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

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Mary Knudson, M.D., University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00531843
First received: September 17, 2007
Last updated: October 31, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Venous Thromboembolism
Drug: fondaparinux sodium
Device: sequential compression devices
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: The Use of Fondaparinux in Preventing Thromboembolism in High Risk Trauma Patients

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Presence of Deep Vein Thrombosis (DVT) or Pulmonary Embolus (PE) [ Time Frame: within 3 weeks post injury ] [ Designated as safety issue: Yes ]
    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:
  • Normal Trough and Peak Fondaparinux Concentration [ Time Frame: Day 3 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 3 weeks post injury ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 105
Study Start Date: December 2007
Study Completion Date: June 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1A
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.
Drug: fondaparinux sodium
fondaparinux 2.5mg SubQ daily for DVT prophylaxis to be started by treating physicians once deemed safe and to be discontinued once patient in discharged from the hospital or at discretion of treating physicians.
Other Name: Arixtra
Active Comparator: 1B
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.
Device: sequential compression devices
Sequential compression devices at all times during the patient's hospital admission will be used in patients who have a contraindication to pharmacologic DVT prophylaxis. This is already the current standard of care.
Other Name: Arixtra
Experimental: 2A
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.
Drug: fondaparinux sodium
fondaparinux 2.5mg SubQ daily for DVT prophylaxis to be started by treating physicians once deemed safe and to be discontinued once patient in discharged from the hospital or at discretion of treating physicians.
Other Name: Arixtra
Active Comparator: 2B
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).
Device: sequential compression devices
Sequential compression devices at all times during the patient's hospital admission will be used in patients who have a contraindication to pharmacologic DVT prophylaxis. This is already the current standard of care.
Other Name: Arixtra

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00531843

Locations
United States, California
San Francisco General Hospital
San Francisco, California, United States, 94143
Sponsors and Collaborators
Mary Knudson, M.D.
GlaxoSmithKline
Investigators
Principal Investigator: M. Margaret Knudson, MD The University of California, San Francisco
  More Information

Publications:

Responsible Party: Mary Knudson, M.D., Principal Investigator, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00531843     History of Changes
Other Study ID Numbers: H6693-30799-01
Study First Received: September 17, 2007
Results First Received: June 10, 2013
Last Updated: October 31, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, San Francisco:
deep vein thrombosis
venous thromboembolism
pulmonary embolism

Additional relevant MeSH terms:
Thromboembolism
Venous Thromboembolism
Venous Thrombosis
Cardiovascular Diseases
Embolism and Thrombosis
Thrombosis
Vascular Diseases
Fondaparinux
PENTA
Anticoagulants
Cardiovascular Agents
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014