: Pharmacokinetics of Enoxaparin After Coronary Artery Bypass Graft Surgery

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

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.

Study Overview

• Status: Completed
• Conditions: Venous Thromboembolism; Pulmonary Embolism; Thromboprophylaxis
• Intervention / Treatment: Drug: Enoxaparin

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 Type: Interventional
• Enrollment (Actual): 85
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Kati Järvelä, PhD; Phone Number: +358331164869; Email: kati.jarvela@sydansairaala.fi
• Study Contact Backup: Name: Maria Parviainen, MD; Email: maria.parviainen@tuni.fi

Study Locations

• Finland
  • Pirkanmaa
    • Tampere, Pirkanmaa, Finland, 33521
      • Tampere university Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical outcomes	Postoperative bleeding, DVT, pulmonary embolism, 90 day mortality	0-90 days after initiation of enoxaparin

Collaborators and Investigators

• Sponsor: Tampere University Hospital
• Collaborators: Heart Hospital, Tampere University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2016
• Primary Completion (Actual): March 31, 2023
• Study Completion (Actual): March 31, 2023

Study Registration Dates

• First Submitted: June 15, 2015
• First Submitted That Met QC Criteria: June 16, 2015
• First Posted (Estimate): June 17, 2015

Study Record Updates

• Last Update Posted (Actual): May 9, 2023
• Last Update Submitted That Met QC Criteria: May 5, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: anticoagulant; Venous thromboembolism; pulmonary embolism; enoxaparin; thromboprophylaxis; low-molecular weight heparin; anti-FXa
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Thromboembolism; Venous Thromboembolism; Pulmonary Embolism; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Enoxaparin
• Other Study ID Numbers: 290115-1