Delayed Versus Early Enoxaparin Prophylaxis After Traumatic Brain Injury (TBI) (DEEP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01014403
Recruitment Status : Unknown
Verified November 2009 by University of Texas Southwestern Medical Center.
Recruitment status was:  Recruiting
First Posted : November 17, 2009
Last Update Posted : November 17, 2009
Information provided by:
University of Texas Southwestern Medical Center

Brief Summary:
Brain injured patients are at high risk for forming blood clots in the legs and lungs. For non-brain injured trauma patients, we decrease the chances of these blood clots forming by placing the patients on a low dose of the blood thinner enoxaparin. Starting patients with a brain injury on the blood thinner is problematic, however, as this can theoretically cause the brain injury to worsen. Trauma surgeons wait a variable period of time before starting this blood thinner because waiting too long can result in the formation of these blood clots in the legs and lungs. Previous research has shown that some brain injuries which are of lower severity can have enoxaparin started at 24 hours after injury if the brain injury is stable on a repeated computed tomography (CT) scan of the head. This is a pilot study designed to look at the rates of worsening of brain injury if the low dose blood thinner is started at 24 versus 96 hours post-injury.

Condition or disease Intervention/treatment Phase
Venous Thromboembolism Traumatic Brain Injury Drug: enoxaparin Drug: placebo Phase 1

Detailed Description:

We propose to conduct a placebo-controlled non-inferiority pilot study to evaluate the rate of worsening of intracranial injury patterns after initiation of enoxaparin in TBI patients. Patient enrollment will occur at ETMC, blinded re-reading of CTs will occur at PMH, and administrative/analytical support will occur at UTSW. The study design will be a double-blind, randomized controlled trial in the ETMC Surgical Intensive Care Unit (SICU) consisting of 40 patients per arm. The decision for 80 patients was resource-based, as this is a pilot study. Further, we anticipate the need to contact 3 patients in order to obtain 1 successful recruitment.

Each arm will consist of low-risk TBI patients (defined as patients with a subdural or epidural hematoma < 8mm, intraparenchymal contusion < 2 cm, and/or single contusion per lobe) who have had a CT scan of the head without contrast at 24 hours post-injury which documents a stable injury pattern. The severity of neurologic deficit will have no bearing on their suitability for participation, and will not be considered in inclusion/exclusion criteria. After documentation of a stable intracranial injury pattern at this time interval, patients will be randomized to receive either enoxaparin 30 mg SQ every 12 hours or placebo with each regimen being initiated at 24 hours post-injury. A follow-up CT scan of the brain without contrast will be obtained on all patients 48 hours post-injury (and 24 hours after the initiation of enoxaparin/placebo). An additional CT scan of the brain without contrast will be obtained on any patient who experiences an abrupt change in neurologic exam at any time between the initiation of enoxaparin/placebo and the end of the study's interventional period at 96 hours post-injury (this time frame was chosen as it is the earliest time point at which there is universal agreement among both of our group's practitioners that enoxaparin use is safe from the risks of TBI expansion). Any patient with a worsened CT scan will have their investigational treatment discontinued at that time. At 96 hours post-injury, the interventional portion of the study will end, data collection for the primary endpoint will cease, and all patients will be placed on enoxaparin for the remainder of their hospital stay as per local standards of care. Patient participation in the study will last from the time of injury to 96 hours post-injury for the interventional part of the study, and from 96 hours post-injury until discharge from ETMC for the observational portion. While this latter time frame is obviously extremely variable, it averages approximately one to two weeks. During both the interventional and observational time periods, patients will have Duplex ultrasonography of the lower extremities performed for an edematous extremity, CT-angiography of the chest for unexplained hypoxia or tachycardia, and ventilation-perfusion scanning for suspicion of PE in the presence of a contraindication to IV contrast.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Delayed vs Early Enoxaparin Prophylaxis (DEEP) Study After Traumatic Brain Injury: A Randomized, Double-Blinded, Placebo Controlled Pilot Trial
Study Start Date : November 2009
Estimated Primary Completion Date : November 2010
Estimated Study Completion Date : November 2010

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: enoxaparin 30 mg SQ q12 hours
Enoxaparin started at 24 hours post-injury and continued until 96 hours post-injury.
Drug: enoxaparin
Enoxaparin 30 mg sq q 12 hours
Drug: placebo
Placebo Comparator: placebo
vehicle administered sq q 12 hours
Drug: placebo

Primary Outcome Measures :
  1. Worsening of TBI hemorrhage pattern on any scheduled or PRN CT scans after the initiation of treatment [ Time Frame: prior to discharge ]

Secondary Outcome Measures :
  1. extracranial hemorrhagic complications [ Time Frame: prior to discharge ]
  2. Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE) [ Time Frame: prior to discharge ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

1. Male and female patients admitted to the ETMC SICU with TBI who speak English or Spanish.

Exclusion Criteria:

  1. Epidural or subdural hematoma > 8mm.
  2. Intraparenchymal contusion >2 cm
  3. Multiple contusions w/in one lobe
  4. Subarachnoid hemorrhage in basilar or supracellar cistern and positive CTA
  5. Increased TBI on 24 hr post-injury CT
  6. Spinal canal hematoma
  7. Nonoperative mgmt of American Association for the Surgery of Trauma (AAST) Grade IV or higher organ injury
  8. Gastrointestinal hemorrhage
  9. Ongoing bleeding from a pelvic fracture
  10. Anticipated open reduction of long bone or pelvic fracture within study period.
  11. Intracranial pressure (ICP) >20 mmHg
  12. Coagulopathy consisting of International Normalized Ratio (INR)>1.5 or platelet count <50,000
  13. Expect brain death/discharge in 48 hrs
  14. Pre-existing dialysis dependence
  15. Documented DVT at time of admission
  16. Prisoners
  17. Pregnancy
  18. Age <18 years
  19. Terminally ill patients
  20. Anticoagulant use at time of injury
  21. Inability to gain consent from patient or legal next-of-kin in instance of TBI, intoxication, or psychiatric diagnoses
  22. Documented history of heparin allergy
  23. Initial head CT >6 hours post-injury

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01014403

Contact: Herb A Phelan, MD 214-648-6841
Contact: Joseph P Minei, MD 214-648-7295

United States, Texas
UT-Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
East Texas Medical Center Recruiting
Tyler, Texas, United States, 75701
Contact: Scott Norwood, MD    903-535-2902   
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Principal Investigator: Herb A Phelan, MD UT Southwestern Medical Center

Responsible Party: Herb Phelan, MD, FACS, UT-Southwestern Medical Center Division of Burns/Trauma/Critical Care Identifier: NCT01014403     History of Changes
Other Study ID Numbers: 082009-026
First Posted: November 17, 2009    Key Record Dates
Last Update Posted: November 17, 2009
Last Verified: November 2009

Keywords provided by University of Texas Southwestern Medical Center:
venous thromboembolism
traumatic brain injury
Venous thromboembolism prophylaxis after traumatic brain injury

Additional relevant MeSH terms:
Wounds and Injuries
Brain Injuries
Brain Injuries, Traumatic
Venous Thromboembolism
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases