Enoxaparin and/or Minocycline in Acute Stroke

This study has been terminated.
(Too few acute stroke patients available to meet enrollment requirements.)
Sponsor:
Collaborator:
James N. Kirby Foundation
Information provided by:
New York University School of Medicine
ClinicalTrials.gov Identifier:
NCT00836355
First received: February 3, 2009
Last updated: April 12, 2011
Last verified: April 2011
  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: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
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:


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 ]

Enrollment: 6
Study Start Date: April 2009
Study Completion Date: January 2010
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Enoxaparin Drug: Enoxaparin
2 (or 3) intravenous doses, the first on study entry, the last 24 hours later
Other Name: Lovenox®
Experimental: Minocycline
Minocycline 200 mg orally once daily for 5 days
Drug: Minocycline
200 mg orally once daily for 5 days
Other Name: Minocin®
Experimental: Enoxaparin and minocycline Drug: Enoxaparin
2 (or 3) intravenous doses, the first on study entry, the last 24 hours later
Other Name: Lovenox®
Drug: Minocycline
200 mg orally once daily for 5 days
Other Name: Minocin®
No Intervention: Control

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

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

--------------------------------------------

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.

  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: 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:

Responsible Party: Saran Jonas, M.D., Department of Neurology - NYU School of Medicine
ClinicalTrials.gov Identifier: NCT00836355     History of Changes
Other Study ID Numbers: 08-131
Study First Received: February 3, 2009
Last Updated: April 12, 2011
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:
Ischemia
Stroke
Cerebral Infarction
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Brain Ischemia
Minocycline
Enoxaparin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Anticoagulants
Hematologic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on July 23, 2014