Twice Daily Enoxaparin Prophylaxis in Reconstructive Surgery Patients

Optimization of Enoxaparin Prophylaxis Using Real-time Anti-Factor Xa Levels in Major Reconstructive Surgery Patients

Blood clots that form in the extremities (deep venous thrombosis) and lungs (pulmonary embolus) are feared complications of reconstructive surgery. One in ten patients with symptomatic pulmonary embolus will be dead in 60 minutes. Patients with deep venous thrombosis can develop the post-thrombotic syndrome, known to be a major driver of poor quality of life. These phenomena, broadly known as venous thromboembolism (VTE), have substantial downstream ramifications, and the US Surgeon General and the American Society of Plastic Surgeons (ASPS), among others, have underscored the importance of VTE prevention in surgical patients. Reconstructive surgery, most commonly performed to fix traumatic injuries or defects after cancer excision, often involves borrowing tissue from adjacent or distant areas on the body; reconstructive surgery patients can routinely have surgical injury involving 20% or more of their total body surface area. Injury and resultant inflammation are known to increase metabolism of certain drugs, including those used to prevent VTE after surgery.

Enoxaparin is a blood-thinning medication that decreases likelihood of blood clot formation. Previous research has shown that reconstructive surgery patients who are given enoxaparin after surgery are less likely to develop VTE. However, despite receiving of a standard dose of enoxaparin, many patients still develop this life-threatening complication. The investigators believe that patients metabolize enoxaparin differently based on the degree of surgical injury created during reconstruction, and seek to critically examine enoxaparin metabolism in reconstructive surgery patients. The proposed research will evaluate how enoxaparin affects the blood based on standard, ASPS-recommended dosing after reconstructive surgeries; the investigators will also examine whether the extent of surgical injury alters metabolism as well. Enoxaparin effectiveness will be tracked using anti-Factor Xa (aFXa) levels. If subtherapeutic aFXa levels are observed, the study will also design, implement and test a clinical enoxaparin dose-adjustment protocol to achieve appropriate post-operative aFXa levels. Further research based on these data will examine reduction in VTE risk when aFXa-driven enoxaparin dosing is used.

Study Overview

• Status: Completed
• Conditions: Venous Thromboembolism; Deep Venous Thrombosis; Pulmonary Embolus
• Intervention / Treatment: Drug: Twice daily enoxaparin prophylaxis; Drug: Real time dose adjustment

Detailed Description

The ultimate goal of the investigators research is to better understand the interplay between enoxaparin dosing, degree of surgical injury, and blood clots after major reconstructive surgery. Ultimately, this research will expand medicine's understanding of why post-operative VTE occurs, will allow the investigators to individualize a patient's VTE prophylaxis strategy based on their unique characteristics, and will further improve patient safety after reconstructive surgery.

• Study Type: Interventional
• Enrollment (Actual): 118
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Hospitals

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria:

• Adult patients having plastic and reconstructive surgery who are placed on twice daily enoxaparin prophylaxis after surgery.

Exclusion criteria:

• 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
• Epidural anesthesia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Enoxaparin prophylaxis; All enrolled patients will receive twice daily enoxaparin prophylaxis. Patients with identified out of range peak anti-Xa levels will receive real time dose adjustment and will be considered as the experimental arm.	Drug: Twice daily enoxaparin prophylaxis; Patients will have peak and trough steady state anti-Xa levels drawn. For patients with out of range peak levels, real time enoxaparin dose adjustment using a clinical protocol will be performed. Repeat steady state levels will be checked.; Other Names: Lovenox
Experimental: Real time dose adjustment; Patients with identified out of range peak anti-Xa levels will receive real time enoxaparin dose adjustment	Drug: Real time dose adjustment; Patients will have peak and trough steady state anti-Xa levels drawn. For patients with out of range peak levels, real time enoxaparin dose adjustment using a clinical protocol will be performed. Repeat steady state levels will be checked.; Other Names: Lovenox

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with a 90-day VTE (either a 90-day DVT or 90-day PE)	Outcome measure number one will be deep venous thrombosis or pulmonary embolus confirmed with imaging within 90 days of the initial surgery.	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with a 90-day re-operative hematoma	Outcome number two will be bleeding (hematoma) requiring return to the operating room within 90 days of the initial operation.	90 days

Collaborators and Investigators

• Sponsor: University of Utah
• Collaborators: Agency for Healthcare Research and Quality (AHRQ)
• Investigators: Principal Investigator: Christopher Pannucci, MD MS, University of Utah

Publications and helpful links

General Publications

• Pannucci CJ, Fleming KI, Agarwal J, Rockwell WB, Prazak AM, Momeni A. The Impact of Once- versus Twice-Daily Enoxaparin Prophylaxis on Risk for Venous Thromboembolism and Clinically Relevant Bleeding. Plast Reconstr Surg. 2018 Jul;142(1):239-249. doi: 10.1097/PRS.0000000000004517.
• Pannucci CJ, Fleming KI, Momeni A, Prazak AM, Agarwal J, Rockwell WB. Twice-Daily Enoxaparin among Plastic Surgery Inpatients: An Examination of Pharmacodynamics, 90-Day Venous Thromboembolism, and 90-Day Bleeding. Plast Reconstr Surg. 2018 Jun;141(6):1580-1590. doi: 10.1097/PRS.0000000000004379.
• Pannucci CJ, Fleming KI. Comparison of face-to-face interaction and the electronic medical record for venous thromboembolism risk stratification using the 2005 Caprini score. J Vasc Surg Venous Lymphat Disord. 2018 May;6(3):304-311. doi: 10.1016/j.jvsv.2017.10.016. Epub 2018 Feb 13.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Actual): June 23, 2017
• Study Completion (Actual): December 6, 2017

Study Registration Dates

• First Submitted: February 3, 2016
• First Submitted That Met QC Criteria: February 16, 2016
• First Posted (Estimate): February 22, 2016

Study Record Updates

• Last Update Posted (Actual): October 19, 2018
• Last Update Submitted That Met QC Criteria: October 17, 2018
• Last Verified: October 1, 2018

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; Enoxaparin sodium
• Other Study ID Numbers: 86052

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Deidentified data will be shared.
• IPD Sharing Time Frame: 9/4/18
• IPD Sharing Access Criteria: American Society of Plastic Surgeons
• IPD Sharing Supporting Information Type: Statistical Analysis Plan (SAP)

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