Enoxaparin and/or Minocycline in Acute Stroke - Full Text View

Sponsor:	New York University School of Medicine
Collaborator:	James N. Kirby Foundation
Information provided by:	New York University School of Medicine
ClinicalTrials.gov Identifier:	NCT00836355

Purpose

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.

Condition	Intervention
Acute Ischemic Stroke	Drug: Enoxaparin Drug: Minocycline

Study Type:	Interventional
Study Design:	Treatment, Randomized, Single Blind (Outcomes Assessor), Parallel Assignment, Efficacy Study
Official Title:	Pilot Study of Treatment With Intravenous Enoxaparin and/or Oral Minocycline to Limit Infarct Size After Ischemic Stroke

Resource links provided by NLM:

Drug Information available for: Minocycline Minocycline hydrochloride Enoxaparin Sodium

U.S. FDA Resources

Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:

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 [ Time Frame: Within approximately 7 days of stroke onset ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

NIH Stroke Scale scores [ Time Frame: Baseline and after approximately one week ] [ Designated as safety issue: No ]
Modified Rankin Scale score [ Time Frame: Baseline, and approximately one week and 3 months later ] [ Designated as safety issue: No ]

Estimated Enrollment:	64
Study Start Date:	April 2009
Estimated Study Completion Date:	September 2011
Estimated Primary Completion Date:	June 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Enoxaparin: Experimental	Drug: Enoxaparin 2 (or 3) intravenous doses, the first on study entry, the last 24 hours later
Minocycline: Experimental Minocycline 200 mg orally once daily for 5 days	Drug: Minocycline 200 mg orally once daily for 5 days
Enoxaparin and minocycline: Experimental	Drug: Enoxaparin 2 (or 3) intravenous doses, the first on study entry, the last 24 hours later Drug: Minocycline 200 mg orally once daily for 5 days
Control: No Intervention

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:

pulsed intravenous (iv) administration of enoxaparin initiated within 6 hours and completed by 24 hours after stroke onset; and
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

Ages Eligible for Study:	18 Years to 95 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

acute ischemic stroke in an adult patient who comes to the hospital in time to 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)
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;

Exclusion Criteria:

intracranial hemorrhage;
subfalcine, transtentorial, or foramen magnum herniation on CT or MRI scan of the brain;
history of hypersensitivity or intolerance to or toxicity from enoxaparin, other heparinoids, heparin, minocycline, or other tetracyclines;
weight 125lbs or less;
active bleeding;
thrombolytic treatment or major surgery in the previous 24 hours;
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);
INR above the normal range;
known coagulopathy;
platelet count <100,000/mm3 (if the count drops below 100,000 while on enoxaparin, the medication will be stopped)
pregnancy or lactation;
undergoing dialysis; severe renal impairment (creatinine clearance known or estimated to be <30ml/min);
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).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00836355

Locations

United States, New York
Bellevue Hospital Center
New York, New York, United States, 10016
New York University Langone Medical Center
New York, New York, United States, 10016

Sponsors and Collaborators

New York University School of Medicine

James N. Kirby Foundation

Investigators

Principal Investigator:	Saran Jonas, M.D.	Department of Neurology; New York University School of Medicine
Study Director:	Giacinto Grieco, M.D.	Department of Neurology; New York University School of Medicine

More Information

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.

Responsible Party:	Department of Neurology - NYU School of Medicine ( Saran Jonas, M.D. )
Study ID Numbers:	08-131
Study First Received:	February 3, 2009
Last Updated:	April 16, 2009
ClinicalTrials.gov Identifier:	NCT00836355 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by New York University School of Medicine:

stroke
magnetic resonance imaging
enoxaparin
minocycline

NIH stroke scale
modified Rankin scale
neuroprotection

Additional relevant MeSH terms:

Anti-Infective Agents
Minocycline
Anticoagulants
Molecular Mechanisms of Pharmacological Action
Cerebral Infarction
Hematologic Agents
Stroke
Nervous System Diseases
Vascular Diseases
Central Nervous System Diseases
Fibrinolytic Agents
Cardiovascular Agents

Ischemia
Brain Diseases
Cerebrovascular Disorders
Pharmacologic Actions
Enoxaparin
Anti-Bacterial Agents
Fibrin Modulating Agents
Pathologic Processes
Therapeutic Uses
Brain Ischemia
Cardiovascular Diseases
Brain Infarction

ClinicalTrials.gov processed this record on February 04, 2010