The purpose of this dose escalation study is to evaluate the use of lovastatin for the
treatment of acute ischemic stroke.
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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.
Elkind MS, Sacco RL, MacArthur RB, Fink DJ, Peerschke E, Andrews H, Neils G, Stillman J, Corporan T, Leifer D, Cheung K. The Neuroprotection with Statin Therapy for Acute Recovery Trial (NeuSTART): an adaptive design phase I dose-escalation study of high-dose lovastatin in acute ischemic stroke. Int J Stroke. 2008 Aug;3(3):210-8. doi: 10.1111/j.1747-4949.2008.00200.x.