Traumatic Injury, Venous Thromboembolism
Conditions
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).
Interventions
DRUGEnoxaparin 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.
DRUGEnoxaparin 30 mg q8h
Patients receive enoxaparin 30 mg every 8 hours.
Sponsors
United States Air Force
University of Cincinnati
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Initial AT-III Activity -- Control Group vs. Intervention Group Prior to Randomization | After third dose of enoxaparin 30mg q12h, which will typically be on Day 2 of enoxaparin | 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 |
Countries
United States
Participant flow
Pre-assignment details
1496 screened for eligibility. 1393 excluded. 51 in control group (anti-Xa 0.1 IU/mL or greater); 52 in intervention group (anti-Xa \< 0.1 IU/mL) 52 patients in the intervention group underwent 1:1 randomization to the two intervention study arms: 26 patients in 40 mg every 12 hours with escalation to 50 mg every 12 hours and 26 patients in 30 mg every 8 hours.
Participants by arm
| Arm | Count |
|---|---|
| Control: 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 | 47 |
| 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 | 51 |
| Total | 98 |
Baseline characteristics
| Characteristic | Control: Serum Anti-Xa >= 0.1 IU/mL | Intervention: Serum Anti-Xa < 0.1 IU/mL | Total |
|---|---|---|---|
| Age, Continuous Age | 38 years | 41 years | 41 years |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 18 Participants | 13 Participants | 31 Participants |
| Sex: Female, Male Male | 29 Participants | 38 Participants | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 0 / 52 |
| other Total, other adverse events | 0 / 51 | 0 / 51 |
| serious Total, serious adverse events | 0 / 51 | 0 / 51 |
Outcome results
Primary
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
Time frame: After third dose of enoxaparin 30mg q12h, which will typically be on Day 2 of enoxaparin
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Control Group | Initial AT-III Activity -- Control Group vs. Intervention Group Prior to Randomization | 87 Percent AT-III activity (%) |
| Intervention Group | Initial AT-III Activity -- Control Group vs. Intervention Group Prior to Randomization | 82 Percent AT-III activity (%) |
p-value: 0.092Wilcoxon (Mann-Whitney)