Resuscitative Endocrinology: Single-dose Clinical Uses for Estrogen-Traumatic Hemorrhagic Shock (RESCUE - Shock)

Phase 2

Completed

Brief Summary: Based on encouraging results from animal studies, the investigators hypothesize that early administration of IV Premarin® in patients with hemorrhagic shock will safely reduce secondary injury, and improve survival.

Detailed Description: Annually in the United States, approximately 30 million people require treatment for traumatic injuries in emergency departments. Two million of these patients require hospitalization, with several hundred thousand ultimately dying, often due to extreme blood loss. Importantly, these traumatic injuries are the leading cause of death and disability for children and young adults under the age of 44, with the total cost of trauma in the U.S. approaching $260 billion each year.

Despite advances in pre-hospital care, early resuscitation, surgical interventions and intensive care monitoring aimed at the primary traumatic injury, many survivors never recover. A significant cause of this mortality and morbidity is thought due to potentially preventable secondary injury, namely oxidant injury, inflammation, and apoptosis beginning in the first few hours after the severe traumatic event.

In spite of 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 hemorrhagic shock and other similar processes, namely the early administration of estrogen, a strong anti-oxidant, anti-inflammatory and anti-apoptotic compound.

Based on encouraging results from animal studies, the investigators hypothesize that early administration of IV Premarin® in patients with hemorrhagic shock will safely reduce secondary injury, and improve survival.

Recruitment & Eligibility

Inclusion Criteria

Age≥ 18 yrs or < 50 yrs
Blunt or penetrating trauma leading to presumed hemorrhagic shock
Pre-hospital or ED systolic blood pressure < 90
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

Those who would receive the study drug > 120 minutes after the traumatic event
Time of injury is unknown
Known indication for IV estrogen
Known contraindication for estrogen
Estimated age <18 or > 50 years
Cardiopulmonary Resuscitation (CPR) prior to randomization
Known incarceration
Severe hypothermia (suspected T < 28° C)
Drowning or asphyxia due to hanging
Burns total body surface area (TBSA) > 20%
Isolated penetrating injury to the head
Known inclusion in another interventional trial related to this traumatic event prior to randomization
Known legal do not resuscitate (DNR) orders in place prior to randomization
Recognized spinal cord injury prior to study drug administration

Arm && Interventions

Group	Intervention	Description
Premarin IV	Premarin IV	Patients who were randomized to receive a single dose of 0.5 mg/kg Premarin® IV.
Placebo	Placebo	Patients who were randomized to receive a single dose of 0.5 mg/kg placebo. 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 hemorrhagic shock.

Primary Outcome Measures

Name	Time	Method
Survival	28 Days	Survival is defined as the number of patients who were discharged from the hospital alive prior to 28 days post injury or the number of patients still alive in the hospital 28 days post injury. The trial examines the rate of enrolled patients on each arm who survived to 28 days.

Secondary Outcome Measures

Name	Time	Method
Acute Respiratory Distress Syndrome (ARDS) Free Survival	28 days	ARDS is a life-threatening condition characterized by inflammation of the lungs. The trial measures the number of days alive and without ARDS within 28 days post injury. Patients who die within 28 days are given value of 0, similarly, patients who live 28 days but have ARDS for all 28 days. A higher score (greater days) indicates better prognosis. Exudative stage is 0-6 days, proliferative stage is 7-10 days, Fibrotic stage is \>10-14 days.