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