: Pharmacokinetics of Enoxaparin After Coronary Artery Bypass Graft Surgery

Tampere University Hospital

Status and phase: Completed; Phase 4

Conditions: Pulmonary Embolism; Venous Thromboembolism; Thromboprophylaxis

Treatments: Drug: Enoxaparin

Study type: Interventional

Funder types: Other

Identifiers

NCT02474212

290115-1

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 85 patients

Sex: All

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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85 participants in 4 patient groups

Enoxaparin 40 mg s.c.

Active Comparator group

Description:

Subcutaneous enoxaparin (Klexane®, Sanofi-Aventis) 40 mg thromboprophylaxis every 24 hours for three days (72 hours)

Treatment:

Drug: Enoxaparin

Enoxaparin 40 mg i.v.

Active Comparator group

Description:

Enoxaparin thromboprophylaxis (40 mg) daily as continuous intravenous infusion for three days (72 hours)

Treatment:

Drug: Enoxaparin

Enoxaparin 0.5 mg/kg s.c.

Active Comparator group

Description:

Subcutaneous enoxaparin (Klexane®, Sanofi-Aventis) 0.5 mg/kg thromboprophylaxis twice a day for three days (72 hours)

Treatment:

Drug: Enoxaparin

Enoxaparin 1 mg/kg i.v.

Active Comparator group

Description:

Enoxaparin thromboprophylaxis 1 mg/kg daily as continuous intravenous infusion for three days (72 hours)

Treatment:

Drug: Enoxaparin