Clinical Trial Details
— Status: Enrolling by invitation
Administrative data
| NCT number |
NCT06025162 |
| Other study ID # |
028.PHA.2022.D |
| Secondary ID |
|
| Status |
Enrolling by invitation |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
July 21, 2023 |
| Est. completion date |
August 31, 2024 |
Study information
| Verified date |
September 2023 |
| Source |
Methodist Health System |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Venous thromboembolism (VTE) causes up to 100,000 deaths annually. Between 10%-30% of
patients die within one month of VTE diagnosis, while survivors remain at increased risk for
VTE recurrence or other complications like post-thrombotic syndrome or chronic pulmonary
hypertension in the following decade. Trauma patients have many risk factors that predispose
them to a VTE. During the first 48 hours after blunt trauma, patients are prothrombotic due
to the release of procoagulant factors, have excessive thrombin generation due to extensive
tissue and vascular injury, and have reduced circulation of endogenous anticoagulants like
protein C.
Description:
Trauma patients have many risk factors that predispose them to a VTE. During the first 48
hours after blunt trauma, patients are prothrombotic due to the release of procoagulant
factors, have excessive thrombin generation due to extensive tissue and vascular injury, and
have reduced circulation of endogenous anticoagulants like protein C. Trauma patients are
immobile for prolonged periods of time due to frequent surgical intervention and extended
sedation. Even when administered chemoprophylaxis, up to 15% of trauma patients develop
thromboses. Given the high rates of thromboses, one study validated certain risk factors for
VTE among trauma patients. This study categorized patients as high-risk or very high-risk of
VTE based on patient-specific factors. High-risk factors for VTE included a history of VTE,
repair or ligation of major venous injury, an abbreviated injury scale (AIS) >2 for the head,
a Glasgow coma Scale (GCS) score <8 for >4 hours after trauma, and age ≥60 years. Very
high-risk factors for VTE consist of complex lower extremity fractures, pelvic fractures,
spinal cord injury with associated para- or quadriplegia, and age ≥75 years. The 2020 Western
Trauma Association guidelines recommend initiation of VTE prophylaxis with enoxaparin within
24 hours of admission in trauma patients, with special consideration for patients with active
bleeding, solid organ injury, traumatic brain injury (TBI), or spinal cord injury. Several
studies support this recommendation and correlate delays in VTE prophylaxis initiation and
interruption in therapy with increased risk of VTE.
Recent evidence also highlights that the standard trauma VTE dosing strategy of 30 mg of
enoxaparin twice daily often fails to reach adequate target anti-Xa levels in trauma
patients. Thus, consideration of 0.5 mg/kg enoxaparin twice daily with adjustments based on
anti-Xa levels may be considered in patients at highest risk of VTE. This strategy may be
associated with improved outcomes while mitigating adverse effects like clinically
significant bleeding.
Despite these recommendations, providers may choose to delay initiation of VTE prophylaxis
due to a patient's apparent bleeding risk. Trauma-induced coagulopathy is present in 20%-25%
of patients and is associated with a higher incidence of bleeding, increased transfusion
requirements, and elevated risk of multi-organ failure versus patients without this
coagulopathy. Additionally, chemical VTE prophylaxis with anticoagulants like LMWH may
increase bleeding possibility, especially in patients that are at risk for emergent surgical
intervention. Even so, current evidence supports that early initiation of VTE prophylaxis in
high-risk patients, as benefit outweighs bleed risk.
Special trauma populations like TBI, spinal cord injury, and solid organ injury have been the
focus of recent studies evaluating bleeding risk after initiation of VTE prophylaxis. In one
study, TBI patients were at a significantly increased risk for VTE and substantial delays in
VTE prophylaxis initiation (7 days vs 1.5 days) versus non-TBI patients. Concern for
intracranial hemorrhage (ICH) progression was most likely found to cause delays in VTE
prophylaxis in this high-risk population despite the overall low incidence of this finding.15
In patients with intracranial bleeding, two studies identified that initiation of VTE
prophylaxis 24 hours after stable computerized tomography (CT) imaging did not increase risk
of ICH progression while decreasing overall incidence of VTE. For patients with blunt solid
organ injury, initiation of VTE prophylaxis within 48 hours of injury was not associated with
an escalation in bleeding events, but delaying prophylaxis beyond 72 hours correlated with in
increased risk for VTE. VTE prophylaxis initiation within 48 hours of non-operative spinal
cord injury was also found to significantly reduce VTE incidence versus initiation beyond 48
hours.
In 2020, Methodist Dallas Medical Center's (MDMC's) pharmacy department developed a guideline
for VTE prophylaxis in trauma patients. This document was designed to improve patient
outcomes by providing evidence to assist providers when initiating patients on chemical VTE
prophylaxis and support the safe and efficacious use of weight-based VTE prophylaxis regimens
in patients at high-risk of VTE. The guideline's algorithm first recommends assessing for
contraindications for chemical VTE prophylaxis (like ongoing hemorrhagic shock). After
assessing contraindications and creatinine clearance, the document provided guidance on LMWH
dosing strategies, suggested patient populations for weight-based prophylaxis regimens, and
recommended timeframes for initiation of VTE prophylaxis based on injury type. Patient
outcomes have not been assessed since the implementation of MDMC-specific VTE prophylaxis
trauma guidelines.
