Clinical trial NCT00077805: PREVAIL: PREvention of VTE After Acute Ischemic Stroke With LMWH Enoxaparin ( - VTE: Venous Thromboembolism - LMWH: Low Molecular Weight Heparin)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute Ischemic Stroke
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2004-02-16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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


Eligibility criteria: 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.

Primary outcomes:
measure: Cumulative occurrence of VTE events (deep-vein thrombosis, pulmonary embolism)
timeFrame: 10 ± 4 days following acute ischemic stroke
Secondary outcomes:
measure: cumulative VTE events
timeFrame: at 30-day, 60-day and 90-day
measure: stroke recurrence, stroke progression, National Institute of Health Stroke Scale (NIHSS) scores
timeFrame: during treatment and follow-up periods
measure: Modified Rankin Scale (MRS) scores
timeFrame: at 30-day and 90-day follow-up
measure: major & minor hemorrhages
timeFrame: from the inform consent signed up to the end of the study
measure: Treatment emergent adverse events (TEAE), serious adverse events (SAE), all-cause mortality
timeFrame: from the inform consent signed up to the end of the study
Other outcomes:
Locations:
city: Bridgewater
country: United States
facility: Sanofi-Aventis
state: New Jersey
city: North Ryde
country: Australia
facility: Sanofi-Aventis
city: Vienna
country: Austria
facility: Sanofi-Aventis
city: Sao Paulo
country: Brazil
facility: Sanofi-Aventis
city: Laval
country: Canada
facility: Sanofi-Aventis
city: Bogota
country: Colombia
facility: Sanofi-Aventis
city: Prague
country: Czech Republic
facility: Sanofi-Aventis
city: Mumbai
country: India
facility: Sanofi-Aventis
city: Natanya
country: Israel
facility: Sanofi-Aventis
city: Milan
country: Italy
facility: Sanofi-Aventis
city: Seoul
country: Korea, Republic of
facility: Sanofi-Aventis
city: Mexico
country: Mexico
facility: Sanofi-Aventis
city: Warsaw
country: Poland
facility: Sanofi-Aventis
city: Johannesburg
country: South Africa
facility: Sanofi-Aventis
city: Istanbul
country: Turkey
facility: Sanofi-Aventis
Study officials:
affiliation: Sanofi
name: Luc Sagnard
role: STUDY_DIRECTOR
References:
citation: 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 of VTE after Acute Ischemic Stroke with LMWH (PREVAIL) study. Stroke. 2009 Nov;40(11):3532-40. doi: 10.1161/STROKEAHA.109.555003. Epub 2009 Aug 20.
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 (PREVAIL Study): an open-label randomised comparison. Lancet. 2007 Apr 21;369(9570):1347-1355. doi: 10.1016/S0140-6736(07)60633-3.