Neuroprotection With Statin Therapy for Acute Recovery Trial (Neu-START)

• Status: Completed
• Trial end date: 2008-05-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this dose escalation study is to evaluate the use of lovastatin for the treatment of acute ischemic stroke.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Columbia University
• Treatments: Dihydromevinolin; L 647318; Lovastatin

Criteria

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.