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| Name | Class |
|---|---|
| United States Air Force | FED |
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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.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Serum anti-Xa >= 0.1 IU/mL | No Intervention | Patients with serum anti-Xa level >= 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours | |
| Anti-Xa <0.1 IU/mL:enoxaparin 40 mg q12h | Active Comparator | Patients with serum anti-Xa level < 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours who then receive enoxaparin 40 mg every 12 hours. If repeat steady state trough anti-Xa is subtherapeutic, dose will be increased to enoxaparin 50 mg every 12 hours. |
|
| Anti-Xa <0.1 IU/mL:enoxaparin 30 mg q8h | Active Comparator | Patients with serum anti-Xa level < 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours who then receive enoxaparin 30 mg every eight hours |
|
| Serum anti-Xa < 0.1 IU/mL | No Intervention | Patients with serum anti-Xa level < 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Enoxaparin 40 mg q12h | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | After third dose of enoxaparin 30mg q12h, which will typically be on Day 2 of enoxaparin |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Molly Droege, PharmD | UC Health - University of Cincinnati Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Cincinnati Medical Center | Cincinnati | Ohio | 45216 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33978907 | Result | Droege ME, Droege CA, Philpott CD, Webb ML, Ernst NE, Athota K, Wakefield D, Dowd JR, Gomaa D, Robinson BHR, Hanseman D, Elterman J, Mueller EW. Impact of antithrombin III and enoxaparin dosage adjustment on prophylactic anti-Xa concentrations in trauma patients at high risk for venous thromboembolism: a randomized pilot trial. J Thromb Thrombolysis. 2021 Nov;52(4):1117-1128. doi: 10.1007/s11239-021-02478-4. Epub 2021 May 12. |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Control Group | Patients with serum anti-Xa level >= 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours n = 51 4 with AT-III not collected so 47 included in primary outcome analysis |
| FG001 | Intervention Group | Patients with serum anti-Xa < 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours n = 52 1 patient withdrew consent; 2 patients did not have AT-III collected. 49 total included in primary outcome analyses. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary Endpoint |
| |||||||||||||
| Intervention Group: Randomization |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | Intervention: Serum Anti-Xa < 0.1 IU/mL |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| 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 | 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 | Posted | Median | Inter-Quartile Range | Percent AT-III activity (%) | After third dose of enoxaparin 30mg q12h, which will typically be on Day 2 of enoxaparin |
|
During patient enrollment up to 28 days, while inpatient
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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 | Control Group | Patients with serum anti-Xa level >= 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours n = 51 4 with AT-III not collected so 47 included in primary outcome analysis |
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Underpowered; See full results and manuscript listed in citation section.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Molly Droege, PharmD | UC Health - University of Cincinnati Medical Center | 513-584-2126 | molly.droege@uchealth.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | Nov 30, 2016 | Sep 27, 2021 | Prot_SAP_ICF_000.pdf |
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| ID | Term |
|---|---|
| D014947 | Wounds and Injuries |
| D054556 | Venous Thromboembolism |
| 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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|
| Enoxaparin 30 mg q8h | Drug | Patients receive enoxaparin 30 mg every 8 hours. |
|
|
| NOT COMPLETED |
|
Patients with serum anti-Xa level < 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
Patients with serum anti-Xa < 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours
n = 52
1 patient withdrew consent; 2 patients did not have AT-III collected. 49 total included in primary outcome analyses.
|
|
|
| 0 |
| 51 |
| 0 |
| 51 |
| 0 |
| 51 |
| EG001 | Intervention Group | Patients with serum anti-Xa < 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours n = 52 1 patient withdrew consent; 2 patients did not have AT-III collected. 49 total included in primary outcome analyses. | 0 | 52 | 0 | 51 | 0 | 51 |
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| D002241 |
| Carbohydrates |