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

Acute Ischemic Stroke Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00077805
• Other study ID #: XRP4563H_4001
• Status: Completed
• Phase: Phase 4
• First received: February 12, 2004
• Last updated: January 10, 2011
• Start date: August 2003

Study information

• Verified date: January 2011
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. primary completion date: July 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Acute Ischemic Stroke
• Ischemia
• Stroke
• Thromboembolism
• Venous Thromboembolism

Intervention

Drug:
• Enoxaparin sodium

Locations

Country	Name	City	State
Australia	Sanofi-Aventis	North Ryde
Austria	Sanofi-Aventis	Vienna
Brazil	Sanofi-Aventis	Sao Paulo
Canada	Sanofi-Aventis	Laval
Colombia	Sanofi-Aventis	Bogota
Czech Republic	Sanofi-Aventis	Prague
India	Sanofi-Aventis	Mumbai
Israel	Sanofi-Aventis	Natanya
Italy	Sanofi-Aventis	Milan
Korea, Republic of	Sanofi-Aventis	Seoul
Mexico	Sanofi-Aventis	Mexico
Poland	Sanofi-Aventis	Warsaw
South Africa	Sanofi-Aventis	Johannesburg
Turkey	Sanofi-Aventis	Istanbul
United States	Sanofi-Aventis	Bridgewater	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Brazil,  Canada,  Colombia,  Czech Republic,  India,  Israel,  Italy,  Korea, Republic of,  Mexico,  Poland,  South Africa,  Turkey, 

References & Publications (2)

Kase CS, Albers GW, Bladin C, Fieschi C, Gabbai AA, O'Riordan W, Pineo GF; PREVAIL Investigators. Neurological outcomes in patients with ischemic stroke receiving enoxaparin or heparin for venous thromboembolism prophylaxis: subanalysis of the Prevention — View Citation

Sherman DG, Albers GW, Bladin C, Fieschi C, Gabbai AA, Kase CS, O'Riordan W, Pineo GF; PREVAIL Investigators. The efficacy and safety of enoxaparin versus unfractionated heparin for the prevention of venous thromboembolism after acute ischaemic stroke (PR — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cumulative occurrence of VTE events (deep-vein thrombosis, pulmonary embolism)		10 ± 4 days following acute ischemic stroke	No
Secondary	cumulative VTE events		at 30-day, 60-day and 90-day	No
Secondary	stroke recurrence, stroke progression, National Institute of Health Stroke Scale (NIHSS) scores		during treatment and follow-up periods	No
Secondary	Modified Rankin Scale (MRS) scores		at 30-day and 90-day follow-up	No
Secondary	major & minor hemorrhages		from the inform consent signed up to the end of the study	No
Secondary	Treatment emergent adverse events (TEAE), serious adverse events (SAE), all-cause mortality		from the inform consent signed up to the end of the study	No