: Pharmacokinetics of Enoxaparin After Coronary Artery Bypass Graft Surgery

Phase 4

Completed

• Conditions: Pulmonary Embolism; Thromboprophylaxis; Venous Thromboembolism
• Interventions: Drug: Enoxaparin

• Registration Number: NCT02474212
• Lead Sponsor: Tampere University Hospital

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2015-06-15
• Study First Submitted QC: 2015-06-16
• Study First Posted: 2015-06-17
• Study Start: 2016-05
• Primary Completion: 2023-03-31
• Study Completion: 2023-03-31
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-05
• Last Update Posted: 2023-05-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 85

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Enoxaparin 1 mg/kg i.v.	Enoxaparin	Enoxaparin thromboprophylaxis 1 mg/kg daily as continuous intravenous infusion for three days (72 hours)
Enoxaparin 0.5 mg/kg s.c.	Enoxaparin	Subcutaneous enoxaparin (Klexane®, Sanofi-Aventis) 0.5 mg/kg thromboprophylaxis twice a day for three days (72 hours)
Enoxaparin 40 mg i.v.	Enoxaparin	Enoxaparin thromboprophylaxis (40 mg) daily as continuous intravenous infusion for three days (72 hours)
Enoxaparin 40 mg s.c.	Enoxaparin	Subcutaneous enoxaparin (Klexane®, Sanofi-Aventis) 40 mg thromboprophylaxis every 24 hours for three days (72 hours)

Primary Outcome Measures

Name	Time	Method
Anti-Xa concentration maximum 0-24h (Cmax0-24h)	0-24h after initiation of enoxaparin	Anti-Xa concentration maximum level calculated from measured values during 0-24h after initiation of enoxaparin.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Tampere University Hospital; 🇫🇮 Tampere, Pirkanmaa, Finland