Resuscitative Endocrinology:Single-dose Clinical Uses for Estrogen-Traumatic Brain Injury

NCT00973674 | Completed Phase 2 Results DMC

• 1 other identifier: RESCUE-TBI
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Traumatic Brain Injury

Outcome Measures

Primary Outcomes (1)

• Percent Passing the Galveston Orientation Amnesia Test (GOAT) Within 28 Days Post Injury

  The GOAT is a measure of early cognitive recovery following a severe traumatic injury. The score is determined after examination by health professionals with respect to orientation to person, place and time. On a scale 0 to 100, 76-100 represents normal recovery. The trial measures the percentage of patients who pass the Galveston Orientation Amnesia Test (GOAT) within 28 days post injury.

  28 Days

Secondary Outcomes (3)

• 28-day Mortality

  28 Days

• 6-month Glasgow Outcomes Scale- Extended (GOSE) Score

  Up to 6 months post-injury

• Acute Respiratory Distress Syndrome (ARDS) Free Survival

  Days 0-28

Study Arms (2)

Premarin IV

EXPERIMENTAL

Patients randomized to receive a single dose of 0.5 mg/kg Premarin® IV

Drug: Premarin IV

Placebo

PLACEBO COMPARATOR

Patients randomized to receive a single dose of placebo IV. Due of the faint yellow color of the reconstituted Premarin®, the placebo dose will be prepared with 0.14 ml of Vial 1 of Infuvite Adult Multivitamin and 14 ml of sterile water to generate a similar color and volume. This aliquot will be used only for those study patients who are randomized to the placebo arm. The placebo volume will be approximately equal to the volume which the patient would have received had the patient been randomized to the Premarin arm Considering the small amount of IV multivitamin needed for fluid tinting, it is not expected that the IV multivitamin will have any effect on patients with traumatic brain injury.

Drug: Placebo

Interventions

Premarin IV DRUG

One time dose of Premarin IV

Also known as: IV Estrogen

Premarin IV

Placebo DRUG

One time dose of Placebo

Also known as: Infivite Multivitamin

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Suspected blunt head injury
• Estimated age of 18 - 50 years
• Estimated time to study drug administration \< 2 hours post-trauma
• 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.
• Systolic blood pressure \> 90 mm Hg
• 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

You may not qualify if:

• Legal Do Not Resuscitate (DNR) orders in place prior to randomization.
• Known incarcerated individuals
• Status epilepticus prior to study drug administration
• Penetrating head trauma
• Estimated time to study drug administration \> 2 hours post-trauma
• Injury time unknown
• Cardiopulmonary Resuscitation (CPR) prior to study drug administration
• Severe hypothermia (suspected T \<28C)
• Drowning or asphyxia due to hanging
• Burns TBSA \> 20% in adults
• Systolic blood pressure \< or = 90 mm Hg
• Known indication for IV estrogen
• Known contraindication for estrogen (male sex is NOT a contraindication)
• Sustained pulse oximeter \< 90
• Recognized spinal cord injury prior to study drug administration

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• University of Washington: collaborator
• Resuscitation Outcomes Consortium: collaborator

Study Sites (2)

Parkland Hospital

Dallas, Texas, 75235, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

MeSH Terms

Conditions

Brain Injuries, Traumatic

Interventions

Estrogens

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Results Point of Contact

• Title: Scott Emerson, PhD
• Organization: University of Washington

semerson@uw.edu

206-616-6678

Study Officials

• Jane G Wigginton, MD

  UT Southwestern Medical Center Dallas

  PRINCIPAL INVESTIGATOR

• Schmickers Rob

  University of Washington

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2009
• First Posted: September 9, 2009
• Study Start: July 1, 2009
• Primary Completion: January 1, 2012
• Study Completion: May 1, 2012
• Last Updated: November 12, 2019
• Results First Posted: November 12, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)