COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC:

Get the latest research information from NIH:
Working… Menu

Neuroprotection With Statin Therapy for Acute Recovery Trial Phase 2 (NeuSTART2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01976936
Recruitment Status : Completed
First Posted : November 6, 2013
Last Update Posted : July 24, 2017
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Mitchell S Elkind, Columbia University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Stroke Rhabdomyolysis Jaundice Drug: Low Dose Lovastatin Other: Placebo Drug: High Dose Lovastatin Phase 2

Detailed Description:

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 164 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2 Safety Study in Which Ischemic Stroke Patients Will be Randomized Within 24 Hours of Symptom Onset to Placebo or Oral Lovastatin 640 mg Per Day for 3 Days.
Actual Study Start Date : February 2009
Actual Primary Completion Date : January 2017
Actual Study Completion Date : January 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Lovastatin

Arm Intervention/treatment
Experimental: High Dose Lovastatin
High dose lovastatin (640 mg daily for three days) will be administered orally
Drug: High Dose Lovastatin
640 mg daily for 3 days
Other Name: Mevacor

Active Comparator: Low Dose Lovastatin
Lovastatin 80 mg daily for three days will be administered orally to patients who were taking statin therapy at the time of enrolment
Drug: Low Dose Lovastatin
80 mg daily for 3 days
Other Name: Mevacor

Placebo Comparator: Placebo
Placebo will be administered orally to patients who were NOT taking statin therapy at the time of enrolment
Other: Placebo
Placebo for 3 days
Other Name: microcrystalline cellulose

Primary Outcome Measures :
  1. Increase in Liver Function Tests (LFTs) [ Time Frame: 90 Days ]

    Primary safety outcome: 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;


    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.

Secondary Outcome Measures :
  1. Score on NIH Stroke Scale [ Time Frame: 90 days ]
    Measure of neurological outcomes.

  2. Barthel Index Score [ Time Frame: 90 days ]
    Measure of functional outcomes.

  3. Modified Rankin scores [ Time Frame: 90 days ]
    Measure of handicap.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Age >18
  2. Satisfies the criteria for ischemic stroke: acute focal neurological deficit of likely ischemic vascular origin.
  3. 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.
  4. 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.
  5. Patient has pretreatment brain CT scan compatible with ischemic stroke and excludes hemorrhagic and non-vascular etiologies of symptoms.
  6. Patients taking statins at time of stroke may be included.
  7. Patients receiving standard dose intravenous tPA or mechanical interventional procedures may be enrolled.

Exclusion Criteria:

  1. 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.
  2. Mild stroke, defined as NIH Stroke Scale <2.
  3. Weight < 50 kg.
  4. Patient is comatose, regardless of etiology (> 4 points on the first three items of the NIHSS).
  5. History of intolerance or allergic reaction to any statins (myotoxicity, hepatic dysfunction, rash, etc.)
  6. 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).
  7. Use of drugs within past 30 days that increase risk of myotoxicity with statins (gemfibrozil, other fibrates, niacin, amiodarone, verapamil).
  8. Baseline major electrolyte disturbances (sodium <125 or >150, potassium <3.0 or >5.5).
  9. Recent major trauma (<3 months).
  10. Hypothermia (body temperature < 96F).
  11. Baseline hypoxia (defined as oxygen saturation <92% on room air).
  12. History of likely or proven systemic viral infection within 30 days.
  13. Known HIV infection or use of protease inhibitors.
  14. Endocarditis likely as cause of stroke.
  15. Mitochondrial disorder likely as cause of stroke.
  16. Pregnancy or lactation.
  17. History of rhabdomyolysis, myopathy, or other severe muscle disease.
  18. History of hepatitis, decompensated liver disease (ascites, bleeding varices or encephalopathy), or liver failure.
  19. Liver function tests (ALT, AST) > 2 X upper limit of normal.
  20. Unstable cardiovascular (includes uncontrolled hypertension), pulmonary, gastrointestinal, hepatic or musculoskeletal disease.
  21. 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).
  22. 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.
  23. Significant renal insufficiency, indicated by serum creatinine >2.0 mg/dl.
  24. Hypoglycemia (glucose < 60 mg/dl) or diabetic ketoacidosis unresponsive to therapy.
  25. Any of these hematologic abnormalities: WBC <3.0 x 103/mm3; Platelet count <50,000/mm3
  26. Received an investigational drug within 30 days.
  27. Severe behavioral or social problems that may interfere with the conduct of clinical study procedures.
  28. Patient unlikely, in the investigator's opinion, to complete the study and return for follow-up visits for any reason.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01976936

Layout table for location information
United States, California
University of California, Los Angeles Stroke Network
Los Angeles, California, United States, 90024
United States, Florida
Jackson Memorial Hospital
Miami, Florida, United States, 33136
University of Miami Miller School of Medicine
Miami, Florida, United States, 33136
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Brigham & Women's Hospital
Boston, Massachusetts, United States, 02115
United States, New York
Mount Sinai School of Medicine
New York, New York, United States, 10029
United States, Pennsylvania
The Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Mitchell S Elkind
National Institute of Neurological Disorders and Stroke (NINDS)
Layout table for investigator information
Principal Investigator: Mitchell S Elkind, MD, MS Columbia University
Layout table for additonal information
Responsible Party: Mitchell S Elkind, Associate Professor of Neurology and Epidemiology (in the Sergievsy Center), Columbia University Identifier: NCT01976936    
Other Study ID Numbers: AAAD9004
2P50NS049060 ( U.S. NIH Grant/Contract )
First Posted: November 6, 2013    Key Record Dates
Last Update Posted: July 24, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Mitchell S Elkind, Columbia University:
Additional relevant MeSH terms:
Layout table for MeSH terms
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Skin Manifestations
Muscular Diseases
Musculoskeletal Diseases
L 647318
Anticholesteremic Agents
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors