Pharmacokinetics of Enoxaparin in Intensive Care Patients

Study Overview
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Brief Summary
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To evaluate the pharmacokinetics of the thromboprophylactic agent enoxaparin in critically ill patients by comparing plasma anti-factor Xa activity when enoxaparin is administered either as a continuous intravenous infusion or subcutaneous bolus once daily. To investigate possible ongoing coagulation by coagulation markers during antithrombotic therapy with standard doses of enoxaparin

Official Title
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Plasma Anti-FXa Concentration After Continuous Intravenous Infusion and Subcutaneous Dosing of Enoxaparin for Thromboprophylaxis in Critically Ill Patients

Conditions
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Venous Thromboembolism

Intervention / Treatment
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* Drug: Enoxaparin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body Mass Index between 18-30 kg/m2 Critically ill patients requiring intensive care and pharmacological thromboprophylaxis Expected to remain in the ICU for at least 72 h Written informed consent obtained from the patient or his/her legal representative. Exclusion Criteria: Other indications for anticoagulant therapy than thromboprophylaxis Intracranial haemorrhage or central neurosurgical operation within three months prior to the admission Disseminated intravascular coagulation (DIC) according to the international society on Thrombosis and Haemostasis criteria Known heparin induced thrombocytopenia (HIT), or hypersensitivity to enoxaparin or heparin Treatment with enoxaparin or any other low-molecular weight heparin (LMWH) or heparin within 24 hours prior to ICU admission. If patient has received thromboprophylactic dose of LMWH within 24-72 hours before ICU admission inclusion can be done if measured anti-factor Xa level is <0.1 IU/ml at the time of admission Any long-term anticoagulant medication, expect low-dose aspirin Major bleeding within the last week unless definitively treated Blood platelet count <50, P-thromboplastin time (TT) <40% , international normalized ratio (INR) >1.7 Glomerular filtration rate less than 50 ml/min/1.73 m2 estimated from serum creatinine by applying Cockcroft-Gault equation or chronic dialysis HIV, hepatitis B virus, or hepatitis C virus infection Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Subcutaneous Enoxaparin<br>Subcutaneous enoxaparin 40 mg every 24 hours for three days | Drug: Enoxaparin<br>* Drug class: Low-molecular weight heparin<br>* Other names: Klexane (sanofi-Aventis Oy, Finland);|
| Active Comparator: Intravenous Enoxaparin<br>40 mg enoxaparin daily as continuous intravenous infusion for three days (72 hours) | Drug: Enoxaparin<br>* Drug class: Low-molecular weight heparin<br>* Other names: Klexane (sanofi-Aventis Oy, Finland);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma anti-factor Xa level | Change in plasma anti-factor Xa levels between baseline and 72 hours | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Venous thromboembolism | If clinically suspected a compression ultrasound will be done | 90 days | 
| Incidence of Bleeding | Major and minor bleeding events will be reported | 90 days |