Evaluation of Venous Thromboembolism Prevention in High-Risk Trauma Patients

Evaluation of Venous Thromboembolism Prevention in High-Risk Trauma Patients: A Prospective Randomized Trial of Standard Enoxaparin Versus Two Anti-Xa Adjusted Dosing Strategies

This is a pilot study to determine if anti-thrombin III (AT-III) serum concentrations differ between patients with normal versus subtherapeutic anti-Xa trough concentrations when placed on enoxaparin 30 mg twice daily for VTE prophylaxis. Secondarily, this study will compare two enoxaparin dosing strategies.

Study Overview

• Status: Completed
• Conditions: Venous Thromboembolism; Traumatic Injury
• Intervention / Treatment: Drug: Enoxaparin 40 mg q12h; Drug: Enoxaparin 30 mg q8h

Detailed Description

This is a pilot study to determine if AT-III serum concentrations differ between patients with normal (>= 0.1 IU/mL) versus subtherapeutic (<0.1 IU/mL) anti-Xa trough concentrations when placed on enoxaparin 30 mg twice daily for venous thromboembolism (VTE) prophylaxis. Secondarily, this study will compare two enoxaparin dosing strategies: standard 30 mg twice daily and a dosing strategy based on trough anti-Xa values in high-risk trauma patients.

Specific aims include: 1) to compare the extent of reduced AT-III activity between patients with trough anti-Xa >= 0.1 IU/mL and < 0.1 IU/mL upon initial assay; 2) to determine the proportion of patients who reach goal anti-Xa and the time to goal anti-Xa achievement between two interventional dosing strategies: enoxaparin 40 mg every 12 hours (with consideration to increase to 50 mg every 12 hours if recheck anti-Xa is not at goal) and enoxaparin 30 mg every eight hours; 3) to compare anti-Xa enoxaparin dosing strategies based on VTE, bleeding rates, transfusion requirements, drug discontinuation rate and bioaccumulation, and 4) to determine patient-specific factors that correlate to subtherapeutic anti-Xa such as serial AT-III activity, weight, body mass index, age, cumulative fluid administration, and thromboelastography (TEG).

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45216
      • University of Cincinnati Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Multi-system trauma
• Anticipated length of stay of at least 72 hours
• At high risk (risk adjustment profile [RAP] >= 5) and initiated on enoxaparin 30 mg every 12 hours per VTE prophylaxis protocol
• No counterindication to trauma team VTE prophylaxis protocol (e.g., intracranial bleeding, incomplete spinal cord injury with hematoma within 24 hours post injury, ongoing hemorrhage, uncorrected coagulopathy, >= grade IV liver or spleen injury, intraocular injury)

Exclusion Criteria:

• Renal dysfunction (creatinine clearance < 30 mL/min or on continuous renal replacement therapy)
• Weight < 50 kg or > 150 kg
• Platelet count < 50,000
• Allergy to heparin or low molecular weight heparin
• On therapeutic anticoagulation on admission or requiring it within 24 hours of admission
• Isolated intracranial hemorrhage
• Known hyperbilirubinemia (serum bilirubin > 6.6 mg/dL)
• Pregnancy
• Incarceration

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Serum anti-Xa >= 0.1 IU/mL; Patients with serum anti-Xa level >= 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours
Active Comparator: Anti-Xa <0.1 IU/mL:enoxaparin 40 mg q12h; Patients with serum anti-Xa level < 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours who then receive enoxaparin 40 mg every 12 hours. If repeat steady state trough anti-Xa is subtherapeutic, dose will be increased to enoxaparin 50 mg every 12 hours.	Drug: Enoxaparin 40 mg q12h; Patients receive enoxaparin 40 mg every 12 hours. Dose will be escalated to enoxaparin 50 mg every 12 hours if steady state trough concentration is still subtherapeutic.; Other Names: no other name
Active Comparator: Anti-Xa <0.1 IU/mL:enoxaparin 30 mg q8h; Patients with serum anti-Xa level < 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours who then receive enoxaparin 30 mg every eight hours	Drug: Enoxaparin 30 mg q8h; Patients receive enoxaparin 30 mg every 8 hours.; Other Names: no other name
No Intervention: Serum anti-Xa < 0.1 IU/mL; Patients with serum anti-Xa level < 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Initial AT-III Activity -- Control Group vs. Intervention Group Prior to Randomization	Serum AT-III (% activity) will be compared between the control group and the intervention group patients (combined) after the third dose of enoxaparin 30 mg every 12 hours once initiated at the discretion of the trauma service per current VTE prophylaxis protocol	After third dose of enoxaparin 30mg q12h, which will typically be on Day 2 of enoxaparin

Collaborators and Investigators

• Sponsor: University of Cincinnati
• Collaborators: United States Air Force
• Investigators: Principal Investigator: Molly Droege, PharmD, UC Health - University of Cincinnati Medical Center

Publications and helpful links

General Publications

• Droege ME, Droege CA, Philpott CD, Webb ML, Ernst NE, Athota K, Wakefield D, Dowd JR, Gomaa D, Robinson BHR, Hanseman D, Elterman J, Mueller EW. Impact of antithrombin III and enoxaparin dosage adjustment on prophylactic anti-Xa concentrations in trauma patients at high risk for venous thromboembolism: a randomized pilot trial. J Thromb Thrombolysis. 2021 Nov;52(4):1117-1128. doi: 10.1007/s11239-021-02478-4. Epub 2021 May 12.

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Actual): January 1, 2019
• Study Completion (Actual): January 1, 2019

Study Registration Dates

• First Submitted: February 24, 2015
• First Submitted That Met QC Criteria: April 6, 2015
• First Posted (Estimate): April 9, 2015

Study Record Updates

• Last Update Posted (Actual): October 25, 2021
• Last Update Submitted That Met QC Criteria: October 22, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Wounds and Injuries; Thromboembolism; Venous Thromboembolism; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Enoxaparin; Enoxaparin sodium
• Other Study ID Numbers: Droege2015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No