Trial record 11 of 23 for:    Open Studies | "Jaundice"

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Columbia University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mitchell S Elkind, Columbia University
ClinicalTrials.gov Identifier:
NCT01976936
First received: October 30, 2013
Last updated: NA
Last verified: October 2013
History: No changes posted
  Purpose

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 Intervention Phase
Stroke
Rhabdomyolysis
Jaundice
Drug: Lovastatin
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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.

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Increase in Liver Function Tests (LFTs) [ Time Frame: 90 Days ] [ Designated as safety issue: Yes ]

    Primary safety outcome: the development of clinical or laboratory evidence of major hepatic toxicity 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.


  • Increase in Creatine Kinase (CK) [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]

    Secondary safety outcome: the development of clinical or laboratory evidence of rhabdomyolysis within 7 days of treatment onset.

    The secondary safety outcome will be defined as:

    An increase in CK 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:
  • Score on NIH Stroke Scale [ Time Frame: 90 days ] [ Designated as safety issue: No ]
    Measure of neurological outcomes.

  • Barthel Index Score [ Time Frame: 90 days ] [ Designated as safety issue: No ]
    Measure of functional outcomes.

  • Modified Rankin scores [ Time Frame: 90 days ] [ Designated as safety issue: No ]
    Measure of handicap.


Estimated Enrollment: 168
Study Start Date: February 2009
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: High Dose Lovastatin vs Low Dose Lovastatin
Previous Statin Use
Drug: Lovastatin
For patients already on statins, either standard dose lovastatin 80 mg daily for three days versus short-term, high-dose lovastatin 640 mg per day for 3 days.
Other Name: Mevacor
Active Comparator: High Dose Lovastatin vs Placebo
Statin Naive
Drug: Lovastatin
For patients already on statins, either standard dose lovastatin 80 mg daily for three days versus short-term, high-dose lovastatin 640 mg per day for 3 days.
Other Name: Mevacor
Other: Placebo
For patients who are not previous statin users: placebo for three days versus 640 mg of lovastatin for 3 days.
Other Name: microcrystalline cellulose

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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, azithromycin, clarithromycin, nefazodone).
  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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01976936

Contacts
Contact: Mitchell S Elkind, MD, MS 212 305-1710 mse13@columbia.edu
Contact: Tomoko Kitago, MD 212 305-0368 tk2229@cumc.columbia.edu

Locations
United States, California
University of California, Los Angeles Stroke Network Recruiting
Los Angeles, California, United States, 90024
Principal Investigator: Sidney Starkman, MD         
United States, Florida
University of Miami Miller School of Medicine Recruiting
Miami, Florida, United States, 33136
Principal Investigator: Jose Romano, MD         
United States, Massachusetts
Brigham & Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Principal Investigator: Steven K Feske, MD         
United States, New York
Mount Sinai School of Medicine Recruiting
New York, New York, United States, 10029
Principal Investigator: Mandip Dhamoon, MD, MPH         
Sponsors and Collaborators
Mitchell S Elkind
Investigators
Principal Investigator: Mitchell S Elkind, MD, MS Columbia University
  More Information

No publications provided

Responsible Party: Mitchell S Elkind, Associate Professor of Neurology and Epidemiology (in the Sergievsy Center), Columbia University
ClinicalTrials.gov Identifier: NCT01976936     History of Changes
Other Study ID Numbers: AAAD9004, 2P50NS049060
Study First Received: October 30, 2013
Last Updated: October 30, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Columbia University:
Stroke
Rhabdomyolysis
Jaundice

Additional relevant MeSH terms:
Jaundice
Rhabdomyolysis
Stroke
Cerebral Infarction
Hyperbilirubinemia
Pathologic Processes
Skin Manifestations
Signs and Symptoms
Muscular Diseases
Musculoskeletal Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Brain Ischemia
Lovastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 26, 2014