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

NCT ID: NCT01014403

Last Updated: 2021-01-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-30
• Study Completion Date: 2011-05-31

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.

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.

Conditions

Venous Thromboembolism; Traumatic Brain Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

enoxaparin 30 mg SQ q12 hours

Enoxaparin started at 24 hours post-injury and continued until 96 hours post-injury.

Group Type: EXPERIMENTAL

enoxaparin

Intervention Type: DRUG

Enoxaparin 30 mg sq q 12 hours

placebo

vehicle administered sq q 12 hours

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

vehicle

Interventions

enoxaparin

Enoxaparin 30 mg sq q 12 hours

Intervention Type: DRUG

placebo

vehicle

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Herb A Phelan, MD

Role: PRINCIPAL_INVESTIGATOR

UT Southwestern Medical Center

Locations

UT-Southwestern Medical Center

Dallas, Texas, United States

East Texas Medical Center

Tyler, Texas, United States

Countries

United States

Other Identifiers

082009-026

Identifier Type: -

Identifier Source: org_study_id