Neuroprotection With Statin Therapy for Acute Recovery Trial (Neu-START)
Neuroprotection With Statin Therapy for Acute Recovery Trial (Neu-START)
The purpose of this dose escalation study is to evaluate the use of lovastatin for the
 treatment of acute ischemic stroke.
The Neuroprotection with Statin Therapy for Acute Recovery Trial (Neu-START) is part of the
 Specialized Program on Translational Research in Acute Stroke (SPOTRIAS). The overall goals
 of SPOTRIAS are to enhance delivery of acute stroke patient care with a focus on high-risk,
 disadvantaged populations, train acute stroke translational researchers, and conduct 3
 innovative acute stroke projects.

 Neu-START will enroll 33 patients with acute ischemic stroke presenting within 24 hours of
 onset. In the trial, investigators will treat the patients within 24 hours of symptom onset
 with short term high-dose lovastatin at escalating dosage. The escalating dosage levels will
 be 1, 3, 6, 8, and 10 mg/kg per day for 3 days. Lovastatin is in a class of drugs called
 statins, used for lowering cholesterol and preventing cardiovascular disease. Patients will
 be followed for 30 days for clinical and laboratory outcome events.

 The goals of this trial are to determine if lovastatin in increasing doses from 1 mg/kg to 10
 mg/kg daily for 3 days beginning 24 hours after acute ischemic stroke can be administered
 safely, and to assess the pharmacokinetics of lovastatin administered at high doses.
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 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.

 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.

 -  Patient had a stroke (ischemic or hemorrhagic) with residual deficit within 1 month
 prior to treatment.

 -  Mild stroke, defined as NIH Stroke Scale <2.

 -  Patient has received or is expected to receive intravenous rt-PA within 3 hours or
 intra-arterial rt-PA within 6 hours of stroke onset, according to our institutional
 standard of care.

 -  Receipt of intravenous rt-PA after 3 hours or intra-arterial rt-PA after 6 hours
 post-stroke onset.

 -  Seizure at presentation or within two weeks prior to stroke.

 -  Patient is comatose, regardless of etiology (> 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, azithromycin, clarithromycin,
 nefazodone).

 -  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 <125 or >150, potassium <3.0 or >5.5).

 -  Recent major trauma (<3 months).

 -  Hypothermia (body temperature < 96 degrees Fahrenheit).

 -  Baseline hypoxia (defined as oxygen saturation <92% on room air).

 -  History of likely or proven systemic viral infection within 30 days.

 -  Known HIV infection or use of protease inhibitors.

 -  Endocarditis likely as cause of stroke.

 -  Mitochondrial disorder likely as cause of stroke.

 -  Pregnancy or lactation.

 -  History of rhabdomyolysis, myopathy, or other severe muscle disease.

 -  History of hepatitis, decompensated liver disease (ascites, bleeding varices or
 encephalopathy), or liver failure.

 -  Liver function tests (ALT, AST) > 2X upper limit of normal.

 -  Unstable cardiovascular (includes uncontrolled hypertension), pulmonary,
 gastrointestinal, hepatic or musculoskeletal disease within one month (30 days) prior
 to treatment (by reported history).

 -  Patient has evidence of 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), significant hyperglycemia (glucose > 400 mg/dl) or
 diabetic ketoacidosis.

 -  Any of these hematologic abnormalities: Hb <10 g/dl; 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.