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

Stroke Clinical Trial

— EUREKA  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01364220
• Other study ID #: D3560L00087
• Status: Terminated
• Phase: Phase 3
• First received: May 26, 2011
• Last updated: November 19, 2014
• Start date: August 2010
• Est. completion date: April 2013

Study information

• Verified date: November 2014
• Source: Severance Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Ministry for Health and Welfare
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 318
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Recurrence
• Stroke

Intervention

Drug:
• Rosuvastatin
Rosuvastatin 20mg tablet, once daily, for 14 days

Other:
• Placebo tablet
Placebo tablet, once daily, for 14 days

Locations

Country	Name	City	State
Korea, Republic of	Department of Neurology, Hallym University Sacred Heart Hospital	Anyang
Korea, Republic of	Department of Neurology Colleage of Medicine Dong-A University	Busan
Korea, Republic of	Department of Neurology Pusan National University Hospital	Busan
Korea, Republic of	Department of Neurology, College of Medicine Inje University, Paik Hospital	Busan
Korea, Republic of	Department of Neurology, Fatima hospital	Changwon
Korea, Republic of	Department of Neurology, Samsung Changwon hospital	Changwon
Korea, Republic of	Department of Neurology, Dongsan Medical Center, Keimyung University School of Medicine	Daegu
Korea, Republic of	Department of Neurology, Yeungnam University School of Medicine	Daegu
Korea, Republic of	Department of Neurology Konyang University Hospital	Daejon
Korea, Republic of	Department of Neurology, Chonnam National University Hospital	GwangJu
Korea, Republic of	Department of Neurology, Chosun University Hospital	Gwangju
Korea, Republic of	Department of Neurology, Inha University Hospital	Incheon
Korea, Republic of	Department of Neurology, National health insurance corporation ilsan Hospital	Koyang-shi
Korea, Republic of	Department of Neurology Gangnam Severance Hospital	Seoul
Korea, Republic of	Department of Neurology Kyung Hee University East-West Neo Medical Center	Seoul
Korea, Republic of	Department of Neurology Seoul National University Hospital	Seoul
Korea, Republic of	Department of Neurology St. Mary's Hospital, Catholic University	Seoul
Korea, Republic of	Department of Neurology, Ewha Womans University Hospital	Seoul
Korea, Republic of	Department of Neurology, Hallym University Medical Center	Seoul
Korea, Republic of	Department of Neurology, Korean University Guro hospital	Seoul
Korea, Republic of	Department of Neurology, Kyung Hee University, College of Medicine	Seoul
Korea, Republic of	Department of Neurology, National Medical Center	Seoul
Korea, Republic of	Department of Neurology, Samsung Medical Center	Seoul
Korea, Republic of	Department of Neurology, Severance Hospital	Seoul
Korea, Republic of	Department of Neurology, University of Ulsan,Asan Medical Center	Seoul
Korea, Republic of	Department of Neurology,Sanggye Paik Hospital, Inje University College of Medicine	Seoul
Korea, Republic of	Department of Neurology, Wonju Christian Hospital	Wonju

Sponsors (2)

Lead Sponsor	Collaborator
Severance Hospital	AstraZeneca

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Presence Of Newly Developed DWI Lesions	The objective would be to Compare the recurrence rate of ischemic strike by comparing the PRESENCE of newly developed DWI between baseline and after 14 days of treatment.	During 14 days of treatment	Yes
Secondary	Volume Of DWI Lesions With Percent Improvement Of NIHSS Score	Percent Improvement Based On NIHSS Score Measurements At Baseline, 5 Days And 14 Days Of Treatment.; Volume Of DWI Lesions	During 14 days of treatment	Yes

External Links

•   an independent web resource for information of stroke care and research