This trial will be a phase 2 randomized safety study in which ischemic stroke patients will be randomly assigned within 24 hours of symptom onset to placebo or standard dose lovastatin versus short-term high-dose lovastatin 640 mg per day for 3 days. The primary outcome of this Phase 2 study will be musculoskeletal and hepatic toxicity, defined by clinical and laboratory criteria, with a 3-month follow-up period (± 1 week). Secondary outcomes will include neurological outcome (National Institute of Health (NIH) Stroke Scale), functional outcomes (Barthel Index), and handicap (modified Rankin scores). Effects on inflammatory markers and lipid levels will also be assessed.
This is a phase 2 randomized, blinded and controlled safety study in patients with ischemic stroke. The time window for enrollment will be within 0-24 hours of symptom onset. For patients who are found with the stroke on awakening, it will be assumed that the stroke occurred the last time that the patient was known to be normal. All patients will be identified by the stroke acute care team in the emergency room of the participating centers, or in some cases, on the floor services of the hospital (i.e., for patients with stroke occurring in hospital). If preliminary data indicate that the patient meets eligibility criteria the patient (or legally authorized representative) will be approached about participation in the study, and consent obtained. Surrogate consent will be allowed at centers at which this is permitted according to regulations. Patients who are consented through a surrogate and subsequently regain capacity, will be approached and reconsented to continue in the study. The intervention chosen for this trial is either (1) placebo for patients not taking a statin at the time of admission OR lovastatin 80 mg in place of their regular statin for patients taking a statin (atorvastatin, simvastatin, rosuvastatin, pravastatin, fluvastatin, lovastatin) at time of enrolment VERSUS (2) oral lovastatin at dosage of 640 mg daily for 3 days. The time of first dose will be considered time 0. Patients will be administered the total daily dose in four daily divided doses (i.e., QID schedule). After the initial 3 days of acute dosage, all patients will receive statin therapy at the discretion of their treating physician.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
162
University of California, Los Angeles Stroke Network
Los Angeles, California, United States
Jackson Memorial Hospital
Miami, Florida, United States
University of Miami Miller School of Medicine
Miami, Florida, United States
Emory University
Atlanta, Georgia, United States
Brigham & Women's Hospital
Boston, Massachusetts, United States
Mount Sinai School of Medicine
New York, New York, United States
The Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
Total Number of Participants With an Increase in Liver Function Tests (LFTs)
The development of clinical or laboratory evidence of major hepatic toxicity within 7 days of treatment onset or the development of clinical or laboratory evidence of rhabdomyolysis within 7 days of treatment onset. The primary safety outcome will be defined as: Liver toxicity: LFT increase at any time point \> 3X upper limit of normal or development of jaundice, otherwise unexplained coagulopathy, or other clinical evidence of hepatitis or liver failure; or Muscle toxicity: An increase in CK (Creatine Kinase) at any time point \> 10 X upper limit of normal, or clinical evidence of muscle pain or weakness not related to the stroke and associated with CK \> 5 X upper limit of normal.
Time frame: 7 Days
Mean Score on NIH Stroke Scale (NIHSS)
The National Institutes of Health Stroke Scale (NIHSS) is a tool used by healthcare providers to objectively quantify the impairment caused by a stroke and to measure neurological outcomes. The NIHSS is composed of 11 items, with a score range of 0-42. Higher scores indicate greater impairment caused by a stroke.
Time frame: 90 days
Total Number of Participants With a Barthel Index Score > 95
The Barthel Index will be used to measure functional outcomes by counting the total number of individuals with a Barthel index score greater than or equal to 95. Numerical scores based on whether an individual requires physical assistance to perform the task or can complete it independently. An individual scoring 0 points would be dependent in all assessed activities of daily living, whereas a score of 100 would reflect independence in these activities, indicative of a better outcome.
Time frame: 90 days
Total Number of Participants With a Modified Rankin Score of 0-1
The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It will be used as a measure of handicap by looking at the total number of individuals with a score of 0-1. The scale runs from 0-6, running from perfect health without symptoms (score of 0) to death (score of 6). A score of 0 indicates a better outcome.
Time frame: 90 days
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