Real-time Anti-Factor Xa Measurements in Surgical Patients to Examine Enoxaparin Metabolism and Optimize Enoxaparin Dose

Early Phase 1

Completed

• Conditions: Deep Venous Thrombosis; Pulmonary Embolus; Venous Thromboembolism
• Interventions: Drug: Standard enoxaparin dose; Drug: Real time enoxaparin dose adjustment

• Registration Number: NCT02704052
• Lead Sponsor: University of Utah

Brief Summary

Venous thromboembolism (VTE) encompasses deep venous thrombosis and pulmonary embolus, and is the proximate cause of death in over 100,000 hospitalized patients per year.

This project will critically examine the pharmacokinetics of prophylactic doses of enoxaparin in surgical patients, and will evaluate how alteration of enoxaparin dose magnitude and frequency affects peak and trough aFXa levels as well as risk for re-operative hematoma. If subtherapeutic aFXa levels are observed, the study will design, implement and test a clinical protocol to optimize post-operative aFXa levels. Although not an explicit Aim, this study will also provide important preliminary data on VTE rates in surgical patients with in range and out of range aFXa levels.

Detailed Description

Venous thromboembolism (VTE) encompasses deep venous thrombosis and pulmonary embolus, and is the proximate cause of death in over 100,000 hospitalized patients per year. To put this in better context, VTE kills more people each year than the annual morbidity from motor vehicle crashes and breast cancer combined. Surgeons commonly provide enoxaparin, a low molecular weight heparin, for VTE prophylaxis. Enoxaparin's activity is quantified by anti-Factor Xa (aFXa) levels. Studies of enoxaparin metabolism in patients with traumatic injury, thermal injury, or those undergoing reconstructive surgery have shown that standard dosing can result in inadequate aFXa levels, likely from the hypermetabolic state associated with significant injury. Small studies have associated subtherapeutic aFXa levels with increased risk for life or limb-threatening VTE events. Prior work from has shown that 2-10% of highest risk surgical patients have a VTE event despite enoxaparin prophylaxis. The investigators believe that surgical patients would benefit from an individualized dosing regimen for enoxaparin prophylaxis and that individualized dosing will decrease observed rates of life or limb-threatening post-operative VTE events.

This project will critically examine the pharmacokinetics of prophylactic doses of enoxaparin in surgical patients, and will evaluate how alteration of enoxaparin dose magnitude and frequency affects peak and trough aFXa levels as well as risk for re-operative hematoma. If subtherapeutic aFXa levels are observed, the study will design, implement and test a clinical protocol to optimize post-operative aFXa levels. Although not an explicit Aim, this study will also provide important preliminary data on VTE rates in surgical patients with in range and out of range aFXa levels.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2016-03
• Study First Submitted: 2016-03-07
• Study First Submitted QC: 2016-03-07
• Study First Posted: 2016-03-09
• Primary Completion: 2018-07
• Study Completion: 2018-10
• Status Verified: 2019-05
• Last Update Submitted: 2019-05-21
• Last Update Posted: 2019-05-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 116

Inclusion Criteria

• Adults, (age≥18)
• Patients who have had surgery with general anesthesia.
• Post-operative stay will be ≥2 days

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Exclusion Criteria

• Contradiction to use enoxaparin
• History of intracranial bleeding/stroke, hematoma or bleeding disorder, heparin-induced thrombocytopenia positive, and heparin-induced thrombocytopenia positive
• Creatinine clearance ≤ 30mL/min
• Serum creatinine >1.6mg/dL
• Epidural anesthesia
• Patients placed on non-enoxaparin chemoprophylaxis regimens per their surgeon's discretion.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard enoxaparin dose	Standard enoxaparin dose	We will identify a convenience sample of surgical patients placed on enoxaparin prophylaxis at their attending surgeon's discretion-the proposed research will not dictate the initial enoxaparin dose magnitude or frequency. However, we will identify patients already on enoxaparin, evaluate peak and trough steady state aFXa levels, and adjust patient's dose if necessary based on steady state aFXa levels. Eligible patients will have enoxaparin prophylaxis started within 36 after surgery at their surgeon's discretion. Steady state peak and trough aFXa levels will be drawn at 4 and 12 hours, respectively, after the third enoxaparin dose. Goal peak aFXa levels will be 0.2-0.4 IU/mL for twice daily dosing and 0.3-0.5 IU/mL for once daily dosing.
Real time enoxaparin dose adjustment	Real time enoxaparin dose adjustment	Patients with identified out of range levels will receive pharmacist-driven real time enoxaparin dose adjustment and will receive followup steady state peak and trough aFXa levels. aFXa monitoring will be discontinued when in range peak levels are obtained, when enoxaparin prophylaxis is discontinued at surgeon discretion, or when the patient is discharged. Patients may be continued on enoxaparin prophylaxis after discharge per attending surgeon discretion but aFXa levels will not be followed in the outpatient environment.

Primary Outcome Measures

Name	Time	Method
Venous thromboembolism	90 days	Symptomatic 90-day VTE confirmed with imaging

Secondary Outcome Measures

Name	Time	Method
Re-operative hematoma	90 days	Bleeding requiring return to the operating room within 90 days

Trial Locations

Locations (1)

University of Utah Hospitals; 🇺🇸 Salt Lake City, Utah, United States