StrokePhase 2NeuSTART2NCT01976936
Neuroprotection With Statin Therapy for Acute Recovery Trial Phase 2
A Phase 2 study testing Low Dose Lovastatin and High Dose Lovastatin in people with Stroke and Rhabdomyolysis, run by Columbia University at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stroke, Rhabdomyolysis, Jaundice
- What is being tested?
- Low Dose Lovastatin and High Dose Lovastatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 162 participants
- Where
- 7 sitesUnited States
- Study dates
- Feb 2009to 30 Nov 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 who regains capacity provides his/her written consent to remain in the study.
- 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.
- Patients receiving standard dose intravenous tPA or mechanical interventional procedures may be enrolled.
Who cannot join
- 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.
- Mild stroke, defined as NIH Stroke Scale <2.
- Weight < 50 kg.
- 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, clarithromycin, nefazodone, posaconazole, voriconazole, dronedarone, diltiazem, colchicine and ranolazine).
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- 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 < 96F).
- 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) > 2 X upper limit of normal.
- Unstable cardiovascular (includes uncontrolled hypertension), pulmonary, gastrointestinal, hepatic or musculoskeletal disease.
- 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).
- 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) or diabetic ketoacidosis unresponsive to therapy.
- Any of these hematologic abnormalities: 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.
- Patient unlikely, in the investigator's opinion, to complete the study and return for follow-up visits for any reason.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Emory University
Atlanta, Georgia, 30322
Brigham & Women's Hospital
Boston, Massachusetts, 02115
University of California, Los Angeles Stroke Network
Los Angeles, California, 90024
Jackson Memorial Hospital
Miami, Florida, 33136
University of Miami Miller School of Medicine
Miami, Florida, 33136
Mount Sinai School of Medicine
New York, New York, 10029
The Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
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.
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.
Read the 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.
- Conditions
- Stroke, Rhabdomyolysis, Jaundice
- Being tested
- Low Dose Lovastatin, Placebo, High Dose Lovastatin
- Keywords
- Stroke, Rhabdomyolysis, Jaundice
- Medical subject headings
- Stroke, Rhabdomyolysis, Jaundice
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low Dose LovastatinDrug
Also called Mevacor
80 mg daily for 3 days
PlaceboOther
Also called microcrystalline cellulose
Placebo for 3 days
High Dose LovastatinDrug
Also called Mevacor
640 mg daily for 3 days
| Study group | Role | What they receive |
|---|---|---|
| High Dose Lovastatin | Experimental | High dose lovastatin (640 mg daily for three days) will be administered orally Receives: Drug: High Dose Lovastatin |
| Low Dose Lovastatin | Active comparator | Lovastatin 80 mg daily for three days will be administered orally to patients who were taking statin therapy at the time of enrolment Receives: Drug: Low Dose Lovastatin |
| Placebo | Placebo comparator | Placebo will be administered orally to patients who were NOT taking statin therapy at the time of enrolment Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 7 Days
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2013 (estimated)
- Study startFeb 2009
- Primary completion30 Nov 2015
- Study completion30 Nov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 162 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mitchell S Elkind, MD, MS, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01976936
- Sponsor's protocol ID
- AAAD9004
- Other IDs
- 2P50NS049060
- Acronym
- NeuSTART2
- Status last verified
- Nov 2025
- First submitted
- 30 Oct 2013
- Last updated
- 1 Dec 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 1 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01976936
- Acronym / sponsor ID
- NeuSTART2 / AAAD9004
- Conditions
- Stroke, Rhabdomyolysis, Jaundice
- Keywords
- Stroke, Rhabdomyolysis, Jaundice
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 162 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Feb 2009 (actual)
- Primary completion
- 30 Nov 2015 (actual)
- Study completion
- 30 Nov 2015 (actual)
- First posted
- 6 Nov 2013 (estimated)
- Results
- Posted 1 Dec 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| High Dose Lovastatin | Experimental | Drug: High Dose LovastatinHigh dose lovastatin (640 mg daily for three days) will be administered orally |
| Low Dose Lovastatin | Active comparator | Drug: Low Dose LovastatinLovastatin 80 mg daily for three days will be administered orally to patients who were taking statin therapy at the time of enrolment |
| Placebo | Placebo comparator | Other: PlaceboPlacebo will be administered orally to patients who were NOT taking statin therapy at the time of enrolment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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 who regains capacity provides his/her written consent to remain in the study.
- 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.
Key exclusion criteria (28 listed)
- 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.
- Mild stroke, defined as NIH Stroke Scale <2.
- Weight < 50 kg.
- 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.)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low Dose LovastatinAlso: Mevacor80 mg daily for 3 days | Drug | Low Dose Lovastatin |
| PlaceboAlso: microcrystalline cellulosePlacebo for 3 days | Other | Placebo |
| High Dose LovastatinAlso: Mevacor640 mg daily for 3 days | Drug | High Dose Lovastatin |
Primary outcome
Total Number of Participants With an Increase in Liver Function Tests (LFTs)
Time frame: 7 Days
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.
3 secondary outcomes
Mean Score on NIH Stroke Scale (NIHSS)
Time frame: 90 days
Total Number of Participants With a Barthel Index Score > 95
Time frame: 90 days
Total Number of Participants With a Modified Rankin Score of 0-1
Time frame: 90 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Dec 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mitchell S Elkind, MD, MS principal investigator
Columbia University
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Low Dose Lovastatin and High Dose Lovastatin in people with Stroke and Rhabdomyolysis, run by Columbia University at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total Number of Participants With an Increase in Liver Function Tests (LFTs) (time frame: 7 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Dec 2025.