Trial Outcomes & Findings for The Use of Fondaparinux in Preventing Thromboembolism in High Risk Trauma Patients (NCT NCT00531843)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

105 participants

Primary outcome timeframe

within 3 weeks post injury

Results posted on

2013-12-24

Participant Flow

During a 6-month period, consecutive adults presenting to one Level I urban trauma center were screened for eligibility, enrolled and assigned to a treatment category using previously-developed clinical guidelines.

Of 105 enrolled participants, 18 were excluded from analysis (13 discharged or transferred prior to second venous ultrasonography; 4 received non-study DVT prophylaxis; 1 had a known protein-C deficiency).

Participant milestones

Participant milestones
Measure	Fondaparinux Sodium Patients at high risk or very high risk for venous thromboembolism received fondaparinux 2.5mg via subcutaneous administration (SubQ) daily, with (very high risk) or without (high risk) mechanical compression upon admission or by 3rd day after injury.	No Fondaparinux Patients at high risk or very high risk for venous thromboembolism AND contraindication to anticoagulant administration received mechanical compression, with (very high risk) or without (high risk) possible temporary inferior vena cava (IVC) filter (prn as determined by caregiver).
Overall Study STARTED	81	6
Overall Study COMPLETED	81	6
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Fondaparinux Sodium n=81 Participants Patients at high risk or very high risk for venous thromboembolism received fondaparinux 2.5mg SubQ daily, with (very high risk) or without (high risk) mechanical compression upon admission or by 3rd day after injury.	No Fondaparinux n=6 Participants Patients at high risk or very high risk for venous thromboembolism AND contraindication to anticoagulant administration received mechanical compression, with (very high risk) or without (high risk) possible temporary IVC filter (prn as determined by caregiver).	Total n=87 Participants Total of all reporting groups
Age Continuous	43.1 years STANDARD_DEVIATION 19.3 • n=5 Participants	56.8 years STANDARD_DEVIATION 20.9 • n=7 Participants	44.3 years STANDARD_DEVIATION 19.7 • n=5 Participants
Sex: Female, Male Female	21 Participants n=5 Participants	1 Participants n=7 Participants	22 Participants n=5 Participants
Sex: Female, Male Male	60 Participants n=5 Participants	5 Participants n=7 Participants	65 Participants n=5 Participants
Region of Enrollment United States	81 participants n=5 Participants	6 participants n=7 Participants	87 participants n=5 Participants

PRIMARY outcome

Timeframe: within 3 weeks post injury

Population: Of 11 patients with initial contraindication to anticoagulation, 5 were cleared by the treating physicians to receive fondaparinux within 3 days of injury, and 6 were not.

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.

Outcome measures

Outcome measures
Measure	Fondaparinux Sodium n=81 Participants Patients at high risk or very high risk for venous thromboembolism received fondaparinux 2.5mg SubQ daily, with (very high risk) or without (high risk) mechanical compression upon admission or by 3rd day after injury.	No Fondaparinux n=6 Participants Patients at high risk or very high risk for venous thromboembolism AND contraindication to anticoagulant administration received mechanical compression, with (very high risk) or without (high risk) possible temporary IVC filter (prn as determined by caregiver).
Presence of Deep Vein Thrombosis (DVT) or Pulmonary Embolus (PE) DVT	2 participants	2 participants
Presence of Deep Vein Thrombosis (DVT) or Pulmonary Embolus (PE) DVT after fondaparinux	1 participants	NA participants This arm/group did not receive Fondaparinux.
Presence of Deep Vein Thrombosis (DVT) or Pulmonary Embolus (PE) PE	0 participants	0 participants

SECONDARY outcome

Timeframe: Day 3

Population: Serum samples were obtained from 63 representative patients from our study who received Fondaparinux and compared against normative values from normal volunteers supplied by our sponsor.

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.

Outcome measures

Outcome measures
Measure	Fondaparinux Sodium n=63 Participants Patients at high risk or very high risk for venous thromboembolism received fondaparinux 2.5mg SubQ daily, with (very high risk) or without (high risk) mechanical compression upon admission or by 3rd day after injury.	No Fondaparinux Patients at high risk or very high risk for venous thromboembolism AND contraindication to anticoagulant administration received mechanical compression, with (very high risk) or without (high risk) possible temporary IVC filter (prn as determined by caregiver).
Normal Trough and Peak Fondaparinux Concentration Trough values outside normative range	0 Participants	—
Normal Trough and Peak Fondaparinux Concentration Peak values outside normative range	0 Participants	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Fondaparinux Sodium n=81 Participants Patients at high risk or very high risk for venous thromboembolism received fondaparinux 2.5mg SubQ daily, with (very high risk) or without (high risk) mechanical compression upon admission or by 3rd day after injury.	No Fondaparinux Patients at high risk or very high risk for venous thromboembolism AND contraindication to anticoagulant administration received mechanical compression, with (very high risk) or without (high risk) possible temporary IVC filter (prn as determined by caregiver).
Increased Bleeding Attributed to Fondaparinux	0 participants	—

Adverse Events

Fondaparinux Sodium

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

No Fondaparinux

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Fondaparinux Sodium n=81 participants at risk Patients at high risk or very high risk for venous thromboembolism received fondaparinux 2.5mg SubQ daily, with (very high risk) or without (high risk) mechanical compression upon admission or by 3rd day after injury.	No Fondaparinux n=6 participants at risk Patients at high risk or very high risk for venous thromboembolism AND contraindication to anticoagulant administration received mechanical compression, with (very high risk) or without (high risk) possible temporary IVC filter (prn as determined by caregiver).
Blood and lymphatic system disorders Drop in hematocrit	16.0% 13/81 • Number of events 13 • 3 weeks post-injury This study did not record adverse events that were related to the severity of participants' trauma unless assessed for potential attribution to study participation	0.00% 0/6 • 3 weeks post-injury This study did not record adverse events that were related to the severity of participants' trauma unless assessed for potential attribution to study participation
Vascular disorders DVT	2.5% 2/81 • Number of events 2 • 3 weeks post-injury This study did not record adverse events that were related to the severity of participants' trauma unless assessed for potential attribution to study participation	33.3% 2/6 • Number of events 2 • 3 weeks post-injury This study did not record adverse events that were related to the severity of participants' trauma unless assessed for potential attribution to study participation
Vascular disorders Superficial nonoccluding clots	4.9% 4/81 • Number of events 4 • 3 weeks post-injury This study did not record adverse events that were related to the severity of participants' trauma unless assessed for potential attribution to study participation	0.00% 0/6 • 3 weeks post-injury This study did not record adverse events that were related to the severity of participants' trauma unless assessed for potential attribution to study participation

Additional Information

M. Margaret Knudson, MD

UCSF/SF General Hospital

Phone: 415.205.4623

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place