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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Acute Ischemic Stroke

Intervention / Treatment
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* Drug: Enoxaparin sodium


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Enoxaparin sodium|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative occurrence of VTE events (deep-vein thrombosis, pulmonary embolism) |  | 10 ± 4 days following acute ischemic stroke | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cumulative VTE events |  | at 30-day, 60-day and 90-day | 
| stroke recurrence, stroke progression, National Institute of Health Stroke Scale (NIHSS) scores |  | during treatment and follow-up periods | 
| Modified Rankin Scale (MRS) scores |  | at 30-day and 90-day follow-up | 
| major & minor hemorrhages |  | from the inform consent signed up to the end of the study | 
| Treatment emergent adverse events (TEAE), serious adverse events (SAE), all-cause mortality |  | from the inform consent signed up to the end of the study |