Enoxaparin and/or Minocycline in Acute Stroke

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.

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 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.