Deep Vein Thrombosis, Pulmonary Embolus, Venous Thromboembolism
Conditions
Brief summary
The rates of Venous thromboembolism (VTE) after orthopedic surgery are as high as 40-60% without prophylactic measures. Enoxaparin, a low-molecular-weight heparin, produces an anticoagulant effect by binding antithrombin, thereby accelerating antithrombin's inactivation of coagulation factor Xa (FXa), thus decreasing the likelihood of clot formation. Despite standard dosing enoxaparin prophylaxis, VTE rates in post-operative orthopedic trauma patients remain as high as 12.2%.The investigators will examine enoxaparin pharmacokinetics and test whether a clinical protocol for real-time enoxaparin dose adjustment can favorably alter the proportion of patients with in-range anti-Factor Xa (aFXa) levels. Outcomes will include peak and trough steady-state aFXa levels in response to standard and escalated doses of enoxaparin and the incidence of venous thromboembolism and bleeding events post-surgery. In the trauma and orthopaedic populations, patients with low initial aFXa levels are significantly more likely to develop deep venous thrombosis. Thus, this study has important implications for appropriate enoxaparin dose magnitude and frequency, and may ultimately help to decrease the substantial morbidity and mortality associated with post-operative VTE.
Interventions
DRUGEnoxaparin
Enrolled patients will receive real-time monitoring of peak and trough steady state anti-Xa levels. Out-of-range patients will receive real time dose adjustment of Enoxaparin using a clinical protocol developed with our inpatient pharmacists.
Sponsors
University of Utah
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Receiving orthopedic trauma surgery * Able to have enoxaparin initiated within 36 hours after procedure
Exclusion criteria
* Intracranial bleeding/stroke * bleeding disorder * heparin-induced thrombocytopenia * creatinine clearance \< 30 mL/minute * epidural catheter * serum creatinine \> 1.6 mg/dL
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Venous Thromboembolism Events | 90 days | Any symptomatic venous thromboembolism events, including deep venous thrombosis or pulmonary embolus occurring within 90 days of surgery |
| Number of Participants With Bleeding Events | 90 days | Bleeding events requiring alteration in the course of care within 90 days of surgery |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Enoxaparin Metabolism Eligible patients will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose. For patients in-range (levels 0.2-0.4 IU/mL), no intervention will be undertaken. For patients out of range, enoxaparin dose will be adjusted according to an established dose adjustment algorithm. Repeat levels will be checked after the third administration of the new dose.
Enoxaparin: Enrolled patients will receive real-time monitoring of peak and trough steady state anti-Xa levels. Out-of-range patients will receive real time dose adjustment of Enoxaparin using a clinical protocol developed with our inpatient pharmacists. | 80 |
| Total | 80 |
Baseline characteristics
| Characteristic | Enoxaparin Metabolism |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 23 Participants |
| Age, Categorical Between 18 and 65 years | 57 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 80 Participants |
| Sex: Female, Male Female | 36 Participants |
| Sex: Female, Male Male | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 80 |
| other Total, other adverse events | 1 / 80 |
| serious Total, serious adverse events | 0 / 80 |
Outcome results
Primary
Number of Participants With Bleeding Events
Bleeding events requiring alteration in the course of care within 90 days of surgery
Time frame: 90 days
Population: Only 17 participants reached full 90-day follow up~Protocol section, Statistical Methods, Data Analysis and Interpretation, Using an alpha of 0.05 and beta of 0.9, we would need 107 patients to effectively power a similar change for peak aFXa levels in the proposed study. To allow for attrition, we would require n = 137.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Enoxaparin Metabolism | Number of Participants With Bleeding Events | 1 Participants |
Primary
Number of Participants With Venous Thromboembolism Events
Any symptomatic venous thromboembolism events, including deep venous thrombosis or pulmonary embolus occurring within 90 days of surgery
Time frame: 90 days
Population: Only 17 participants reached full 90-day follow up~Protocol section, Statistical Methods, Data Analysis and Interpretation, Using an alpha of 0.05 and beta of 0.9, we would need 107 patients to effectively power a similar change for peak aFXa levels in the proposed study. To allow for attrition, we would require n = 137.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Enoxaparin Metabolism | Number of Participants With Venous Thromboembolism Events | 1 Participants |