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.
Trial Stopped: Slow enrollment
- Rosuvastatin (Crestor)Drug
Intervention Desc: Rosuvastatin 20mg tablet, once daily, for 14 days ARM 1: Kind: Experimental Label: Rosuvastatin Description: Rosuvastatin 20mg tablet, once daily, for 14 days
- Placebo: Sugar pill Other
Other Names: Placebo : sugar pill Intervention Desc: Placebo tablet, once daily, for 14 days ARM 1: Kind: Experimental Label: Placebo
- Placebo tablet Drug
Intervention Desc: Placebo tablet, once daily, for 14 days ARM 1: Kind: Experimental Label: Placebo Description: Placebo tablet, once daily, for 14 days
- Allocation: Randomized
- Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
- Purpose: Treatment
- Endpoint: Efficacy Study
- Intervention: Parallel Assignment
|Type||Measure||Time Frame||Safety Issue|
|Primary||Presence Of Newly Developed DWI Or FLAIR Lesions||During 14 days of treatment||Yes|
|Secondary||Number Or Volume Of Newly Developed DWI Or FLAIR Lesions With Percent Improvement Of NIHSS Score||During 14 days of treatment||Yes|
|Primary||Presence Of Newly Developed DWI Lesions||During 14 days of treatment||Yes|
|Secondary||Volume Of DWI Lesions With Percent Improvement Of NIHSS Score||During 14 days of treatment||Yes|