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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Enoxaparin metabolism | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Enoxaparin | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 90 days |
| Number of Participants With Bleeding Events | Bleeding events requiring alteration in the course of care within 90 days of surgery | 90 days |
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Inclusion Criteria:
Inclusion criteria will include:
Exclusion Criteria:
Exclusion criteria will include:
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| Name | Affiliation | Role |
|---|---|---|
| Christopher Puccini, MD | University of Utah | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Utah | Salt Lake City | Utah | 84132 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38957026 | Derived | Paolini G, Firmani G, Sorotos M, Ninkovic M, Santanelli di Pompeo F. European guidelines on peri-operative venous thromboembolism prophylaxis: first update.: Chapter 8: Plastic surgery. Eur J Anaesthesiol. 2024 Aug 1;41(8):598-603. doi: 10.1097/EJA.0000000000001998. Epub 2024 Jul 10. No abstract available. | |
| 33086312 | Derived |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The sixteen participants that were discharged before the third enoxaparin dose were excluded from the analysis.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | 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. | Posted | Count of Participants | Participants | 90 days |
|
90 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Death | General disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Deep venous thrombosis | Vascular disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Christopher J. Pannucci, M.D., M.S. | Division of Plastic Surgery, University of Utah | 801-581-7719 | christopher.pannucci@hsc.utah.edu |
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| ID | Term |
|---|---|
| D054556 | Venous Thromboembolism |
| D020246 | Venous Thrombosis |
| D011655 | Pulmonary Embolism |
| ID | Term |
|---|---|
| D013923 | Thromboembolism |
| D016769 | Embolism and Thrombosis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D017984 | Enoxaparin |
| ID | Term |
|---|---|
| D006495 | Heparin, Low-Molecular-Weight |
| D006493 | Heparin |
| D006025 | Glycosaminoglycans |
| D011134 | Polysaccharides |
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| Pannucci CJ, Fleming KI, Varghese TK Jr, Stringham J, Huang LC, Pickron TB, Prazak AM, Bertolaccini C, Momeni A. Low Anti-Factor Xa Level Predicts 90-Day Symptomatic Venous Thromboembolism in Surgical Patients Receiving Enoxaparin Prophylaxis: A Pooled Analysis of Eight Clinical Trials. Ann Surg. 2022 Dec 1;276(6):e682-e690. doi: 10.1097/SLA.0000000000004589. Epub 2020 Oct 19. |
| 29649055 | Derived | Pannucci CJ, Fleming KI, Agarwal J, Rockwell WB, Prazak AM, Momeni A. The Impact of Once- versus Twice-Daily Enoxaparin Prophylaxis on Risk for Venous Thromboembolism and Clinically Relevant Bleeding. Plast Reconstr Surg. 2018 Jul;142(1):239-249. doi: 10.1097/PRS.0000000000004517. |
| 29452956 | Derived | Pannucci CJ, Fleming KI. Comparison of face-to-face interaction and the electronic medical record for venous thromboembolism risk stratification using the 2005 Caprini score. J Vasc Surg Venous Lymphat Disord. 2018 May;6(3):304-311. doi: 10.1016/j.jvsv.2017.10.016. Epub 2018 Feb 13. |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Body Mass Index | Mean | Full Range | kg/m^2 |
|
| Gross weight | Mean | Full Range | lbs |
|
| Number of patients receiving treatment for Diabetes | Count of Participants | Participants |
|
| Creatinine | Mean | Full Range | mg/dL |
|
| Current smoker | Count of Participants | Participants |
|
| Caprini Score | The Caprini risk score is a risk assessment tool for the occurrence of venous thromboembolism (VTE) among surgical patients. The Caprini risk score includes 40 factors, each ascribed points ranging from 1 to 5. The Caprini score is calculated by adding the scores of all factors present in the patient. The minimum possible score is 0. The maximum score for men is 85. The maximum score for women is 88. The Caprini score is interpreted in the following way: Score 0-1: Low risk of VTE Score 2: Moderate of VTE Score 3-4: High risk of VTE Score ≥ 5: Highest risk for VTE | Median | Full Range | scores on a scale |
|
| Location of primary operation | Count of Participants | Participants |
|
| Length of operation | Mean | Full Range | minutes |
|
| Total body surface area surgically injured | Mean | Full Range | percentage of total body surface area |
|
| Length of hospital stay | Mean | Full Range | days |
|
| Length of chemoprophylaxis | Mean | Full Range | days |
|
|
|
| Primary | Number of Participants With Bleeding Events | Bleeding events requiring alteration in the course of care within 90 days of surgery | 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. | Posted | Count of Participants | Participants | 90 days |
|
|
|
| 2 |
| 110 |
| 2 |
| 110 |
| 8 |
| 110 |
| Pulmonary Embolism | Vascular disorders | Non-systematic Assessment |
|
| Bleeding | Vascular disorders | Non-systematic Assessment | Bleeding events changing the course of care |
|
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| D013927 |
| Thrombosis |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D004617 | Embolism |
| D002241 |
| Carbohydrates |