Enoxaparin Metabolism in Reconstructive Surgery Patients

Venous Thromboembolism Clinical Trial

Official title:

Enoxaparin Metabolism in Reconstructive Surgery Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02411292
• Other study ID #: IRB 00079118
• Status: Completed
• Phase: Phase 2
• Start date: March 2015
• Est. completion date: June 2016

Study information

• Verified date: October 2018
• Source: University of Utah
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Venous thromboembolism (VTE) is a leading cause of death among hospitalized patients, and is an important patient safety issue in plastic surgery. Previous work has shown that enoxaparin prophylaxis can prevent many post-operative VTE events, and current American Society of Plastic Surgeons guidelines support enoxaparin prophylaxis for high-risk patients. Highest risk patients often have cancer or trauma reconstruction. Primary outcomes include 1) peak and trough steady-state aFXa levels in response to standard and escalated doses of enoxaparin and 2) the proportion of patients with appropriate aFXa levels pre and post initiation of a clinical protocol for enoxaparin dose adjustment. The investigators expect that standard dosing will result in inadequate aFXa peak and trough levels, and that the clinical dose adjustment protocol will significantly improve the proportion of in-range aFXa levels. The investigators will also develop a linear regression-based equation to calculate, based on patient-level factors, the required dose of enoxaparin to generate in-range aFXa levels. This research may show that the current "one size fits all" approach to enoxaparin prophylaxis is insufficient. In the trauma and orthopaedic populations, patients with low initial aFXa levels are significantly more likely to develop deep venous thrombosis. Thus, this study has important implications for appropriate enoxaparin dose magnitude and frequency, and may ultimately help to decrease the substantial morbidity and mortality associated with post-operative VTE.

Description:

Venous thromboembolism (VTE) is a leading cause of death among hospitalized patients, and is an important patient safety issue in plastic surgery. Previous work has shown that enoxaparin prophylaxis can prevent many post-operative VTE events, and current American Society of Plastic Surgeons guidelines support enoxaparin prophylaxis for high-risk patients. However, the Plastic Surgery Foundation-funded Venous Thromboembolism Prevention Study showed that 1 in 25 highest risk patients still had a "breakthrough" VTE event despite receipt of guideline-compliant enoxaparin prophylaxis. Highest risk patients often have cancer or trauma reconstruction. These surgeries may have surgical injury that is equal in scope to patients with traumatic or thermal injury. Previous work in patients with traumatic or thermal injury has shown that enoxaparin metabolism, measured by anti-factor Xa (aFXa) level, is substantially increased: a higher degree of injury is associated with higher enoxaparin dose requirements to achieve prophylactic levels. "Breakthrough" VTE events may occur in plastic and reconstructive surgery patients due to inadequate enoxaparin dosing. The investigators will examine enoxaparin pharmacokinetics and test whether a clinical protocol for real-time enoxaparin dose adjustment can favorably alter the proportion of patients with in-range aFXa levels. Primary outcomes include 1) peak and trough steady-state aFXa levels in response to standard and escalated doses of enoxaparin and 2) the proportion of patients with appropriate aFXa levels pre and post initiation of a clinical protocol for enoxaparin dose adjustment. The investigators expect that standard dosing will result in inadequate aFXa peak and trough levels, and that the clinical dose adjustment protocol will significantly improve the proportion of in-range aFXa levels. The investigators will also develop a linear regression-based equation to calculate, based on patient-level factors, the required dose of enoxaparin to generate in-range aFXa levels. This research may show that the current "one size fits all" approach to enoxaparin prophylaxis is insufficient. In the trauma and orthopaedic populations, patients with low initial aFXa levels are significantly more likely to develop deep venous thrombosis. Thus, this study has important implications for appropriate enoxaparin dose magnitude and frequency, and may ultimately help to decrease the substantial morbidity and mortality associated with post-operative VTE.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 110
• Est. completion date: June 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Inclusion criteria will include:

• adult (age =18) patients presenting for reconstructive surgery under general anesthesia.

• expected post-operative stay will be at least three days to allow peak aFXa levels to be drawn.

• eligible patients will include those having major reconstructive surgery.

Exclusion Criteria:

Exclusion criteria will include:

• contraindication to use of enoxaparin,

• intracranial bleeding/stroke,

• hematoma or bleeding disorder,

• known heparin-induced thrombocytopenia,

• creatinine clearance =30mL/min,

• serum creatinine >1.6mg/dL, or epidural anesthesia.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Enoxaparin
Enrolled patients will receive real-time monitoring of peak and trough steady state anti-Xa levels. Out-of-range patients will receive real time dose adjustment of Enoxaparin using a clinical protocol developed with our inpatient pharmacists.

Locations

Country	Name	City	State
United States	University of Utah	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	Number of Participants With Venous Thromboembolism Events	Any symptomatic venous thromboembolism events, including deep venous thrombosis or pulmonary embolus occurring within 90 days of surgery	90 days
Primary	Number of Participants With Bleeding Events	Bleeding events requiring alteration in the course of care within 90 days of surgery	90 days