Acute Ischemic Stroke
Conditions
Keywords
stroke, magnetic resonance imaging, enoxaparin, minocycline, NIH stroke scale, modified Rankin scale, neuroprotection
Brief 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.
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.
Interventions
DRUGEnoxaparin
2 (or 3) intravenous doses, the first on study entry, the last 24 hours later
DRUGMinocycline
200 mg orally once daily for 5 days
Sponsors
James N. Kirby Foundation
NYU Langone Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 95 Years
Healthy volunteers
No
Inclusion criteria
There are two Study Sections: A and B \-------------------------------------------- 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 | Within approximately 7 days of stroke onset |
Secondary
| Measure | Time frame |
|---|---|
| NIH Stroke Scale Scores | Baseline and after approximately one week |
| Modified Rankin Scale Score | Baseline, and approximately one week and 3 months later |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Enoxaparin Enoxaparin: 2 (or 3) intravenous doses, the first on study entry, the last 24 hours later | 0 |
| Minocycline Minocycline 200 mg orally once daily for 5 days
Minocycline: 200 mg orally once daily for 5 days | 4 |
| Enoxaparin and Minocycline Enoxaparin: 2 (or 3) intravenous doses, the first on study entry, the last 24 hours later
Minocycline: 200 mg orally once daily for 5 days | 0 |
| Control | 2 |
| Total | 6 |
Baseline characteristics
| Characteristic | Minocycline | Control | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 participants | 0 participants | 0 participants |
| Age, Categorical >=65 years | 0 participants | 1 participants | 1 participants |
| Age, Categorical Between 18 and 65 years | 4 participants | 1 participants | 5 participants |
| Gender Female | 1 participants | 1 participants | 2 participants |
| Gender Male | 3 participants | 1 participants | 4 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 4 | 0 / 0 | 0 / 2 |
| serious Total, serious adverse events | 0 / 0 | 0 / 4 | 0 / 0 | 0 / 2 |
Outcome results
Primary
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
Population: Although all participants completed the study, none of them had the necessary MRIs performed to gather outcome measure data. The study was closed once it was determined that logistically, it was not possible to complete the study at that point in time.
Secondary
Modified Rankin Scale Score
Time frame: Baseline, and approximately one week and 3 months later
Population: This trial was terminated early because of logistical challenges in data collection. No outcome measures data was able to be collected.
Secondary
NIH Stroke Scale Scores
Time frame: Baseline and after approximately one week
Population: This trial was terminated early because of logistical challenges in data collection. No outcome measures data was able to be collected.