 20 mg single agent once daily for 90 days
    Intervention: Drug: Active Comparator: Rosuvastatin 20mg
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 19, 2019)
584
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 12, 2020
Estimated Primary Completion Date November 12, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patients with recent ischemic stroke who meet both 1) and 2) criteria below. 1) Patients with acute ischemic stroke confirmed by DWI(diffusion-weighted imaging)

    This is satisfied by meeting at least one of the following two criteria:

    1. Patients who sustained stroke symptoms for more than 24 hours and had acute ischemic lesions on DWI.
    2. Patients with acute ischemic lesions in DWI who had improved symptoms within 24 hours.

      2) Patients with ischemic stroke within 90 days.

  2. Statin therapy indicated according to the recommendations of the 2014 American Heart Association/American Stroke Association guidelines.

    This is accomplished by meeting at least one of the following three criteria:

    1. Patients with ischemic stroke due to arteriosclerosis and LDL-C ≥ 100 mg / dL. (Class I; Level of Evidence B)
    2. Patients with ischemic stroke due to arteriosclerosis and LDL-C <100 mg / dL. (Class I; Level of Evidence C)
    3. Patients who require statin therapy due to other associated atherosclerotic cardiovascular disease. (Class I; Level of Evidence A).
  3. Patients without statin dose within 28 days before ischemic stroke.
  4. Patients who measured baseline LDL-C levels after an ischemic stroke. This is satisfied by meeting at least one of the following two criteria:

    1. Patients who had a baseline LDL-C level before the onset of a recent ischemic stroke and started statin therapy.
    2. Patients hospitalized with acute ischemic stroke who had baseline LDL-C levels after initiation of statin therapy should meet both of the following conditions:

      1. Patients with LDL-C levels measured within 3 days after initiation of statin therapy
      2. Patients in whom randomization and administration of the study drug can be administered within 7 days after baseline LDL-C measurement.
  5. Adults over 19 years.
  6. Those who voluntarily agreed in writing to the trial.

Exclusion Criteria:

  1. Planned vascular intervention before the end of trial
  2. Significant hepatic dysfunction (Aspartate Aminotransferase or Alanine Aminotransferase >120 IU/L)
  3. Allergy or contraindication to rosuvastatin or ezetimibe
  4. Alcohol or drug addiction
  5. Pregnancy or breast-feeding
  6. Severe anemia: Hb level <10 g/dL for men and <9 g/dL for women
  7. Bleeding diathesis: platelet count <100,000/μl or prothrombin time International Normalized Ratio > 1·7
  8. Inability or unwillingness to comply with study-related procedures
  9. Employees of the investigator or study center, with direct involvement in the current study
  10. Women unwilling to continue contraception during the study period
  11. Participation in other clinical trials within three-month
  12. Malignancy or other serious medical conditions with a life expectancy <6 months
  13. Treatment with protease inhibitors or cyclosporine
  14. Patients with severe renal impairment (creatinine clearance <30 mL / min)
  15. Other reasons for ineligibility judged by investigators
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 19 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Keun-Sik Hong, MD., PhD. 82-31-910-7277 nrhks@paik.ac.kr
Listed Location Countries  ICMJE Korea, Republic of
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03993236
Other Study ID Numbers  ICMJE ROSETTA-Stroke
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Keun-Sik Hong, Inje University
Study Sponsor  ICMJE Keun-Sik Hong
Collaborators  ICMJE
  • Ewha Womans University
  • Severance Hospital
  • Korea University
  • Korea University Guro Hospital
  • Myongji Hospital
  • Seoul St. Mary's Hospital
  • Samsung Medical Center
  • Seoul National University Hospital
  • Chung-Ang University Hosptial, Chung-Ang University College of Medicine
  • Hallym University Medical Center
  • Kyunghee University Medical Center
  • Inje University
Investigators  ICMJE
Principal Investigator: Keun-Sik Hong, MD., PhD. Department of Neurology, Inje University Ilsan Paik Hospital
PRS Account Inje University
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP