The Clinical Utility of Thrombelastography in Guiding Prophylaxis of Venous Thromboembolism Following Trauma (VTEPX)

This study has been completed.
Sponsor:
Collaborator:
Eisai Inc.
Information provided by (Responsible Party):
Ernest Moore, Denver Health and Hospital Authority
ClinicalTrials.gov Identifier:
NCT01050153
First received: January 13, 2010
Last updated: March 25, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention
Venous Thromboembolism
Drug: Dalteparin sodium
Drug: Dalteparin sodium/aspirin

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by Denver Health and Hospital Authority:

Primary Outcome Measures:
  • Hypercoagulability [ Time Frame: Study day five. ] [ Designated as safety issue: Yes ]
    To determine the incidence of, and to characterize, hypercoagulability in a sample of trauma patients admitted to the SICU at DHMC using TEG and conventional clinical coagulation testing (APTT, INR), antithrombin III levels and protein C activity. Hypercoagulability is defined as TEG parameter G (clot strength) >10.9.

  • Incidence of VTE [ Time Frame: Day 28 or discharge, whichever comes first. ] [ Designated as safety issue: Yes ]
    The incidence and nature of hypercoagulability and the incidence of deep vein thrombosis and pulmonary embolism in each randomized group and in the subgroup receiving anti-platelet therapy in addition to Fragmin (descriptive analysis only)


Secondary Outcome Measures:
  • TEG Parameters [ Time Frame: Study day five. ] [ Designated as safety issue: Yes ]

    R is a reaction time. The time from the start of a sample run until the first significant levels of detectable clot formation (amplitude = 2 mm in the TEG tracing).

    Rf is a difference in reaction time between Fragmin-active and Fragmin-neutralized samples.

    Achievement of a certain clot strength K is a measure of the time from R until a fixed level of clot strength is reached (amplitude = 20 mm).

    Angle or α measures the rapidity of fibrin build-up and cross-linking (clot strengthening). This most represents fibrinogen level. Angle relates to K, since both are a function of the rate of clot formation.

    MA, or Maximum Amplitude, is a direct function of the maximum clot strength. In tests where platelets are part of the clot, this parameter most reflects platelet function/aggregation. Clot strength is the result of two components - the modest contribution of fibrin and the much more significant contribution of the platelets.


  • Conventional Coagulation Testing Parameters [ Time Frame: Study day five. ] [ Designated as safety issue: Yes ]
    Plasma based conventional coagulation testing parameters - INR

  • Platelet Count [ Time Frame: Study day five. ] [ Designated as safety issue: Yes ]
    Platelet count measured by CBC test

  • TEG Parameters [ Time Frame: Study day five. ] [ Designated as safety issue: Yes ]

    Shear elastic modulus strength (SEMS). The MA parameter can be transformed into the actual measure of clot strength (G) using the formula below, and is measured in dyn/cm2 divided by 1000 (displayed in the software as Kd/sc).

    The absolute SEMS of the sample can be calculated from MA as follows:

    G = (5000MA/(100-MA))/1000 An amplitude of 50 mm corresponds to a SEMS of 5000 dyn/cm2. An increase in MA from 50 mm to 67 mm is equivalent to a two-fold increase in the SEMS. The G parameter not only provides a measurement of clot firmness in force units, but also is more indicative of small changes in the clot strength or clot breakdown than is the amplitude in mm because it is an exponential reflection of MA.


  • Conventional Coagulation Testing Parameters [ Time Frame: Study day five. ] [ Designated as safety issue: Yes ]
    Plasma based conventional coagulation testing parameters - Anti Xa

  • Conventional Coagulation Testing Parameters [ Time Frame: Study day five. ] [ Designated as safety issue: Yes ]
    Plasma based conventional coagulation testing parameters - Fibrinogen

  • Conventional Coagulation Testing Parameters [ Time Frame: Study day five. ] [ Designated as safety issue: Yes ]
    Plasma based conventional coagulation testing parameters - Anti-thrombin III

  • Conventional Coagulation Testing Parameters [ Time Frame: Study day five. ] [ Designated as safety issue: Yes ]
    Plasma based conventional coagulation testing parameters - Protein C


Enrollment: 50
Study Start Date: March 2010
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Control (standard of care)
Dalteparin sodium 5000IU subcutaneously daily
Drug: Dalteparin sodium
Dalteparin sodium injection 5000IU subcutaneously daily until fully ambulatory
Other Name: Dalteparin sodium (Fragmin)
Experimental: TEG-guided thromboprophylaxis
Dalteparin sodium plus/minus anti-platelet medication (aspirin) per a TEG-guided algorithm
Drug: Dalteparin sodium/aspirin
Dalteparin sodium (2500-10,000IU sc daily), aspirin (81-325mg daily) po.
Other Name: dalteparin sodium (Fragmin)

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

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

  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: NCT01050153

Locations
United States, Colorado
Denver Health Medical Center
Denver, Colorado, United States, 80204
Sponsors and Collaborators
Denver Health and Hospital Authority
Eisai Inc.
Investigators
Principal Investigator: Ernest E. Moore Jr, M.D. Chief, Department of Surgery and Trauma Services , Denver Health Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: Ernest Moore, Chief, Department of Surgery and Trauma Services Rocky Mountain Regional Trauma Center, Denver Health and Hospital Authority
ClinicalTrials.gov Identifier: NCT01050153     History of Changes
Other Study ID Numbers: COMIRB # 09-0753
Study First Received: January 13, 2010
Results First Received: August 14, 2013
Last Updated: March 25, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Denver Health and Hospital Authority:
Prevention of venous thromboembolism

Additional relevant MeSH terms:
Venous Thromboembolism
Venous Thrombosis
Thromboembolism
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Thrombosis
Aspirin
Heparin, Low-Molecular-Weight
Dalteparin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 29, 2014