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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
318
Rosuvastatin 20mg tablet, once daily, for 14 days
Placebo tablet, once daily, for 14 days
Department of Neurology, Hallym University Sacred Heart Hospital
Anyang, South Korea
Department of Neurology Colleage of Medicine Dong-A University
Busan, South Korea
Department of Neurology Pusan National University Hospital
Busan, South Korea
Department of Neurology, College of Medicine Inje University, Paik Hospital
Busan, South Korea
Department of Neurology, Fatima hospital
Changwon, South Korea
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.
Time frame: During 14 days of treatment
Volume Of DWI Lesions With Percent Improvement Of NIHSS Score
1. Percent Improvement Based On NIHSS Score Measurements At Baseline, 5 Days And 14 Days Of Treatment. 2. Volume Of DWI Lesions
Time frame: During 14 days of treatment
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Department of Neurology, Samsung Changwon hospital
Changwon, South Korea
Department of Neurology, Dongsan Medical Center, Keimyung University School of Medicine
Daegu, South Korea
Department of Neurology, Yeungnam University School of Medicine
Daegu, South Korea
Department of Neurology Konyang University Hospital
Daejeon, South Korea
Department of Neurology, Chonnam National University Hospital
Gwangju, South Korea
...and 17 more locations