Trial Outcomes & Findings for Resuscitative Endocrinology:Single-dose Clinical Uses for Estrogen-Traumatic Brain Injury (NCT NCT00973674)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

50 participants

Primary outcome timeframe

28 Days

Results posted on

2019-11-12

Participant Flow

Clinical sites enrolled men and women age 18 to 55 who experienced severe traumatic brain injury in the EMS setting between September 2009 and January 2012.

Participant milestones

Participant milestones
Measure	Premarin IV Patients randomized to receive a single dose of 0.5 mg/kg Premarin® IV Premarin IV: One time dose of Premarin IV	Placebo Patients randomized to receive a single dose of placebo IV. Due to 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. Placebo: One time dose of Placebo
Overall Study STARTED	24	26
Overall Study COMPLETED	22	26
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Premarin IV Patients randomized to receive a single dose of 0.5 mg/kg Premarin® IV Premarin IV: One time dose of Premarin IV	Placebo Patients randomized to receive a single dose of placebo IV. Due to 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. Placebo: One time dose of Placebo
Overall Study Protocol Violation	2	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Premarin IV n=22 Participants Patients randomized to receive a single dose of 0.5 mg/kg Premarin® IV Premarin IV: One time dose of Premarin IV	Placebo n=26 Participants 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. Placebo: One time dose of Placebo	Total n=48 Participants Total of all reporting groups
Age, Continuous	31.9 years n=5 Participants	34.3 years n=7 Participants	33.3 years n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	23 Participants n=7 Participants	42 Participants n=5 Participants
Region of Enrollment United States	22 participants n=5 Participants	26 participants n=7 Participants	48 participants n=5 Participants

PRIMARY outcome

Timeframe: 28 Days

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.

Outcome measures

Outcome measures
Measure	Premarin IV n=22 Participants Patients randomized to receive a single dose of 0.5 mg/kg Premarin® IV Premarin IV: One time dose of Premarin IV	Placebo n=26 Participants 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. Placebo: One time dose of Placebo
Percent Passing the Galveston Orientation Amnesia Test (GOAT) Within 28 Days Post Injury	12 Participants	14 Participants

SECONDARY outcome

Timeframe: 28 Days

Mortality is defined as the number of patients who died prior to 28 days post injury. Patients who are still in the hospital 28-days post injury are considered alive. The trial examines the rate of enrolled patients on each arm who died prior to 28 days post injury.

Outcome measures

Outcome measures
Measure	Premarin IV n=22 Participants Patients randomized to receive a single dose of 0.5 mg/kg Premarin® IV Premarin IV: One time dose of Premarin IV	Placebo n=26 Participants 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. Placebo: One time dose of Placebo
28-day Mortality	7 participants	2 participants

SECONDARY outcome

Timeframe: Up to 6 months post-injury

Population: The study specifically measures long-term GOSE, defined as post 6 months. Six month follow-up were not available for all patients and thus the lower sample size. As a secondary measure, missing values were not imputed.

The GOSE is a scale for functional outcome following a severe traumatic injury. The GOSE is an ordinal variable with the following categories: Dead, Vegetative State, Lower Severe Disability, Upper Severe Disability, Lower Moderate Disability, Upper Moderate Disability, Lower Good Recovery, and Upper Good Recovery. The GOSE score is determined by a structured interview with questions surrounding consciousness, independence inside and outside the home, social and leisure activities and return to normal life among others. A higher score is considered to be a better result. A lower score indicates a worse result. The scale is 1-8, level 1 minimum score, level 8 maximum score.

Outcome measures

Outcome measures
Measure	Premarin IV n=18 Participants Patients randomized to receive a single dose of 0.5 mg/kg Premarin® IV Premarin IV: One time dose of Premarin IV	Placebo n=22 Participants 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. Placebo: One time dose of Placebo
6-month Glasgow Outcomes Scale- Extended (GOSE) Score	4.00 units on a scale Standard Deviation 2.85	4.82 units on a scale Standard Deviation 2.58

SECONDARY outcome

Timeframe: Days 0-28

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 indicates better prognosis.

Outcome measures

Outcome measures
Measure	Premarin IV n=22 Participants Patients randomized to receive a single dose of 0.5 mg/kg Premarin® IV Premarin IV: One time dose of Premarin IV	Placebo n=26 Participants 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. Placebo: One time dose of Placebo
Acute Respiratory Distress Syndrome (ARDS) Free Survival	18.9 days Standard Deviation 13.2	24.1 days Standard Deviation 8.7

Adverse Events

Premarin IV

Serious events: 8 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 13 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Premarin IV n=22 participants at risk Patients randomized to receive a single dose of 0.5 mg/kg Premarin® IV Premarin IV: One time dose of Premarin IV	Placebo n=26 participants at risk Patients randomized to receive a single dose of placebo IV. Due to 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. Placebo: One time dose of Placebo
Infections and infestations Pneumonia	18.2% 4/22 • Number of events 4	34.6% 9/26 • Number of events 9
Infections and infestations Bloodstream infection	9.1% 2/22 • Number of events 2	11.5% 3/26 • Number of events 3
Infections and infestations Urinary tract infection	9.1% 2/22 • Number of events 2	19.2% 5/26 • Number of events 5
Infections and infestations Wound infection	9.1% 2/22 • Number of events 2	3.8% 1/26 • Number of events 1
Infections and infestations Pseudomembranous colitis	0.00% 0/22	3.8% 1/26 • Number of events 1
Infections and infestations Line infection	0.00% 0/22	3.8% 1/26 • Number of events 1
Vascular disorders Pulmonary embolus	4.5% 1/22 • Number of events 1	0.00% 0/26

Other adverse events

Adverse event data not reported

Additional Information

Scott Emerson, PhD

University of Washington

Phone: 206-616-6678

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place