PREVAIL: PREvention of VTE After Acute Ischemic Stroke With LMWH Enoxaparin ( - VTE: Venous Thromboembolism - LMWH: Low Molecular Weight Heparin)

Primary objective:

* To demonstrate superiority of enoxaparin 40 mg sc qd in the prevention of VTE compared to UFH (unfractionated heparin) 5000 U sc q12 hours given for 10 ± 4 days following acute ischemic stroke.

Secondary objectives:

* To compare the incidence of VTE between the 2 treatment groups at 30, 60, and 90 days from the time of randomization
* To compare neurologic outcomes between the 2 treatment groups, including incidence of stroke recurrence, rate of stroke progression, and patient functional status, during the 10 ± 4 days of treatment, and after 30, 60, and 90 days from the time of randomization
* To evaluate the safety of using enoxaparin compared to UFH for VTE prevention in patients following acute ischemic stroke


Eligibility Criteria:
Inclusion criteria:

* Acute ischemic stroke, any territory, with an appropriate neuroradiologic study (head CT scan or brain MRI scan) providing results consistent with non hemorrhagic stroke
* Onset of symptoms of qualifying stroke within 48 hours prior to randomization. In patients receiving thrombolytic therapy for the acute stroke, such as tissue-type plasminogen activator (tPA), administration of study drug may not start until at least 24 hours after completion of thrombolytic therapy
* Significant motor impairment of the leg, as indicated by a NIHSS score ≥2 on item 6
* Inability to walk without assistance

Exclusion criteria:

* Females who are pregnant, breast-feeding, or of childbearing potential and not using medically acceptable and effective contraception
* Clinical evidence of VTE at screening
* Any evidence of active bleeding on the basis of clinical judgment
* Prior history of intracranial hemorrhage (including that at screening)
* Spinal or epidural analgesia or lumbar puncture within the preceding 24 hours
* Thrombolytic therapy (e.g., tPA) or intra-arterial thrombolytic therapy within the preceding 24 hours.Thrombolytic therapy is permitted for treatment of the acute stroke but must have been completed 24 hours prior to randomization.
* Comatose at screening (NIHSS score ≥2 on item 1a)
* Known or suspected cerebral aneurysm or arteriovenous malformation
* Confirmed malignancy that may pose an increased risk for bleeding or otherwise compromise follow-up or outcome assessment (e.g., lung cancer)
* Impaired hemostasis, i.e., known or suspected coagulopathy (acquired or inherited); baseline platelet count \<100,000/mm3; aPTT 1.5 X the laboratory upper limit of normal; or international normalized ratio(INR) \>1.5
* Major surgery or recent major trauma within the previous 3 months
* Anticipated need for full-dose treatment with therapeutic levels of an anticoagulant (LMWH, UFH, oral anticoagulant), e.g., for cardiogenic source of embolism or dissection
* Treatment with a LMWH or UFH at prophylactic dose for more than 48 hours prior to randomization(patients receiving LMWH or UFH less than 48 hours prior to randomization may be randomized)
* Allergy to heparin or enoxaparin sodium, or known hypersensitivity to heparin, enoxaparin, or pork products
* History of heparin or enoxaparin induced thrombocytopenia and/or thrombosis (heparin-induced thrombocytopenia \[HIT\], heparin-associated thrombocytopenia \[HAT\], or heparin-induced thrombotic thrombocytopenia syndrome \[HITTS\])
* History of hypersensitivity to iodinated contrast media and/or iodine
* Bacterial endocarditis
* Prosthetic heart valve
* Known or suspected severe anemia (Hg \<10.0 g/dL)
* Uncontrolled arterial hypertension (systolic blood pressure \[BP\] \>180 mmHg or diastolic BP \>100 mmHg) at the time of randomization or clinical hypertensive urgency
* Any other clinically relevant serious diseases, including severe liver disease or renal failure \[creatinine clearance \<30 mL/min on at least two occasions\].
* Treatment with other investigational agents or devices within the previous 30 days, planned use of other investigational drugs or devices, or previous enrollment in this study.