The Use of Fondaparinux in Preventing Thromboembolism in High Risk Trauma Patients

Phase 2

Completed

Conditions: Venous Thromboembolism

Interventions: Device: sequential compression devices
Drug: fondaparinux sodium

Registration Number: NCT00531843

Lead Sponsor: Mary Knudson, M.D.

Brief Summary: Trauma patients are at high risk of developing deep vein thrombosis (DVT) and pulmonary embolism (PE). The incidence of DVT varies greatly from 5-63% among studies depending on patient's individual risk factors, modality of prophylaxis, and methods of detection. The incidence of PE may be as low (0.3-4.3%) but carries a mortality of 20-50% which makes prevention of DVT of the utmost importance. The current standard of care for DVT prophylaxis in the trauma patient with high risk of DVT is enoxaparin, a low molecular weight heparin, administered twice a day as long as anticoagulation in not contraindicated. Many studies have demonstrated its efficacy when compared to mechanical compression and to unfractionated heparin, however one of the most robust of these studies still reported an DVT incidence of 35% in patients treated with enoxaparin. Another drug, fondaparinux, is a selective factor Xa inhibitor that could offer added benefits over enoxaparin such as once daily dosing and a drastically reduced risk of heparin induced thrombocytopenia (HIT). Fondaparinux has been already be widely used in post-operative hip surgery and major knee surgery patients with good results. It has also been shown to be effective in DVT prophylaxis in patients who have had major abdominal surgery and also in acute medical patients. Fondaparinux has yet to be used in trauma patients. Trauma patients are a diverse and distinct population given the acuity of their injuries and their increased risk of bleeding who at this time still do not have a perfect method for DVT prophylaxis. We hypothesize that fondaparinux will be effective in decreasing the risk of DVT when used in the trauma patient population. This is a non randomized prospective cohort study designed to test the efficacy of fondaparinux in the prophylaxis of DVT and PE in trauma patients.

Detailed Description: Patients with trauma admitted to San Francisco General Hospital and qualify for the study will be assigned to +fondaparinux and no fondaparinux arms based on guidelines that were developed for and are considered the standard of care for the use of low molecular weight heparin in the same group of patients for the same indication. These guidelines will separate patients at risk for DVT into those that are high risk and very high risk. The primary efficacy outcome measures will be DVT and PE. Presence of DVT will be assessed with serial color flow duplex ultrasound during the patients in hospital stay at weekly intervals up to 3 weeks and when the patient has symptoms of DVT. PE will be diagnosed according to clinical suspicion by the patients treating physicians and subsequent imaging by CT. We plan on enrolling approximately 100 patients in the +fondaparinux and 100 patients in the no fondaparinux arm. We will compare both the incidence of DVT and PE in these groups and to the incidences in the literature and historical controls. A second aim of the study is to evaluate the adverse outcomes such as increased bleeding in patients who receive fondaparinux. A third and final aim of the study is to describe the effect of fondaparinux on antifactor Xa levels in trauma patients.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 105

Inclusion Criteria

Patients age ≥ 18 years old admitted to San Francisco General Hospital for injury with at least one risk factor for venous thromboembolism (VTE).

Risk factors are: Age ≥ 40 years, pelvic fracture, lower extremity fracture, spinal cord injury, shock or head injury, major operative procedure, mechanical ventilation > 3 days, venous injury

Exclusion Criteria

prisoners
pregnant patients
patients who are anticipated to have a < 5 day length of stay as determined by the admitting trauma surgeon
patients who decline to participate in the study

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1B	sequential compression devices	Patients at high risk for venous thromboembolism (criteria: age\>=40, pelvic fracture, lower extremity fracture, shock on presentation, spinal cord injury, head injury with AIS \>=3) who also have a contraindication to anticoagulant(enoxaparin)administration such as renal failure with creatine clearance \<30 mL/min, head injury with head AIS \>=3), uncontrolled hemorrhage, uncorrected coagulopathy, persistent thrombocytopenia. These patients will receive mechanical compression.
2B	sequential compression devices	Patients at very high risk for venous thromboembolism (criteria: major operative procedure, venous injury, ventilator days \>3, 2 or more high risk factors) who also have a contraindication to anticoagulant(enoxaparin)administration such as renal failure creatine clearance \<30 mL/min, head injury with head AIS \>=3), uncontrolled hemorrhage, uncorrected coagulopathy, persistent thrombocytopenia. These patients will receive mechanical compression and possibly temporary inferior vena cava (IVC) filter(as determined by the patient's care givers).
1A	fondaparinux sodium	Patients at high risk for venous thromboembolism (criteria: age\>=40, pelvic fracture, lower extremity fracture, shock on presentation, spinal cord injury, head injury with Abbreviated Injury Scale (AIS) \>=3). These patients will receive fondaparinux 2.5mg via subcutaneous administration (SubQ) daily.
2A	fondaparinux sodium	Patients at very high risk for venous thromboembolism (criteria: major operative procedure, venous injury, ventilator days \>3, 2 or more high risk factors). These patients will receive fondaparinux 2.5mg SubQ daily and mechanical compression.

Primary Outcome Measures

Name	Time	Method
Presence of Deep Vein Thrombosis (DVT) or Pulmonary Embolus (PE)	within 3 weeks post injury	Color-flow duplex venous ultrasonography examinations of upper and lower extremities were performed within 48 hours of injury, and then weekly until discharge or 3 weeks. DVT was defined as any clot occurring in the subclavian, iliac, femoral, or popliteal location. Patients were examined daily for clinical signs and symptoms of venous thromboembolism (VTE) and PE. Small, nonocclusive clots discovered in other locations were observed for progression on sequential ultrasonography examinations.

Secondary Outcome Measures

Name	Time	Method
Normal Trough and Peak Fondaparinux Concentration	Day 3	Serum samples were collected 30 minutes before (trough) and 2 hours after (peak) the third dose of fondaparinux. Normative data plots comparing study participants with healthy volunteers were supplied by the company outsourced to analyze samples.
Increased Bleeding Attributed to Fondaparinux	3 weeks post injury	Coagulopathic bleeding due to fondaparinux was suspected in patients requiring packed red cell transfusions after initiation of fondaparinux therapy only if the change in hematocrit prompting transfusion was not clinically commensurate with the degree of injuries that the patient had sustained (primarily orthopaedic) and/or the hematocrit did not respond appropriately post-transfusion.