: Pharmacokinetics of Enoxaparin After Coronary Artery Bypass Graft Surgery

Study Overview
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Brief Summary
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To evaluate the pharmacokinetics of thromboprophylactic doses of LMWH enoxaparin in postoperative CABG patients, drug is administered either as a continuous intravenous infusion (CIV) or subcutaneous bolus (SCB) once per 72h. Plasma anti-Xa values are measured 12-14 times during study period and concentration maximums calculated to enable comparison of anti-Xa values between administration routes.

Detailed Description
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This is a prospective, randomized, controlled trial. After informed consent, 80 elective on pump CABG patients with a clinical indication for post-operative thromboprophylaxis will be studied in the Tampere University Heart Hospital. Study has two independent parts with 40 patients in both. Results are reported separately from these two parts of the study. Firts part of the study: After written consent, 20+20 patients are randomized to receive enoxaparin either as continuous intravenous infusion (treatment group) or subcutaneous bolus injection (control group). Enoxaparin dose is 40mg/24h either CIV of SCB. Anti-Xa values are measured 12-14 times from blood samples to evaluate the anticoagulation effect of enoxaparin. Second part of the study: After written consent, 20+20 patients are randomized to receive enoxaparin either as continuous intravenous infusion (treatment group) or subcutaneous bolus injection (control group). Enoxaparin dose is 1mg/kg/24h in CIV group and 0,5mg/kg twice a day in SCB group. In this second part of the study with eleveted enoxaparin dosage, 4 additional blood samples will be taken and analysed by ROTEM to investigate the overall coagulation status of the patients before and after the initiation of enoxaparin. The study will consist of two independent parts.

Official Title
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Anti-Xa Concentrations With Continuous Intravenous Infusion and Subcutaneous Administration of Enoxaparin After Coronary Artery Bypass Grafting: Randomized Clinical Trial

Conditions
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Venous Thromboembolism, Pulmonary Embolism, Thromboprophylaxis

Intervention / Treatment
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* Drug: Enoxaparin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI between 18-33 kg/m2 Elective on-pump CABG operation Indication for post-operative pharmacological thromboprophylaxis Written informed consent obtained from the patient or his/her legal representative. Exclusion Criteria: Other indications for anticoagulant therapy than thromboprophylaxis Known heparin induced thrombocytopenia (HIT), or hypersensitivity to enoxaparin or heparin Any long-term anticoagulant medication, expect low-dose aspirin Major bleeding within the last week unless definitively treated Blood platelet count <20, P-TT <20 % or INR >1.7 GFR less than 30 ml/min/1.73 m2 estimated from serum creatinine by applying Cockcroft-Gault equation 13 or chronic dialysis Known HIV, HBV, or HCV infection Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: Enoxaparin 40 mg s.c.<br>Subcutaneous enoxaparin (Klexane®, Sanofi-Aventis) 40 mg thromboprophylaxis every 24 hours for three days (72 hours) | Drug: Enoxaparin<br> <br> |
| Active Comparator: Enoxaparin 40 mg i.v.<br>Enoxaparin thromboprophylaxis (40 mg) daily as continuous intravenous infusion for three days (72 hours) | Drug: Enoxaparin<br> <br> |
| Active Comparator: Enoxaparin 0.5 mg/kg s.c.<br>Subcutaneous enoxaparin (Klexane®, Sanofi-Aventis) 0.5 mg/kg thromboprophylaxis twice a day for three days (72 hours) | Drug: Enoxaparin<br> <br> |
| Active Comparator: Enoxaparin 1 mg/kg i.v.<br>Enoxaparin thromboprophylaxis 1 mg/kg daily as continuous intravenous infusion for three days (72 hours) | Drug: Enoxaparin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-Xa concentration maximum 0-24h (Cmax0-24h) | Anti-Xa concentration maximum level calculated from measured values during 0-24h after initiation of enoxaparin. | 0-24h after initiation of enoxaparin | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-Xa concentration maximum 25-72 h (Cmax25-72h) | Anti-Xa concentration maximum level calculated from measured values 25-72h after the initiation of enoxaparin. | 25-72 h after initiation of enoxaparin | 
| Anti-Xa trough concentartion at 72 h (C72h) | Anti-Xa concentration at the of 72h study period | 72 h after the initiation of enoxaparin | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Venous thromboembolism, pulmonary embolism, thromboprophylaxis, anticoagulant, anti-FXa, low-molecular weight heparin, enoxaparin