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

An Open-Label, Randomized, Parallel-Group, Multi-Center Study to Evaluate the Efficacy and Safety of Enoxaparin Versus Unfractionated Heparin in the Prevention of Venous Thromboembolism in Patients Following Acute Ischemic Stroke

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.