Deep Venous Thrombosis, Pulmonary Embolus, Reconstructive Surgery, Venous Thromboembolism
Conditions
Brief summary
Venous thromboembolism (VTE) is a leading cause of death among hospitalized patients, and is an important patient safety issue in plastic surgery. Previous work has shown that enoxaparin prophylaxis can prevent many post-operative VTE events, and current American Society of Plastic Surgeons guidelines support enoxaparin prophylaxis for high-risk patients. Highest risk patients often have cancer or trauma reconstruction. Primary outcomes include 1) peak and trough steady-state aFXa levels in response to standard and escalated doses of enoxaparin and 2) the proportion of patients with appropriate aFXa levels pre and post initiation of a clinical protocol for enoxaparin dose adjustment. The investigators expect that standard dosing will result in inadequate aFXa peak and trough levels, and that the clinical dose adjustment protocol will significantly improve the proportion of in-range aFXa levels. The investigators will also develop a linear regression-based equation to calculate, based on patient-level factors, the required dose of enoxaparin to generate in-range aFXa levels. This research may show that the current one size fits all approach to enoxaparin prophylaxis is insufficient. 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.
Detailed description
Venous thromboembolism (VTE) is a leading cause of death among hospitalized patients, and is an important patient safety issue in plastic surgery. Previous work has shown that enoxaparin prophylaxis can prevent many post-operative VTE events, and current American Society of Plastic Surgeons guidelines support enoxaparin prophylaxis for high-risk patients. However, the Plastic Surgery Foundation-funded Venous Thromboembolism Prevention Study showed that 1 in 25 highest risk patients still had a breakthrough VTE event despite receipt of guideline-compliant enoxaparin prophylaxis. Highest risk patients often have cancer or trauma reconstruction. These surgeries may have surgical injury that is equal in scope to patients with traumatic or thermal injury. Previous work in patients with traumatic or thermal injury has shown that enoxaparin metabolism, measured by anti-factor Xa (aFXa) level, is substantially increased: a higher degree of injury is associated with higher enoxaparin dose requirements to achieve prophylactic levels. Breakthrough VTE events may occur in plastic and reconstructive surgery patients due to inadequate enoxaparin dosing. 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 aFXa levels. Primary outcomes include 1) peak and trough steady-state aFXa levels in response to standard and escalated doses of enoxaparin and 2) the proportion of patients with appropriate aFXa levels pre and post initiation of a clinical protocol for enoxaparin dose adjustment. The investigators expect that standard dosing will result in inadequate aFXa peak and trough levels, and that the clinical dose adjustment protocol will significantly improve the proportion of in-range aFXa levels. The investigators will also develop a linear regression-based equation to calculate, based on patient-level factors, the required dose of enoxaparin to generate in-range aFXa levels. This research may show that the current one size fits all approach to enoxaparin prophylaxis is insufficient. 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
Inclusion criteria will include: * adult (age ≥18) patients presenting for reconstructive surgery under general anesthesia. * expected post-operative stay will be at least three days to allow peak aFXa levels to be drawn. * eligible patients will include those having major reconstructive surgery.
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 0.3-0.5IUmL), 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 using a clinical protocol developed with our inpatient pharmacists. | 94 |
| Total | 94 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
| Overall Study | Discharged before 3rd enoxaparin dose | 16 |
| Overall Study | Lost to Follow-up | 3 |
Baseline characteristics
| Characteristic | Enoxaparin Metabolism |
|---|---|
| Age, Continuous | 52.6 years |
| Body Mass Index | 28.6 kg/m^2 |
| Caprini Score | 7 scores on a scale |
| Creatinine | 0.82 mg/dL |
| Current smoker | 14 Participants |
| Gross weight | 184 lbs |
| Length of chemoprophylaxis | 10.3 days |
| Length of hospital stay | 7.6 days |
| Length of operation | 281 minutes |
| Location of primary operation Back including pressure ulcers | 26 Participants |
| Location of primary operation Breast | 29 Participants |
| Location of primary operation Chest, nonbreast | 5 Participants |
| Location of primary operation Head and neck | 2 Participants |
| Location of primary operation Lower extremity | 30 Participants |
| Location of primary operation Upper extremity | 2 Participants |
| Number of patients receiving treatment for Diabetes | 8 Participants |
| Race/Ethnicity, Customized Ethnicity African American | 1 Participants |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 9 Participants |
| Race/Ethnicity, Customized Ethnicity Native American or Alaskan Native | 4 Participants |
| Race/Ethnicity, Customized Ethnicity Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Ethnicity White | 79 Participants |
| Region of Enrollment United States | 94 participants |
| Sex: Female, Male Female | 51 Participants |
| Sex: Female, Male Male | 43 Participants |
| Total body surface area surgically injured | 6.1 percentage of total body surface area |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 110 |
| other Total, other adverse events | 8 / 110 |
| serious Total, serious adverse events | 2 / 110 |
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: Bleeding events are reported for the 94 who were not discharged prior to the third Enoxaparin dose. Because two bleeding events occurred prior to the drawing of labs, they cannot be classified into low vs. in-range/high enoxaparin levels. Because of this, reporting on bleeding events is reported across the whole study population and not by arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low aFXa Level | Number of Participants With Bleeding Events | 3 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: Patients with out-of-range levels or missing levels were dropped from relevant analyses. Of the 89 participants who completed the study, 88 had peak steady-state anti-factor Xa levels to be analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low aFXa Level | Number of Participants With Venous Thromboembolism Events | 5 Participants |
| In-Range or High aFXa Level | Number of Participants With Venous Thromboembolism Events | 0 Participants |