Evaluation of Venous Thromboembolism Prevention in High-Risk Trauma Patients

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

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

Conditions
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Traumatic Injury, Venous Thromboembolism

Intervention / Treatment
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* Drug: Enoxaparin 40 mg q12h
* Drug: Enoxaparin 30 mg q8h


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Serum anti-Xa >= 0.1 IU/mL<br>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<br>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<br>* 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.<br>* Other names: no other name;|
| Active Comparator: Anti-Xa <0.1 IU/mL:enoxaparin 30 mg q8h<br>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<br>* Patients receive enoxaparin 30 mg every 8 hours.<br>* Other names: no other name;|
| No Intervention: Serum anti-Xa < 0.1 IU/mL<br>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?
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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 |