Stroke Trials Registry

PREVAIL
PREvention of VTE after Acute Ischemic Stroke with LMWH or Enoxaparin.

Principal Investigator
Luc Sagnard

PI Address
Luc Sagnard
Study Director
Sanofi-Aventis

Contact Address
Salah Mahyaoui
Sanofi-Aventis
Phone: 33-6-73-68-78-88

Sponsor

Trial Phase:	Phase IV
Study Size Actual:	1762
Centers Actual:	15
Max Time from onset:	48 Hours
Min Age:	18
Follow-up Duration:	90 Days
ISRCTN#	NCT00077805

Status:
Completed. Results were presented December 2006 at the 48th American Society of Hematology (ASH) annual meeting and published in 2007.

Purpose:
To demonstrate superiority of enoxaparin compared to unfractionated heparin (UFH) in the prevention of Venous Thromboembolism (VTE) following acute ischemic stroke.

Interventions:

Enoxaparin
Low-molecular-weight heparin.

Heparin (acute stroke)
Intravenous anticoagulant.

Location(s):
New Jersey, Australia, Austria, Brazil, Canada, Colombia, Czech Replublic, India, Israel, Italy, Korea, Mexico, Poland, South Africa, and Turkey.

Year Started: 2003

Year Finished: 2006

Year Presented: 2006

Year Published: 2007

Design:
Prevention, randomized, open label, active control, parallel assignment, and safety/efficacy study.

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.

Patient Involvement:
Patients were randomized to receive enoxaparin daily 40 mg SC or UFH 5000 IU SC Q 12 treatment for 10 days +/- 4 days with a follow up period of 90 days and stratified by NIH Stroke Scale Score (severe greater than or equal to 14 and less severe <14).

Primary Outcome:
Composite of symptomatic or asymptomatic deep-vein thrombosis (DVT), and/or symptomatic or fatal pulmonary embolism (PE) during the treatment period. Primary safety endpoints were symptomatic intracranial bleeding, major extracranial bleeding and all-cause mortality.

Secondary Outcome:
Incidence of VTE, incidence of stroke recurrence, rate of stroke progression, patient functional status, safety of using enoxaparin compared to UFH.

Results:
There were fewer composite endpoints (DVT, PE) in patients treated with enoxaparin than with unfractionated heparin (UFH) during the 90-day treatment period (10.2% vs 18.1%; p=.0001; relative risk reduction 43%). Proximal DVT was also reduced (4.5% vs 9.6%; p=.0003; relative risk reduction 53%). Clinically important bleeding was not significantly different between enoxaparin and UFH (1.3% vs 0.7%, p=.20).

Source of Information:
ClinicalTrials.gov.
Lancet 2007; 369: 1347–55.

Web Links and Publications:

The efficacy and safety of enoxaparin versus unfractionated heparin for the prevention of venous thromboembolism after acute ischaemic stroke (PREVAIL Study): an open-label randomised comparison.
Lancet 2007 Apr 21;369(9570):1347-55

ClinicalTrials.gov
http://clinicaltrials.gov/ct2/show/NCT00077805?term=NCT00077805&rank=1

This information last updated on: 5/2/2007

Reviewed on: 08/27/2008.

UID: 717