Weight-Based Enoxaparin Dosing and Real-Time Dose Adjustment in Orthopaedic Trauma

The rates of Venous thromboembolism (VTE) after orthopedic surgery are as high as 40-60% without prophylactic measures. Enoxaparin, a low-molecular-weight heparin, produces an anticoagulant effect by binding antithrombin, thereby accelerating antithrombin's inactivation of coagulation factor Xa (FXa), thus decreasing the likelihood of clot formation. Despite standard dosing enoxaparin prophylaxis, VTE rates in post-operative orthopedic trauma patients remain as high as 12.2%.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 anti-Factor Xa (aFXa) levels. Outcomes will include peak and trough steady-state aFXa levels in response to standard and escalated doses of enoxaparin and the incidence of venous thromboembolism and bleeding events post-surgery. 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.

Study Overview

• Status: Completed
• Conditions: Deep Vein Thrombosis; Venous Thromboembolism; Pulmonary Embolus
• Intervention / Treatment: Drug: Enoxaparin

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Receiving orthopedic trauma surgery
• Able to have enoxaparin initiated within 36 hours after procedure

Exclusion Criteria:

• Intracranial bleeding/stroke
• bleeding disorder
• heparin-induced thrombocytopenia
• creatinine clearance < 30 mL/minute
• epidural catheter
• serum creatinine > 1.6 mg/dL

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Enoxaparin Metabolism; Eligible patients will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose. For patients in-range (levels 0.2-0.4 IU/mL), 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.

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Bleeding Events	Bleeding events requiring alteration in the course of care within 90 days of surgery	90 days
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

Collaborators and Investigators

• Sponsor: University of Utah

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2017
• Primary Completion (Actual): June 30, 2019
• Study Completion (Actual): October 29, 2019

Study Registration Dates

• First Submitted: November 7, 2017
• First Submitted That Met QC Criteria: November 7, 2017
• First Posted (Actual): November 13, 2017

Study Record Updates

• Last Update Posted (Estimated): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 3, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Thrombosis; Venous Thrombosis; Thromboembolism; Venous Thromboembolism; Pulmonary Embolism; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Enoxaparin
• Other Study ID Numbers: 102526

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No