Blood Clot, Trauma
Conditions
Keywords
Trauma, Blood clot, Venous Thromboembolism, Pulmonary Embolism, Deep Vein Thrombosis, Thromboprophylaxis, Blood clot prevention, trauma patients
Brief summary
The purpose of this study is to compare aspirin versus low-molecular weight heparin (LMWH) (Enoxaparin) as a thromboprophylaxis in patients who sustain a fracture.
Detailed description
Patients who sustain orthopaedic trauma are at an increased risk of venous thromboembolism (VTE), including fatal pulmonary embolism (PE). Current guidelines recommend low-molecular-weight heparin (LMWH) for VTE prophylaxis in orthopaedic trauma patients. However, emerging literature in total joint arthroplasty patients suggests the potential clinical benefits of VTE prophylaxis with aspirin. This trial aims to determine if aspirin is non-inferior to LMWH for thromboprophylaxis in fracture patients.
Interventions
DRUGAcetylsalicylic acid
The Aspirin intervention will be 81 mg enteral (by mouth, feeding tube or rectal) twice a day with no variation in dosing allowed.
The LMWH intervention will be 30 mg enoxaparin subcutaneous (under the skin) twice a day with variations in dosing allowed, per the standard of care at sites, as needed for patients who are very obese or exhibit renal dysfunction.
Sponsors
Patient-Centered Outcomes Research Institute
Major Extremity Trauma Research Consortium
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who have a planned operative or non-operative pelvis or acetabular fracture, or any operative extremity fracture proximal to the metatarsals or carpals. * Patients at increased risk of blood clot(s) from their orthopaedic injury(ies) and will receive prophylactic blood thinner regimen per standard of care. * Patients 18 years or older.
Exclusion criteria
* Patients who present to the hospital more than 48 hours post injury * Patients who received more than 2 doses of LMWH or aspirin for initial VTE prophylaxis * Patients on long term blood thinners (other than low-dose aspirin or platelet inhibitors such as Plavix or Aggrenox) * Patients who have had a VTE within the last 6 months * Patients on therapeutic (as opposed to prophylactic) blood thinners for an acute issue at the time of admission * Patients who have a newly diagnosed indication for therapeutic blood thinners (for example vascular injury) that will require therapeutic anticoagulation for more than one week * Patients who cannot receive either of the study medications due to an allergy (history of heparin induced thrombocytopenia, allergy to aspirin, or NSAIDs) or other medical contraindication to blood thinners * Patients who are on higher dose aspirin (\>81 mg once a day or higher) for medical reasons or who will be treated with higher dose aspirin * Patients with underlying chronic clotting disorders (i.e. Factor V Leiden, hyperhomocysteinemia, Protein C and S deficiency) that require full dose anticoagulation or are a contraindication to venous thromboembolism chemoprophylaxis * Patients with end stage renal disease or impaired creatinine clearance \<30 ml/min at time of randomization(note: creatinine clearance does not need to be documented if prescribing physician would order medication without test as SOC) * Pregnant or lactating patients * Prisoners * Patients who do not speak either English or Spanish * Patients who are likely to have severe problems maintaining follow-up * Patients, based upon the clinical judgment of the treating clinician, NOT equally suited for treatment with either aspirin or low-molecular-weight heparin * Patients may be excluded for other reasons at the discretion of the treating physician; the reason for exclusion must be documented on the screening form * Patients who have a known COVID-19 diagnosis prior to fracture treatment or within 3 months of the index fracture
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With All-cause Mortality | 90 days | Death from any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Non-fatal Pulmonary Embolism | 90 days | — |
| Deep Vein Thrombosis | 90 days | — |
| Number of Participants With Cause-specific Death | 90 days | Cause specific death. Some participants are reported twice if reason for death met more than one category. |
| Wound Complication | 90 days | — |
| Deep Surgical Site Infection | 90 days | — |
| Bleeding Complication | 90 days | — |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Low Molecular Weight Heparin (LMWH)-Enoxaparin Injection of 30 mg enoxaparin, twice a day via injection
Low Molecular Weight Heparin (LMWH): The LMWH intervention will be 30 mg enoxaparin subcutaneous (under the skin) twice a day with variations in dosing allowed, per the standard of care at sites, as needed for patients who are very obese or exhibit renal dysfunction. | 6,110 |
| Acetylsalicylic Acid (ASA)-Aspirin Enteral ingestion or administration of 81 mg ASA, twice a day
Acetylsalicylic acid: The Aspirin intervention will be 81 mg enteral (by mouth, feeding tube or rectal) twice a day with no variation in dosing allowed. | 6,101 |
| Total | 12,211 |
Baseline characteristics
| Characteristic | Total | Acetylsalicylic Acid (ASA)-Aspirin | Low Molecular Weight Heparin (LMWH)-Enoxaparin |
|---|---|---|---|
| Age, Continuous | 44.6 years STANDARD_DEVIATION 17.8 | 44.5 years STANDARD_DEVIATION 18 | 44.7 years STANDARD_DEVIATION 17.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1510 Participants | 774 Participants | 736 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10701 Participants | 5327 Participants | 5374 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Injury Severity Score | 9 Scores on a scale | 9 Scores on a scale | 9 Scores on a scale |
| Median body-mass index | 27.4 kg/m^2 | 27.1 kg/m^2 | 27.5 kg/m^2 |
| Race (NIH/OMB) American Indian or Alaska Native | 99 Participants | 55 Participants | 44 Participants |
| Race (NIH/OMB) Asian | 161 Participants | 82 Participants | 79 Participants |
| Race (NIH/OMB) Black or African American | 2507 Participants | 1264 Participants | 1243 Participants |
| Race (NIH/OMB) More than one race | 129 Participants | 61 Participants | 68 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 25 Participants | 11 Participants | 14 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 935 Participants | 470 Participants | 465 Participants |
| Race (NIH/OMB) White | 8355 Participants | 4158 Participants | 4197 Participants |
| Sex: Female, Male Female | 4610 Participants | 2269 Participants | 2341 Participants |
| Sex: Female, Male Male | 7601 Participants | 3832 Participants | 3769 Participants |
| Without Health Insurance | 2643 Participants | 1355 Participants | 1288 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 45 / 6,110 | 47 / 6,101 |
| other Total, other adverse events | 879 / 6,110 | 840 / 6,101 |
| serious Total, serious adverse events | 260 / 6,110 | 324 / 6,101 |
Outcome results
Primary
Number of Participants With All-cause Mortality
Death from any cause
Time frame: 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Molecular Weight Heparin (LMWH)-Enoxaparin | Number of Participants With All-cause Mortality | 45 Participants |
| Acetylsalicylic Acid (ASA)-Aspirin | Number of Participants With All-cause Mortality | 47 Participants |
Secondary
Bleeding Complication
Time frame: 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Molecular Weight Heparin (LMWH)-Enoxaparin | Bleeding Complication | 869 Participants |
| Acetylsalicylic Acid (ASA)-Aspirin | Bleeding Complication | 834 Participants |
Secondary
Deep Surgical Site Infection
Time frame: 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Molecular Weight Heparin (LMWH)-Enoxaparin | Deep Surgical Site Infection | 93 Participants |
| Acetylsalicylic Acid (ASA)-Aspirin | Deep Surgical Site Infection | 103 Participants |
Secondary
Deep Vein Thrombosis
Time frame: 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Molecular Weight Heparin (LMWH)-Enoxaparin | Deep Vein Thrombosis | 103 Participants |
| Acetylsalicylic Acid (ASA)-Aspirin | Deep Vein Thrombosis | 151 Participants |
Secondary
Non-fatal Pulmonary Embolism
Time frame: 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Molecular Weight Heparin (LMWH)-Enoxaparin | Non-fatal Pulmonary Embolism | 90 Participants |
| Acetylsalicylic Acid (ASA)-Aspirin | Non-fatal Pulmonary Embolism | 90 Participants |
Secondary
Number of Participants With Cause-specific Death
Cause specific death. Some participants are reported twice if reason for death met more than one category.
Time frame: 90 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Low Molecular Weight Heparin (LMWH)-Enoxaparin | Number of Participants With Cause-specific Death | Death related to PE | 5 Participants |
| Low Molecular Weight Heparin (LMWH)-Enoxaparin | Number of Participants With Cause-specific Death | Death possibly related to PE *includes Death related to PE participants | 14 Participants |
| Low Molecular Weight Heparin (LMWH)-Enoxaparin | Number of Participants With Cause-specific Death | Death unlikely to be related to PE | 31 Participants |
| Acetylsalicylic Acid (ASA)-Aspirin | Number of Participants With Cause-specific Death | Death related to PE | 4 Participants |
| Acetylsalicylic Acid (ASA)-Aspirin | Number of Participants With Cause-specific Death | Death possibly related to PE *includes Death related to PE participants | 18 Participants |
| Acetylsalicylic Acid (ASA)-Aspirin | Number of Participants With Cause-specific Death | Death unlikely to be related to PE | 29 Participants |
Secondary
Wound Complication
Time frame: 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Molecular Weight Heparin (LMWH)-Enoxaparin | Wound Complication | 14 Participants |
| Acetylsalicylic Acid (ASA)-Aspirin | Wound Complication | 8 Participants |