Enoxaparin Metabolism in Reconstructive Surgery Patients

Phase 2

Completed

Conditions: Deep Venous Thrombosis
Reconstructive Surgery
Venous Thromboembolism
Pulmonary Embolus

Interventions: Drug: Enoxaparin

Registration Number: NCT02411292

Lead Sponsor: University of Utah

Brief 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.

Detailed 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 & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 110

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Enoxaparin metabolism	Enoxaparin	Eligible patients will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose. For patients in-range (levels 0.3-0.5IUmL), no intervention will be undertaken. For patients out of range, enoxaparin dose will be adjusted according to an established dose adjustment algorithm. Repeat levels will be checked after the third administration of the new dose.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Bleeding Events	90 days	Bleeding events requiring alteration in the course of care within 90 days of surgery
Number of Participants With Venous Thromboembolism Events	90 days	Any symptomatic venous thromboembolism events, including deep venous thrombosis or pulmonary embolus occurring within 90 days of surgery

Secondary Outcome Measures