The Effects of Very Early Use of Rosuvastatin in Preventing Recurrence of Ischemic Stroke (EUREKA)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2010 by Severance Hospital.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
AstraZeneca
Information provided by:
Severance Hospital
ClinicalTrials.gov Identifier:
NCT01364220
First received: May 26, 2011
Last updated: July 20, 2011
Last verified: February 2010
  Purpose

It is anticipated that 548 subjects will be recruited from approximately 27 centres in South Korea.

This is an investigator-sponsored, double-blind, placebo-controlled, randomized, multi-centre study to assess the effects of rosuvastatin 20 mg compared to placebo in acute ischemic stroke patients, with the first dose within 18 hours after baseline MRI and continued treatment for 14 days.

Subjects will be male or female, over 20 years, with diagnosis of acute ischemic stroke with baseline MRI, and who are either statin-naïve or untreated with statin for the previous 3 months.

The objective would be to compare the recurrence rate of ischemic stroke by comparing the imaging parameters during 14 days of treatment and clinical improvement as defined by percent improvement based on NIHSS scores measurements at baseline, 5 days and 14 days of treatment.


Condition Intervention Phase
Stroke
Drug: Rosuvastatin
Other: Placebo: Sugar pill
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: An Investigator-Sponsored,Double Blind,Placebo-controlled,Randomised,Multi-centre Study to Assess the Effects of Very Early Use of Rosuvastatin in Preventing Recurrence of Ischemic Stroke

Resource links provided by NLM:


Further study details as provided by Severance Hospital:

Primary Outcome Measures:
  • Presence Of Newly Developed DWI Or FLAIR Lesions [ Time Frame: During 14 days of treatment ] [ Designated as safety issue: Yes ]
    The objective would be to Compare the recurrence rate of ischemic strike by comparing the PRESENCE of newly developed DWI or FLAIR imaging between baseline and after 14 days of treatment.


Secondary Outcome Measures:
  • Number Or Volume Of Newly Developed DWI Or FLAIR Lesions With Percent Improvement Of NIHSS Score [ Time Frame: During 14 days of treatment ] [ Designated as safety issue: Yes ]
    1. Percent Improvement Based On NIHSS Score Measurements At Baseline, 5 Days And 14 Days Of Treatment.
    2. Number Or Volume Of Newly Developed DWI Or FLAIR Lesions During 14 Days Of Treatment.


Estimated Enrollment: 548
Study Start Date: August 2010
Estimated Study Completion Date: August 2012
Estimated Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rosuvastatin
Rosuvastatin 20mg tablet, once daily, for 14 days
Drug: Rosuvastatin
Rosuvastatin 20mg tablet, once daily, for 14 days
Other Name: Crestor 20mg
Placebo Comparator: Placebo Other: Placebo: Sugar pill
Placebo tablet, once daily, for 14 days
Other Name: Placebo : sugar pill

Detailed Description:

Statins have action mechanisms that may work nicely in preventing recurrence during acute stage of infarction!

First, statins have antithrombotic effects and lower thrombogenicity. Statins prolong time to arterial thrombosis in endothelial injury model, inhibit P-selectin expression and platelet aggregation, reduce platelet PAR-1 thrombin receptor, and reduce tissue factor levels in plasma, its expression on monocyte surface, and atherosclerotic plaques. Second, statins enhance thrombolysis. They reduce PAI-1, increase t-PA activity and reduce fibrinogen level. Combined treatment of statins and t-PA in rats reduces the infarct size and downregulates expression of tissue factor, ICAM-1, vWF, and MMP-9. In addition, t-PA induced toxicity is reversed by statins.

Third, statins have anti-inflammatory actions that can stabilize and even regress plaques. Statins reduce the number of T-lymphocytes within plaques, inhibit migration and activation of monocyte/macrophage system, and reduce matrix metalloproteinase activity that play a critical role in plaque rupture. Rosuvastatin 40 mg could regress coronary atheroma burden at 2 years, and reduce progression of carotid intima-media thickness.

Benefits of statins in stroke patients are partially proven!

First, statins are well known to be effective in primary prevention of stroke. Second, statins were effective in secondary prevention of stroke. A high dose of statin (atorvastatin 80 mg) reduced recurrent stroke in patients with recent TIA or ischemic stroke when it was administrated 1-6 months after stroke onset. However, it is uncertain whether statins are effective during the first month after stroke. Third, outcomes are better in patients under statin treatment at the moment of stroke. Patients pretreated with statins showed better survival, less severe neurologic deficits, and improved outcomes when they were treated with thrombolysis.

However, it is unknown whether statin treatment in stroke patients is effective when it is administrated during the acute stage.

Based on strong supportive evidence in human and experimental animals which support theoretical superiority of rosuvastatin, this study will test a hypothesis that a high dose of rosuvastatin is effective in preventing recurrence during the first month after onset in ischemic stroke patients and should be given to all patients from their onset.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female over 20 years of age
  2. Ischemic stroke patients who were undertaken MRI within 48 hrs after onset of symptoms
  3. Patients underwent baseline MRI (DWI, FLAIR, GRE and MRA)
  4. Ischemic stroke patients with any degree of stenosis on the relevant artery of atherothrombotic origin appearing on DWI through MRA or CTA
  5. Statin-naïve (untreated with statin for the past 3 months)

Exclusion Criteria:

  1. Hemorrhagic stroke/ history of symptomatic hemorrhagic stroke.
  2. Presence of high-risk potential cardiac sources of embolism based on the TOAST classification or other determined etiology of stroke at the time of enrollment.
  3. Known major hematologic, neoplastic, metabolic, gastrointestinal or endocrine dysfunction which, in the judgment of the Investigator, may affect the subject's ability to complete the study.
  4. History of malignancy, except in subjects who have been disease-free >5 years or whose only malignancy has been basal or squamous cell skin carcinoma.
  5. Life-threatening illness indicating the subject is not expected to survive for at least 2 years.
  6. Secondary causes of nephrotic syndrome, and/or renal dysfunction (serum creatinine >2.0 mg/dL [177 mmol/L]) at screening.
  7. Significant medical or psychological condition that, in the opinion of the Investigator, would compromise the subject's safety or successful participation in the study.
  8. Unreliability as a study participant based on the Investigator's knowledge of the subject, such as drug or alcohol abuse.
  9. Pregnant or lactating women or women of childbearing potential who were not protected from pregnancy by an accepted method of contraception, such as the oral contraceptive pill, an intrauterine device or surgical sterilization
  10. Uncontrolled hypertension defined as either a resting diastolic blood pressure of >110 mmHg or a resting systolic blood pressure of >185 mmHg recorded at screening despite blood pressure lowering therapy.
  11. Clinically significant heart disease which, in the opinion of the Principal Investigator (or designee), is likely to require coronary bypass surgery, cardiac transplantation, surgical repair and/or replacement during the course of the study.
  12. Subjects who have symptoms consistent with moderate or greater severity of] congestive heart failure (CHF) (New York Heart Association [NYHA] Class III or IV), or whose most recent determination of left ventricular ejection fraction (LVEF) is <0.35.
  13. Triglyceride (TG) level of greater than 500 mg/dL at screening.
  14. LDL level of greater than 190 mg/dL at screening.
  15. Creatine kinase (CK) >3 times the upper limit of the normal (ULN) range at screening, because of the potential of statins to cause muscle abnormalities.
  16. Active liver disease or hepatic dysfunction, as determined by aspartate aminotransferase (AST [SGOT]), alanine aminotransferase (ALT [SGPT]) or bilirubin levels >3 x ULN at screening, because of the potential of statins to cause disturbances in liver function.
  17. Uncontrolled primary hypothyroidism (defined as thyroid stimulating hormone [TSH] >1.5 x ULN.
  18. Modified Rankin scale score 4 to 6 before stroke.
  19. Participation in any investigational clinical study for drug or device within 30 days prior to study entry or expectation to participate in any other investigational clinical study for drug or device during the course of this study.
  20. Patients who may need conventional angiography or intervention within 14 days after enrollment.
  21. Known serious hypersensitivity reactions to HMG-CoA reductase inhibitors.
  22. Use of any medication listed in the Prohibited Medications Section
  23. History of myopathy.
  24. Patients who has Galactose intolerance,lactose intolerance,Glucose- Galactose absorption problem.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01364220

Contacts
Contact: Hyo-Suk Nam, MD, PhD +82-2-2228-1617 hsnam@yuhs.ac
Contact: Myung-Jin Cha, MD, +82-2-2228-5284 MJCCHA@gmail.com

Locations
Korea, Republic of
Department of Neurology, Hallym University Sacred Heart Hospital Recruiting
Anyang, Korea, Republic of
Principal Investigator: Byung-Chul Lee, MD,PhD         
Department of Neurology, College of Medicine Inje University, Paik Hospital Recruiting
Busan, Korea, Republic of
Principal Investigator: Eung-Gyu Kim, MD, PhD         
Department of Neurology Colleage of Medicine Dong-A University Recruiting
Busan, Korea, Republic of
Principal Investigator: Jae-Kwan Cha, MD, PhD         
Department of Neurology Pusan National University Hospital Recruiting
Busan, Korea, Republic of
Principal Investigator: Han-Jin Cho, MD         
Department of Neurology, Samsung Changwon hospital Not yet recruiting
Changwon, Korea, Republic of
Principal Investigator: Myoung-Jin Cha, MD         
Department of Neurology, Fatima hospital Not yet recruiting
Changwon, Korea, Republic of
Principal Investigator: Yo-Han Jung, MD         
Department of Neurology, Dongsan Medical Center, Keimyung University School of Medicine Recruiting
Daegu, Korea, Republic of
Principal Investigator: Kyung-Hee Cho, MD         
Department of Neurology, Yeungnam University School of Medicine Recruiting
Daegu, Korea, Republic of
Principal Investigator: Min-Su Park, MD         
Department of Neurology Konyang University Hospital Recruiting
Daejon, Korea, Republic of
Principal Investigator: Ki-Wook Lee, MD         
Department of Neurology, Chonnam National University Hospital Recruiting
GwangJu, Korea, Republic of
Principal Investigator: Ki-Hyun Cho, MD, PhD         
Department of Neurology, Chosun University Hospital Recruiting
Gwangju, Korea, Republic of
Principal Investigator: Sung-Hwan Ahn, MD         
Department of Neurology, Inha University Hospital Recruiting
Incheon, Korea, Republic of
Principal Investigator: Joung-Ho Rha, MD, PhD         
Department of Neurology, National health insurance corporation ilsan Hospital Recruiting
Koyang-shi, Korea, Republic of
Principal Investigator: Jun-Hong Lee, MD, PhD         
Department of Neurology, Korean University Guro hospital Recruiting
Seoul, Korea, Republic of
Principal Investigator: Woo-Geun Seo, MD         
Department of Neurology, National Medical Center Recruiting
Seoul, Korea, Republic of
Principal Investigator: Jong-Yun Lee, MD         
Department of Neurology St. Mary's Hospital, Catholic University Recruiting
Seoul, Korea, Republic of
Principal Investigator: A-Hyun Cho, MD         
Department of Neurology, Ewha Womans University Hospital Recruiting
Seoul, Korea, Republic of
Principal Investigator: Yong-Jae Kim, MD, PhD         
Department of Neurology,Sanggye Paik Hospital, Inje University College of Medicine Recruiting
Seoul, Korea, Republic of
Principal Investigator: Sang-Won Han, MD         
Department of Neurology Gangnam Severance Hospital Recruiting
Seoul, Korea, Republic of
Principal Investigator: Kyung-Yul Lee, MD, PhD         
Department of Neurology, Severance Hospital Recruiting
Seoul, Korea, Republic of, 120-752
Principal Investigator: Ji-Hoe Heo, MD, PhD         
Sub-Investigator: Hyo-Suk Nam, MD, PhD         
Sub-Investigator: Young-Dae Kim, MD, PhD         
Sub-Investigator: Myung-Jin Cha, MD         
Department of Neurology, Kyung Hee University, College of Medicine Recruiting
Seoul, Korea, Republic of
Principal Investigator: Dae-Il Chang, MD, PhD         
Department of Neurology, Samsung Medical Center Recruiting
Seoul, Korea, Republic of
Principal Investigator: Gyeong-Moon Kim, MD, PhD         
Department of Neurology, Hallym University Medical Center Recruiting
Seoul, Korea, Republic of
Principal Investigator: Yang-ki Minn, MD,PhD         
Department of Neurology Kyung Hee University East-West Neo Medical Center Recruiting
Seoul, Korea, Republic of
Principal Investigator: Hye-Yeon Choi, MD         
Department of Neurology Seoul National University Hospital Recruiting
Seoul, Korea, Republic of
Principal Investigator: Byung-Woo Yoon, MD, PhD         
Department of Neurology, University of Ulsan,Asan Medical Center Recruiting
Seoul, Korea, Republic of
Principal Investigator: Jong-Sung Kim, MD, PhD         
Department of Neurology, Wonju Christian Hospital Recruiting
Wonju, Korea, Republic of
Principal Investigator: Seo-Hyun Kim, MD, PhD         
Sponsors and Collaborators
Severance Hospital
AstraZeneca
Investigators
Principal Investigator: Ji Hoe Heo, MD., Ph. D Department of Neurology, Severance Hospital, 250 Seongsan-no,Seodaemun-gu,Seoul,120-752, Korea
  More Information

Additional Information:
No publications provided

Responsible Party: Professor. Ji Hoe Heo, Department of Neurology, Yonsei University College of Medicine
ClinicalTrials.gov Identifier: NCT01364220     History of Changes
Other Study ID Numbers: D3560L00087
Study First Received: May 26, 2011
Last Updated: July 20, 2011
Health Authority: Korea: Ministry for Health, Welfare and Family Affairs

Keywords provided by Severance Hospital:
Additional relevant MeSH terms
Stroke
Cerebral Infarction
Cerebrovascular Disorders
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Magnetic Resonance Imaging
Recurrence

Additional relevant MeSH terms:
Stroke
Cerebral Infarction
Recurrence
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Brain Ischemia
Disease Attributes
Pathologic Processes
Rosuvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014