Neuroprotection With Statin Therapy for Acute Recovery Trial Phase 2

Inclusion Criteria

• Age >18
• Satisfies the criteria for ischemic stroke: acute focal neurological deficit of likely ischemic vascular origin.
• Patient or legally authorized representative has provided written informed consent prior to study entry. Patient who regains capacity provides his/her written consent to remain in the study.
• Patient can receive the first treatment dose within 0-24 hours of stroke onset. For patients found with stroke on awakening, it will be assumed that the stroke occurred the last time that the patient was known to be normal.
• Patient has pretreatment brain CT scan compatible with ischemic stroke and excludes hemorrhagic and non-vascular etiologies of symptoms.
• Patients taking statins at time of stroke may be included.
• Patients receiving standard dose intravenous tPA or mechanical interventional procedures may be enrolled.

Exclusion Criteria

• Brain imaging study shows a lesion other than ischemic stroke that could explain patient's symptoms (intracranial or subarachnoid hemorrhage, arteriovenous malformation, aneurysm, multiple sclerosis, tumor, abscess or other). Asymptomatic meningiomas are allowed.
• Mild stroke, defined as NIH Stroke Scale 4 points on the first three items of the NIHSS).
• History of intolerance or allergic reaction to any statins (myotoxicity, hepatic dysfunction, rash, etc.)
• Use of drugs within past 30 days that utilize the cytochrome CYP3A pathway (cyclosporine, itraconazole, ketoconazole, erythromycin, clarithromycin, nefazodone, posaconazole, voriconazole, dronedarone, diltiazem, colchicine and ranolazine).
• Use of drugs within past 30 days that increase risk of myotoxicity with statins (gemfibrozil, other fibrates, niacin, amiodarone, verapamil).
• Baseline major electrolyte disturbances (sodium 150, potassium 5.5).
• Recent major trauma ( 2 X upper limit of normal.
• Unstable cardiovascular (includes uncontrolled hypertension), pulmonary, gastrointestinal, hepatic or musculoskeletal disease.
• Patient has evidence of severe congestive heart failure or has history of end-stage cardiovascular disease (e.g. CHF NYHA Class III or IV or unstable angina).
• Abnormal ECG showing: Hemodynamically significant arrhythmia or frequent PVCs (>5/minute) (controlled atrial arrhythmia will not be an exclusion); evidence of acute myocardial infarction; Mobitz Type II 2nd degree AV block or 3rd degree AV block; ventricular tachycardia or ventricular fibrillation.
• Significant renal insufficiency, indicated by serum creatinine >2.0 mg/dl.
• Hypoglycemia (glucose < 60 mg/dl) or diabetic ketoacidosis unresponsive to therapy.
• Any of these hematologic abnormalities: WBC <3.0 x 103/mm3; Platelet count <50,000/mm3
• Received an investigational drug within 30 days.
• Severe behavioral or social problems that may interfere with the conduct of clinical study procedures.
• Patient unlikely, in the investigator's opinion, to complete the study and return for follow-up visits for any reason.