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

NCT00531843 | Completed Phase 2 Results

• 1 other identifier: H6693-30799-01
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

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.

Conditions

Venous Thromboembolism

Keywords

deep vein thrombosis; venous thromboembolism; pulmonary embolism

Outcome Measures

Primary Outcomes (1)

• Presence of Deep Vein Thrombosis (DVT) or Pulmonary Embolus (PE)

  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.

  within 3 weeks post injury

Secondary Outcomes (2)

• Normal Trough and Peak Fondaparinux Concentration

  Day 3

• Increased Bleeding Attributed to Fondaparinux

  3 weeks post injury

Study Arms (4)

1A

EXPERIMENTAL

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

1B

ACTIVE COMPARATOR

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

2A

EXPERIMENTAL

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

2B

ACTIVE COMPARATOR

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

Interventions

fondaparinux sodium DRUG

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.

Also known as: Arixtra

1A; 2A

sequential compression devices DEVICE

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.

Also known as: Arixtra

1B; 2B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mary Knudson, M.D.: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

San Francisco General Hospital

San Francisco, California, 94143, United States

Location

Related Publications (16)

• Agnelli G, Bergqvist D, Cohen AT, Gallus AS, Gent M; PEGASUS investigators. Randomized clinical trial of postoperative fondaparinux versus perioperative dalteparin for prevention of venous thromboembolism in high-risk abdominal surgery. Br J Surg. 2005 Oct;92(10):1212-20. doi: 10.1002/bjs.5154.

  PMID: 16175516 BACKGROUND

• Geerts WH, Jay RM, Code KI, Chen E, Szalai JP, Saibil EA, Hamilton PA. A comparison of low-dose heparin with low-molecular-weight heparin as prophylaxis against venous thromboembolism after major trauma. N Engl J Med. 1996 Sep 5;335(10):701-7. doi: 10.1056/NEJM199609053351003.

  PMID: 8703169 BACKGROUND

• Velmahos GC. Posttraumatic thromboprophylaxis revisited: an argument against the current methods of DVT and PE prophylaxis after injury. World J Surg. 2006 Apr;30(4):483-7. doi: 10.1007/s00268-005-0427-9.

  PMID: 16568226 BACKGROUND

• Hill AB, Garber B, Dervin G, Howard A. Heparin prophylaxis for deep venous thrombosis in a patient with multiple injuries: an evidence-based approach to a clinical problem. Can J Surg. 2002 Aug;45(4):282-7.

  PMID: 12174986 BACKGROUND

• Geerts WH, Pineo GF, Heit JA, Bergqvist D, Lassen MR, Colwell CW, Ray JG. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep;126(3 Suppl):338S-400S. doi: 10.1378/chest.126.3_suppl.338S.

  PMID: 15383478 BACKGROUND

• Turpie AG, Bauer KA, Eriksson BI, Lassen MR; PENTATHALON 2000 Study Steering Committee. Postoperative fondaparinux versus postoperative enoxaparin for prevention of venous thromboembolism after elective hip-replacement surgery: a randomised double-blind trial. Lancet. 2002 May 18;359(9319):1721-6. doi: 10.1016/S0140-6736(02)08648-8.

  PMID: 12049860 BACKGROUND

• Kudsk KA, Fabian TC, Baum S, Gold RE, Mangiante E, Voeller G. Silent deep vein thrombosis in immobilized multiple trauma patients. Am J Surg. 1989 Dec;158(6):515-9. doi: 10.1016/0002-9610(89)90182-7.

  PMID: 2589580 BACKGROUND

• Knudson MM, Ikossi DG. Venous thromboembolism after trauma. Curr Opin Crit Care. 2004 Dec;10(6):539-48. doi: 10.1097/01.ccx.0000144941.09650.9f.

  PMID: 15616398 BACKGROUND

• Donat F, Duret JP, Santoni A, Cariou R, Necciari J, Magnani H, de Greef R. The pharmacokinetics of fondaparinux sodium in healthy volunteers. Clin Pharmacokinet. 2002;41 Suppl 2:1-9. doi: 10.2165/00003088-200241002-00001.

  PMID: 12383039 BACKGROUND

• Knudson MM, Ikossi DG, Khaw L, Morabito D, Speetzen LS. Thromboembolism after trauma: an analysis of 1602 episodes from the American College of Surgeons National Trauma Data Bank. Ann Surg. 2004 Sep;240(3):490-6; discussion 496-8. doi: 10.1097/01.sla.0000137138.40116.6c.

  PMID: 15319720 BACKGROUND

• Eriksson BI, Bauer KA, Lassen MR, Turpie AG; Steering Committee of the Pentasaccharide in Hip-Fracture Surgery Study. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after hip-fracture surgery. N Engl J Med. 2001 Nov 1;345(18):1298-304. doi: 10.1056/NEJMoa011100.

  PMID: 11794148 BACKGROUND

• Bauer KA, Eriksson BI, Lassen MR, Turpie AG; Steering Committee of the Pentasaccharide in Major Knee Surgery Study. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after elective major knee surgery. N Engl J Med. 2001 Nov 1;345(18):1305-10. doi: 10.1056/NEJMoa011099.

  PMID: 11794149 BACKGROUND

• Geerts WH, Code KI, Jay RM, Chen E, Szalai JP. A prospective study of venous thromboembolism after major trauma. N Engl J Med. 1994 Dec 15;331(24):1601-6. doi: 10.1056/NEJM199412153312401.

  PMID: 7969340 BACKGROUND

• Allen TL, Carter JL, Morris BJ, Harker CP, Stevens MH. Retrievable vena cava filters in trauma patients for high-risk prophylaxis and prevention of pulmonary embolism. Am J Surg. 2005 Jun;189(6):656-61. doi: 10.1016/j.amjsurg.2005.03.003.

  PMID: 15910715 BACKGROUND

• Cohen AT, Davidson BL, Gallus AS, Lassen MR, Prins MH, Tomkowski W, Turpie AG, Egberts JF, Lensing AW; ARTEMIS Investigators. Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial. BMJ. 2006 Feb 11;332(7537):325-9. doi: 10.1136/bmj.38733.466748.7C. Epub 2006 Jan 26.

  PMID: 16439370 BACKGROUND

• Lu JP, Knudson MM, Bir N, Kallet R, Atkinson K. Fondaparinux for prevention of venous thromboembolism in high-risk trauma patients: a pilot study. J Am Coll Surg. 2009 Nov;209(5):589-94. doi: 10.1016/j.jamcollsurg.2009.08.001. Epub 2009 Sep 11.

  PMID: 19854398 RESULT

MeSH Terms

Conditions

Venous Thromboembolism; Venous Thrombosis; Pulmonary Embolism

Interventions

Fondaparinux

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Thrombosis; Lung Diseases; Respiratory Tract Diseases; Embolism

Intervention Hierarchy (Ancestors)

Oligosaccharides; Polysaccharides; Carbohydrates

Results Point of Contact

• Title: M. Margaret Knudson, MD
• Organization: UCSF/SF General Hospital

pknudson@sfghsurg.ucsf.edu

415.205.4623

Study Officials

• M. Margaret Knudson, MD

  The University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 17, 2007
• First Posted: September 19, 2007
• Study Start: December 1, 2007
• Primary Completion: June 1, 2008
• Study Completion: June 1, 2008
• Last Updated: December 24, 2013
• Results First Posted: December 24, 2013

Record last verified: 2013-10

Locations

US (1)