Resuscitative Endocrinology:Single-dose Clinical Uses for Estrogen-Traumatic Brain Injury
Condition: Traumatic Brain Injury
MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Wounds and Injuries
Intervention: Premarin IV; Placebo
Intervention description: One time dose of Premarin IV; One time dose of Placebo
Intervention MeSH terms: Estrogens; Estrogens, Conjugated (USP)
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: No

Summary:

      Each year in the United States alone, a third of a million persons are hospitalized for
      traumatic brain injury (TBI), of whom approximately 1/4 die. Most are less than 30 years of
      age. Not only are the health care costs staggering for both initial care and rehabilitation,
      but the societal loss in terms of economic impact reaches into the billions of dollars
      annually in the U.S. alone. Despite advances in neurosurgical interventions and intensive
      care management, many survivors do not fully recover. A significant cause of this mortality
      and morbidity is thought due to potentially preventable secondary injury, namely oxidant
      injury, inflammation, and apoptosis in the penumbra (the area of brain surrounding the
      primary lesion, which is at-risk, but potentially salvageable), beginning in the first few
      hours after the severe traumatic event.

      Despite the current bleak outlook for many of these patients, a series of animal
      investigations have uncovered a promising solution to the problem of the secondary injury
      seen in severe TBI and other similar processes, namely the early administration of estrogen,
      a strong anti-oxidant, anti-inflammatory and anti-apoptotic compound. Based on these
      encouraging results from animal studies, the investigators hypothesize that early
      administration of IV Premarin® in patients with severe TBI will safely reduce secondary brain
      injury, improve neurological outcomes, and improve survival.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Suspected blunt head injury

          2. Estimated age of 18 - 50 years

          3. Estimated time to study drug administration < 2 hours post-trauma

          4. Glasgow Come Scale (GCS) score of between 3 and 8 prior to intubation and/or sedation,
             due to difficulty of patient's cooperation in assessment after these interventions.

          5. Systolic blood pressure > 90 mm Hg

          6. Receiving medical treatment in the Emergency Department (ED) of Parkland Hospital, or
             Baylor University Medical Center Emergency Department, Level I Trauma Centers in
             Dallas,Texas

        Exclusion Criteria:

          1. Legal Do Not Resuscitate (DNR) orders in place prior to randomization.

          2. Known incarcerated individuals

          3. Status epilepticus prior to study drug administration

          4. Penetrating head trauma

          5. Estimated time to study drug administration > 2 hours post-trauma

          6. Injury time unknown

          7. Cardiopulmonary Resuscitation (CPR) prior to study drug administration

          8. Severe hypothermia (suspected T <28C)

          9. Drowning or asphyxia due to hanging

         10. Burns TBSA > 20% in adults

         11. Known inclusion in another interventional trial related to this traumatic event prior
             to randomization

         12. Systolic blood pressure < or = 90 mm Hg

         13. Known indication for IV estrogen

         14. Known contraindication for estrogen (male sex is NOT a contraindication)

         15. Sustained pulse oximeter < 90

         16. Recognized spinal cord injury prior to study drug administration