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

Venous Thromboembolism Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02704052
• Other study ID #: IRB_00086103
• Status: Completed
• Phase: Early Phase 1
• Start date: March 2016
• Est. completion date: October 2018

Study information

• Verified date: May 2019
• Source: University of Utah
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 116
• Est. completion date: October 2018
• Est. primary completion date: July 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adults, (age=18)

• Patients who have had surgery with general anesthesia.

• Post-operative stay will be =2 days

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.

Related Conditions & MeSH terms

• Deep Venous Thrombosis
• Pulmonary Embolism
• Pulmonary Embolus
• Thromboembolism
• Thrombosis
• Venous Thromboembolism
• Venous Thrombosis

Intervention

Drug:
• Real time enoxaparin dose adjustment
Patients will have steady state peak and trough anti-Xa levels drawn after their third enoxaparin dose. Patients with out of range peak anti-Xa levels will receive real time enoxaparin dose adjustment followed by repeat peak and trough anti-Xa levels.
• Standard enoxaparin dose
Patients will be placed on enoxaparin prophylaxis per their surgeon's discretion.

Locations

Country	Name	City	State
United States	University of Utah Hospitals	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
University of Utah

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Venous thromboembolism	Symptomatic 90-day VTE confirmed with imaging	90 days
Secondary	Re-operative hematoma	Bleeding requiring return to the operating room within 90 days	90 days