Clinical trial NCT02412982: Evaluation of Venous Thromboembolism Prevention in High-Risk Trauma Patients
Official title: Evaluation of Venous Thromboembolism Prevention in High-Risk Trauma Patients: A Prospective Randomized Trial of Standard Enoxaparin Versus Two Anti-Xa Adjusted Dosing Strategies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Traumatic Injury
Venous Thromboembolism
Lead sponsor: University of Cincinnati
Sponsor class: OTHER
Collaborators: name: United States Air Force
First posted: 2015-04-09
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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).

Eligibility criteria: 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

Primary outcomes:
measure: Initial AT-III Activity -- Control Group vs. Intervention Group Prior to Randomization
timeFrame: After third dose of enoxaparin 30mg q12h, which will typically be on Day 2 of enoxaparin
Secondary outcomes:
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
Study officials:
affiliation: UC Health - University of Cincinnati Medical Center
name: Molly Droege, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.