Clinical trial NCT01050153: The Clinical Utility of Thrombelastography in Guiding Prophylaxis of Venous Thromboembolism Following Trauma
Official title: An Evaluation of the Clinical Utility of Thrombelastography (TEG) in Guiding Low Molecular Weight Heparin (LMWH) and Antiplatelet Prophylaxis of Venous Thromboembolism (VTE) Following Trauma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Venous Thromboembolism
Keywords: Prevention of venous thromboembolism
Lead sponsor: Denver Health and Hospital Authority
Sponsor class: OTHER
Collaborators: name: Eisai Inc.
First posted: 2010-01-15
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study plans to learn more about how to prevent blood clots in the veins of your extremities. You are at risk of forming these clots after a major injury and when you have had surgery and are hospitalized on bed rest.

Usually, patients in the SICU at Denver Health who are at risk for blood clots receive preventative treatment with a FDA-approved medicine called Fragmin. Fragmin is intended to prevent blood clots from forming but, with the way it is generally used, some patients may still develop blood clots. All patients treated with Fragmin to prevent blood clots at Denver Health, currently receive the same Fragmin dose. This treatment is called the "standard of care".

So far, in the US, there has not been a commonly available test that can tell us:

* if the standard dose of Fragmin is enough to prevent blood clots for everyone, or
* if different patients need different doses, or
* if other blood clot preventing medicines, that work in a different way, should be used in addition to Fragmin.

The ability of your blood to clot and the strength of the clot formed can be described by a FDA-approved blood test called thrombelastography, referred to as TEG. TEG may provide us with answers to each of the questions above. Our preliminary data indicate that it is helpful in assessing both clotting and bleeding tendencies and may prove useful in guiding treatment for the prevention of blood clots.

The aim of this study is to determine if a treatment plan using Fragmin, and, if indicated, one or two additional FDA-approved medicines called anti-platelet drugs, guided by the results of TEG testing, may be better at preventing blood clots than our current standard of care.

Detailed description: This preliminary/pilot study involves a prospective, randomized, open-label, parallel group comparison of Denver Health's current standard of care for prevention of venous thromboembolism (VTE), commonly known as blood clots, using LMWH (Fragmin) 5000IU subcutaneously daily, with a thrombelastography (TEG)-guided, algorithm-based, individualized regimen of LMWH (Fragmin) plus/minus anti-platelet therapy (aspirin) guided by platelet mapping, in patients admitted to the SICU following trauma.

Approximately 50 trauma patients for whom prevention of VTE with LMWH is indicated, will be enrolled over a six month period.

The specific aims of this study are as follows:

1. To determine the incidence of, and to characterize, hypercoagulability using TEG and conventional clinical coagulation testing (APTT, INR), Antithrombin III levels and Protein C activity.
2. In the group of patients receiving LMWH (Fragmin) therapy alone for prevention of VTE:

   1. to assess the anticoagulant effect of standard LMWH (Fragmin) dosing (5000IU subcutaneously once daily) using TEG and Anti-Factor Xa level measurement, and
   2. to determine the extent of correlation of relevant TEG parameters with measured Anti-Factor Xa levels (U/ml).
3. To assess whether TEG is a useful clinical tool for monitoring and optimizing prophylactic LMWH (Fragmin) therapy and for identifying the need for anti-platelet therapy to minimize the risk of VTE in these patients.
4. To evaluate the clinical utility of platelet mapping for guiding anti-platelet therapy in those patients for whom it is indicated by TEG results.
5. To determine the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) in each randomized group and in the subgroup receiving anti-platelet therapy in addition to LMWH (Fragmin) for prevention of VTE.

The overall aim is to utilize the above data to evaluate a) the adequacy of our standard Fragmin dosing regimen (5000IU subcutaneously once daily) alone for prevention of VTE in our trauma/SICU patients, b) the need for anti-platelet agents in addition to LMWH (Fragmin) for prevention of VTE in our population, and c) to validate/further develop the TEG-guided algorithm for optimal prophylaxis of VTE using LMWH (Fragmin) plus/minus anti-platelet therapy guided by platelet mapping.

Eligibility criteria: Inclusion Criteria:

* age at least 18 years,
* blunt or penetrating trauma requiring admission to the SICU
* requirement for LMWH (Fragmin) therapy for prophylaxis of VTE as standard of care, and
* informed consent by patient, legally authorized representative or proxy decision maker (if patient incompetent to provide) obtained and documented.

Exclusion Criteria:

Presence of any of the following absolute contraindications to LMWH (Fragmin) therapy:

* known hypersensitivity to dalteparin sodium,
* known hypersensitivity to heparin or pork products,
* thrombocytopenia associated with positive tests for antiplatelet antibody in the presence of Fragmin,
* history of heparin-induced thrombocytopenia (HIT),
* chronic liver disease (bilirubin \>2 mg/dl) or kidney insufficiency (CrCl \<30mL/min),
* intravascular thrombolytic therapy within 24 hours,
* resuscitation that required massive transfusion (\>10 units RBC within 6 hours),
* ongoing resuscitation for hemorrhagic shock,
* known bleeding disorder or coagulopathy (INR \>2 not on warfarin),
* thrombocytopenia (platelets \<20K/uL),
* subdural or epidural hematoma.

Or

Presence of any of the following relative contraindications to LMWH (Fragmin) therapy:

* new intracranial lesions, neoplasms or monitoring devices,
* extravascular thrombolytic therapy,
* severe uncontrolled hypertension,
* arterial dissection
* recent (within 12 hours) intraocular surgery (prior or planned),
* recent (within 72 hours) intracranial or spine surgery (prior or planned),
* conditions associated with increased risk of hemorrhage, e.g. active gastrointestinal ulceration, angiodysplastic disease, gastrointestinal bleeding within the past six months, bacterial endocarditis, history of hemorrhagic stroke, diabetic retinopathy.

Or

Presence, or removal within the last 12 hours, of an indwelling epidural or spinal catheter, OR recent (within the last 12 hours) or planned neuraxial (spinal/epidural) anesthesia or spinal puncture.

Or

Per history taken from patient or family, concomitant or known use within one week prior to hospitalization, of drugs affecting hemostasis such as NSAIDS, platelet inhibitors or other anticoagulants, except as specified in this protocol.

Primary outcomes:
measure: Hypercoagulability
timeFrame: Study day five.
measure: Incidence of VTE
timeFrame: Day 28 or discharge, whichever comes first.
Secondary outcomes:
measure: TEG Parameters
timeFrame: Study day five.
measure: International Normalized Ratio (INR)
timeFrame: Study day five.
measure: Platelet Count
timeFrame: Study day five.
measure: TEG Parameters
timeFrame: Study day five.
measure: Conventional Coagulation Testing Parameters
timeFrame: Study day five.
measure: Conventional Coagulation Testing Parameters
timeFrame: Study day five.
measure: Conventional Coagulation Testing Parameters
timeFrame: Study day five.
measure: Conventional Coagulation Testing Parameters
timeFrame: Study day five.
Other outcomes:
Locations:
city: Denver
country: United States
facility: Denver Health Medical Center
state: Colorado
Study officials:
affiliation: Chief, Department of Surgery and Trauma Services , Denver Health Medical Center
name: Ernest E. Moore Jr, M.D.
role: PRINCIPAL_INVESTIGATOR
References: