Enoxaparin and/or Minocycline in Acute Stroke
Information source: New York University School of Medicine
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Acute Ischemic Stroke
Intervention: Enoxaparin (Drug); Minocycline (Drug)
Phase: N/A
Status: Terminated
Sponsored by: New York University School of Medicine Official(s) and/or principal investigator(s): Saran Jonas, M.D., Principal Investigator, Affiliation: Department of Neurology; New York University School of Medicine Giacinto Grieco, M.D., Study Director, Affiliation: Department of Neurology; New York University School of Medicine
Summary
The purpose of this study is to investigate whether enoxaparin, minocycline, or both
medications in combination may help in recovery from acute stroke.
Enoxaparin (brand name Lovenox®) is a medication approved for use in humans to prevent and
to treat blood clots in deep veins in certain specific medical situations. Minocycline
(brand name Minocin®) is a tetracycline antibiotic approved to treat a number of bacterial
infections in humans. The investigators are studying these medications in acute human
stroke because they have each been separately shown to reduce the amount of injured brain
tissue in rats made to have acute ischemic stroke experimentally. In a human trial
comparing minocycline with placebo (a sugar pill) acute ischemic stroke patients who took
minocycline had better recovery after 1 week, 1 month and 3 months than patients who took
placebo.
Clinical Details
Official title: Pilot Study of Treatment With Intravenous Enoxaparin and/or Oral Minocycline to Limit Infarct Size After Ischemic Stroke
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Indices of salvaged ischemic penumbra and of final infarct volume based on quantitative volumetric analyses of pre- and post-treatment perfusion-weighted and diffusion-weighted brain MR imaging
Secondary outcome: NIH Stroke Scale scoresModified Rankin Scale score
Detailed description:
Enoxaparin is a low molecular weight heparin (average molecular weight 4,500 daltons, vs.
12,000 to 15,000 daltons for unfractionated heparin) administered subcutaneously and
intravenously. It is a marketed drug FDA-approved in various clinical situations for: the
prevention and treatment of deep vein thrombosis; and in the treatment of acute myocardial
infarction. Minocycline is an orally administered antibiotic of the tetracycline class. It
is a marketed drug FDA-approved for the treatment of various bacterial and rickettsial
infections. Both medications have been found to be neuroprotective in experimental stroke
models. Minocycline has shown promise in a human acute stroke study.
This study is designed to investigate two logistically simple treatment regimens, singly or
in combination, employing these medications for acute ischemic stroke:
1. pulsed intravenous (iv) administration of enoxaparin initiated within 6 hours and
completed by 24 hours after stroke onset; and
2. oral minocycline treatment once daily for five days.
The goal of treatment is neuroprotection: the limitation of the loss of brain tissue that
follows ischemic stroke.
Eligibility
Minimum age: 18 Years.
Maximum age: 95 Years.
Gender(s): Both.
Criteria:
There are two Study Sections: A and B
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Study Section A Inclusion Criteria:
1. acute ischemic stroke in an adult in-patient who can complete screening and begin
study treatment within 6 hours of stroke onset (onset time defined as the last time
the patient was known to be at his/her usual level of functioning)
2. patient not a candidate for rTPA treatment because treatment cannot be started within
the required 3 hours after stroke onset, or because rTPA treatment is refused.
Study Section A Exclusion Criteria:
1. intracranial hemorrhage;
2. subfalcine, transtentorial, or foramen magnum herniation on CT or MRI scan of the
brain;
3. history of hypersensitivity or intolerance to or toxicity from enoxaparin, other
heparinoids, heparin, minocycline, or other tetracyclines;
4. weight 125lbs or less;
5. active bleeding;
6. thrombolytic treatment or major surgery in the previous 24 hours;
7. anticipated need for treatment with coumarin, or a low-molecular weight heparin other
than enoxaparin, or unfractionated heparin before 36 hours after stroke onset (but
see deep venous thrombosis prophylaxis, below);
8. INR above the normal range;
9. known coagulopathy;
10. platelet count <100,000/mm3 (if the count drops below 100,000 while on enoxaparin,
the medication will be stopped)
11. pregnancy or lactation;
12. undergoing dialysis; severe renal impairment (creatinine clearance known or estimated
to be <30ml/min);
13. mean arterial BP (taken to be 1/3 of the difference in mm Hg between diastolic BP and
systolic BP, added to the diastolic BP) of 130 mm Hg or greater; (if the mean
arterial BP is 130 mm Hg or greater but can be reduced by treatment to < 130 mm Hg,
with systolic BP in the 150 169 mm Hg range, the patient may be entered).
Patients in Study Section A will be randomly assigned to one of the four treatment arms:
enoxaparin, minocycline, enoxaparin and minocycline, or no intervention.
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Study Section B Inclusion Criteria:
1. acute ischemic stroke in an adult in-patient who can complete screening and begin
study treatment within 24 hours of stroke onset (onset time defined as the last time
the patient was known to be at his/her usual level of functioning;)
2. patient does not qualify for, or declines to participate in, Study Section A.
Study Section B Exclusion Criteria:
1. acute primary intracranial hemorrhage;
2. subfalcine, transtentorial, or foramen magnum herniation on CT or MRI scan of the
brain;
3. pregnancy or lactation.
Patients in Study Section B will be randomly assigned to one of TWO treatment arms:
minocycline, or no intervention.
Locations and Contacts
Bellevue Hospital Center, New York, New York 10016, United States
New York University Langone Medical Center, New York, New York 10016, United States
Additional Information
Related publications: Lampl Y, Boaz M, Gilad R, Lorberboym M, Dabby R, Rapoport A, Anca-Hershkowitz M, Sadeh M. Minocycline treatment in acute stroke: an open-label, evaluator-blinded study. Neurology. 2007 Oct 2;69(14):1404-10. Mary V, Wahl F, Uzan A, Stutzmann JM. Enoxaparin in experimental stroke: neuroprotection and therapeutic window of opportunity. Stroke. 2001 Apr;32(4):993-9. Quartermain D, Li Y, Jonas S. Enoxaparin, a low molecular weight heparin decreases infarct size and improves sensorimotor function in a rat model of focal cerebral ischemia. Neurosci Lett. 2000 Jul 14;288(2):155-8. Quartermain D, Li YS, Jonas S. The low molecular weight heparin enoxaparin reduces infarct size in a rat model of temporary focal ischemia. Cerebrovasc Dis. 2003;16(4):346-55. Xu L, Fagan SC, Waller JL, Edwards D, Borlongan CV, Zheng J, Hill WD, Feuerstein G, Hess DC. Low dose intravenous minocycline is neuroprotective after middle cerebral artery occlusion-reperfusion in rats. BMC Neurol. 2004 Apr 26;4:7. Yrjänheikki J, Tikka T, Keinänen R, Goldsteins G, Chan PH, Koistinaho J. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13496-500. Liu Z, Fan Y, Won SJ, Neumann M, Hu D, Zhou L, Weinstein PR, Liu J. Chronic treatment with minocycline preserves adult new neurons and reduces functional impairment after focal cerebral ischemia. Stroke. 2007 Jan;38(1):146-52. Epub 2006 Nov 22.
Starting date: April 2009
Last updated: July 7, 2015
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