Antithrombin to Improve Thromboprophylaxis and Reduce the Incidence of Trauma-Related Venous Thromboembolism

Study Overview
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Brief Summary
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The purpose of this study is to determine if additional interventions will assist with decreasing the risk and/or severity of thromboembolism (clotting complications) in patients who have experienced a major traumatic event.

Official Title
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Antithrombin to Improve Thromboprophylaxis and Reduce the Incidence of Trauma-Related Venous Thromboembolism (TRAIT)

Conditions
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Trauma Injury, Thromboembolism, Venous Thromboembolism

Intervention / Treatment
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* Drug: Thrombate infusion
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Highest level of trauma activation or upgrade to highest level Polytraumatic injuries OR pelvic/long bone fracture Admission to trauma ICU or Surgical Intermediate Care Unit (SIMU) Informed consent obtained Exclusion Criteria: Prisoners (defined as those directly admitted from correctional facility) Known or suspected pregnancy ≥ 20% total body surface area (TBSA) burned Nonsurvivable head injuries Known hematologic or immunologic disorders Known prehospital anticoagulant use Patients initially placed on unfractionated heparin for thromboprophylaxis Known allergy to Antithrombin or it's components Enrollment in another interventional study unless approved by Trial Principal Investigator

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multi-center, placebo-controlled, randomized, double-blind study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thrombate infusion<br> | Drug: Thrombate infusion<br>* Bolus intravenous infusion of Thrombate will be given to achieve antithrombin (AT) activity levels at 150% before the 3rd dose of Enoxaparin. The dose will be based on patient weight.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Normal Saline will be given as one time IV after the 3rd dose of Enoxaparin. The dose will be based on patient weight.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with incidences of venous thromboembolism (VTE ) |  | 14 days post hospital admission | 
| Number of participants with incidence of antifactor Xa (anti-FXa) of ≥0.2 IU/mL |  | 14 days post hospital admission | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time taken to achieve anti-FXa of ≥0.2 IU/mL |  | 14 days post hospital admission | 
| Number of enoxaparin dose escalations |  | from the time of hospital admission to the time of hospital discharge or 30 days (whichever occurs first) | 
| Number of incidences of participants with other thrombotic complications (arterial thrombosis, myocardial infarction, stroke) |  | from the time of hospital admission to the time of hospital discharge or 30 days (whichever occurs first) | 
| Number of incidences of participants with bleeding events (interoperative bleeding, abdominal bleeding) |  | from the time of hospital admission to the time of hospital discharge or 30 days (whichever occurs first) | 
| Number of hospital free days |  | from the time of hospital admission to the time of hospital discharge or 30 days (whichever occurs first) | 
| Number of Ventilator free days |  | from the time of hospital admission to the time of hospital discharge or 30 days (whichever occurs first) | 
| Number of ICU free days |  | from the time of hospital admission to the time of hospital discharge or 30 days (whichever occurs first) | 
| Level of Anti-FXa |  | from the time of hospital admission up to hospital day 7 | 
| Antithrombin (AT) activity level |  | from the time of hospital admission up to hospital day 7 | 
| Change in level of the endothelial marker syndecan-1 as assessed by a blood test |  | time of hospital admission, day1, day2, day 3, day 4, day 5, day6, day 7 | 
| Change in level of the endothelial marker thrombomodulin as assessed by a blood test |  | From the time of hospital admission to day 7 | 
| Change in level of Inflammatory marker Tumor necrosis factor alpha (TNFα) as assessed by a blood test |  | From time of hospital admission to day 7 | 
| Change in level of Inflammatory marker Interleukin-8 (IL-8) as assessed by a blood test |  | From time of hospital admission to day 7 | 
| Change in level of Inflammatory marker Interleukin-6(IL-6) as assessed by a blood test |  | time of hospital admission, day1, day2, day 3, day 4, day 5, day6, day 7 | 
| Change in level of Inflammatory marker Interleukin-1 beta (IL1b) as assessed by a blood test |  | From time of hospital admission to day 7 | 
| Change in level of Inflammatory marker Interleukin-1 alpha (IL1a) as assessed by a blood test |  | From time of hospital admission to day 7 | 
| Change in level of Inflammatory marker Interferon -gamma (INFg) as assessed by a blood test |  | From time of hospital admission to day 7 | 
| Number of participants with In-hospital mortality |  | from the time of hospital admission to the time of hospital discharge or 30 days (whichever occurs first) |