Deep Venous Thrombosis, Pulmonary Embolus, Reconstructive Surgery, Venous Thromboembolism
Conditions
Brief summary
Plastic and reconstructive surgeons consistently create large, raw surfaces as part of their operative procedures. Thus, plastic & reconstructive surgery patients are among those at highest risk for anticoagulant-associated bleeding adverse drug events (ADEs). This study seeks to optimize both the safety and effectiveness of post-operative enoxaparin by comparing aFXa levels, bleeding events, and VTE events among plastic & reconstructive surgery patients randomized to receive two different enoxaparin dose regimens.
Detailed description
Plastic and reconstructive surgeons consistently create large, raw surfaces as part of their operative procedures. Thus, plastic & reconstructive surgery patients are among those at highest risk for anticoagulant-associated bleeding adverse drug events (ADEs). Our preliminary data has shown that a fixed, or one size fits all dose of enoxaparin, an anticoagulant, can allow a high proportion of patients to have appropriately thinned blood, measured by anti-Factor Xa (aFXa) levels. Patients with adequate aFXa levels are known to have significantly decreased venous thromboembolism risk (VTE), which is desirable. However, 30% of patients who receive fixed dose enoxaparin have blood that is too thin. Patients who are over-anticoagulated are significantly more likely to have ADEs including bleeding requiring return to the operating room, need for blood transfusion, or death. The optimal way to dose enoxaparin to minimize ADEs remains unknown. This study seeks to optimize both the safety and effectiveness of post-operative enoxaparin by comparing aFXa levels, bleeding events, and VTE events among plastic & reconstructive surgery patients randomized to receive two different enoxaparin dose regimens.
Interventions
DRUGFixed dose
Participants will receive 40 mg enoxaparin twice daily
DRUGVariable dose
Participants will receive 0.5mg/kg enoxaparin twice daily
Sponsors
Stanford University
University of Utah
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Patients will be randomized into one of two groups (enoxaparin 40mg twice daily or enoxaparin 0.5mg/kg twice daily, rounded to the nearest milligram).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* receiving plastic and reconstructive surgery under general anesthesis * Expected post-operative stay of 2 days or more
Exclusion criteria
* Contraindication to use of enoxaparin * intracranial bleeding/stroke * Hematoma or bleeding disorder * Heparin-induced thrmbocytopenia positive * Creatinine clearance less than or equal to 30 mL/min * Serum creatinine greater than 1.6 mg/dL * epidural anesthesia * patients placed on non-enoxaparin chemoprophylaxis regimens * gross weight exceeding 150kg
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Avoidance of Under-anticoagulation (Peak aFXa <0.2 IU/mL) | Four hours following third enoxaparin dose | Avoidance of under-anticoagulation (peak aFXa \<0.2 IU/mL) |
| Avoidance of Over-anticoagulation (Peak aFXa >0.4 IU/mL) | Four hours following third enoxaparin dose | Avoidance of over-anticoagulation (peak aFXa \>0.4 IU/mL) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage 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 |
| Percentage of Patients 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 |
|---|---|
| Fixed Dose Participants will receive 40 mg enoxaparin twice daily
Fixed dose: Participants will receive 40 mg enoxaparin twice daily | 151 |
| Variable Dose Participants will receive 0.5mg/kg enoxaparin twice daily
Variable dose: Participants will receive 0.5mg/kg enoxaparin twice daily | 144 |
| Total | 295 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Bled requiring enoxaparin cessation | 4 | 2 |
| Overall Study | developed acute renal failure | 0 | 1 |
| Overall Study | Discharged prior to Xa level | 12 | 8 |
| Overall Study | Initiated heparin infusion on floor | 1 | 1 |
| Overall Study | Medication distribution error | 1 | 0 |
| Overall Study | Refused study medication | 3 | 0 |
| Overall Study | Required epidural placement | 1 | 0 |
| Overall Study | Unexpected return to OR | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Fixed Dose | Variable Dose | Total |
|---|---|---|---|
| Age, Continuous | 49.0 years STANDARD_DEVIATION 15.6 | 52.7 years STANDARD_DEVIATION 14.8 | 50.8 years STANDARD_DEVIATION 15.3 |
| Race/Ethnicity, Customized African American | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 11 Participants | 8 Participants | 19 Participants |
| Race/Ethnicity, Customized Native American/Alaskan Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 137 Participants | 135 Participants | 272 Participants |
| Region of Enrollment United States | 151 participants | 144 participants | 295 participants |
| Sex/Gender, Customized Female | 81 Participants | 70 Participants | 151 Participants |
| Sex/Gender, Customized Male | 70 Participants | 74 Participants | 144 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 151 | 0 / 144 |
| other Total, other adverse events | 0 / 151 | 0 / 144 |
| serious Total, serious adverse events | 0 / 151 | 0 / 144 |
Outcome results
Primary
Avoidance of Over-anticoagulation (Peak aFXa >0.4 IU/mL)
Avoidance of over-anticoagulation (peak aFXa \>0.4 IU/mL)
Time frame: Four hours following third enoxaparin dose
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fixed Dose | Avoidance of Over-anticoagulation (Peak aFXa >0.4 IU/mL) | 82.2 percentage of participants |
| Variable Dose | Avoidance of Over-anticoagulation (Peak aFXa >0.4 IU/mL) | 90.6 percentage of participants |
Primary
Avoidance of Under-anticoagulation (Peak aFXa <0.2 IU/mL)
Avoidance of under-anticoagulation (peak aFXa \<0.2 IU/mL)
Time frame: Four hours following third enoxaparin dose
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fixed Dose | Avoidance of Under-anticoagulation (Peak aFXa <0.2 IU/mL) | 76.6 percentage of participants |
| Variable Dose | Avoidance of Under-anticoagulation (Peak aFXa <0.2 IU/mL) | 79.9 percentage of participants |
Secondary
Percentage 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fixed Dose | Percentage of Participants With Venous Thromboembolism Events | 0.66 percentage of patients |
| Variable Dose | Percentage of Participants With Venous Thromboembolism Events | 0.69 percentage of patients |
Secondary
Percentage of Patients With Bleeding Events
Bleeding events requiring alteration in the course of care within 90 days of surgery
Time frame: 90 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fixed Dose | Percentage of Patients With Bleeding Events | 6.0 percentage of patients |
| Variable Dose | Percentage of Patients With Bleeding Events | 8.3 percentage of patients |