Neuroprotection With Statin Therapy for Acute Recovery Trial Phase 2

NCT01976936 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: AAAD90042P50NS049060
• Study Type: interventional
• Target: 162
• Locations: 1 country
• Sites: 7

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.

Conditions

Stroke; Rhabdomyolysis; Jaundice

Keywords

Stroke; Rhabdomyolysis; Jaundice

Outcome Measures

Primary Outcomes (1)

• 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.

  7 Days

Secondary Outcomes (3)

• Mean Score on NIH Stroke Scale (NIHSS)

  90 days

• Total Number of Participants With a Barthel Index Score > 95

  90 days

• Total Number of Participants With a Modified Rankin Score of 0-1

  90 days

Study Arms (3)

High Dose Lovastatin

EXPERIMENTAL

High dose lovastatin (640 mg daily for three days) will be administered orally

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

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

Other: Placebo

Interventions

Low Dose Lovastatin DRUG

80 mg daily for 3 days

Also known as: Mevacor

Low Dose Lovastatin

Placebo OTHER

Placebo for 3 days

Also known as: microcrystalline cellulose

Placebo

High Dose Lovastatin DRUG

640 mg daily for 3 days

Also known as: Mevacor

High Dose Lovastatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Columbia University: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (7)

University of California, Los Angeles Stroke Network

Los Angeles, California, 90024, United States

Location

Jackson Memorial Hospital

Miami, Florida, 33136, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

The Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Stroke; Rhabdomyolysis; Jaundice

Interventions

Lovastatin; microcrystalline cellulose

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Muscular Diseases; Musculoskeletal Diseases; Hyperbilirubinemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Mitchell S.V. Elkind, MD, MS, MPhil
• Organization: Columbia University

mse13@cumc.columbia.edu

212-305-1710

Study Officials

• Mitchell S Elkind, MD, MS

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2013
• First Posted: November 6, 2013
• Study Start: February 1, 2009
• Primary Completion: November 30, 2015
• Study Completion: November 30, 2015
• Last Updated: December 1, 2025
• Results First Posted: December 1, 2025

Record last verified: 2025-11

Locations

US (7)