Pharmacokinetics of Enoxaparin in Intensive Care Patients

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

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

Study Overview

• Status: Completed
• Conditions: Venous Thromboembolism
• Intervention / Treatment: Drug: Enoxaparin

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 4

Contacts and Locations

Study Locations

• Finland
  • Pirkanmaa
    • Tampere, Pirkanmaa, Finland, 33521
      • Tampere University Hospital
  • Uusimaa
    • Helsinki, Uusimaa, Finland, 00029
      • Helsinki University Central Hospital, Meilahti

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Tampere University Hospital
• Collaborators: Helsinki University Central Hospital

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): June 30, 2016
• Study Completion (Actual): September 30, 2016

Study Registration Dates

• First Submitted: March 18, 2014
• First Submitted That Met QC Criteria: March 20, 2014
• First Posted (Estimate): March 24, 2014

Study Record Updates

• Last Update Posted (Actual): October 27, 2017
• Last Update Submitted That Met QC Criteria: October 26, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thromboembolism; Venous Thromboembolism; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Enoxaparin
• Other Study ID Numbers: 2012-004599-21