Progesterone for the Treatment of Traumatic Brain Injury III
- Registration Number
- NCT00822900
- Lead Sponsor
- David Wright
- Brief Summary
The ProTECT study will determine if intravenous (IV) progesterone (started within 4 hours of injury and given for a total of 96 hours), is more effective than placebo for treating victims of moderate to severe acute traumatic brain injury.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 882
- Moderate to severe brain injury (GCS 12-4)
- Age 18 years or older
- Blunt, closed head injury
- Study drug initiated within 4 hours of injury
- Non-Survivable injury
- Bilateral dilated unresponsive pupils
- Severe intoxication (ETOH > 250 mg %)
- Spinal cord injury with neurological deficits
- Inability to perform activities of daily living prior to injury
- Cardiopulmonary arrest
- Status epilepticus on arrival
- Systolic blood pressure (SBP) < 90 on arrival or for at least 5 minutes prior to enrollment
- O2 Sat < 90 on arrival or for at least 5 minutes prior to enrollment
- Prisoner or ward of state
- Pregnant
- Active breast or reproductive organ cancers
- Known allergy to progesterone or intralipid components (egg yolk)
- Known history of clotting disorder
- Active thromboembolic event
- Concern for inability to follow up at 6 months
- Anyone listed in the Opt out registry
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo stock solution was the ethanol diluent required for dissolving progesterone. The volume of placebo to be mixed with intralipid was based on the same mg/kg/hr volume that would be required if PROG had been in the vial. Using an infusion pump through a dedicated IV line - a one hour "loading dose" of placebo plus intralipid was administered as a continuous intravenous infusion for 71 hours, then tapered over an additional 24 hours. To simplify the infusion protocol, a weight based dosing table was used by the on-sight pharmacy to mix the correct "dose" for a 10 cc/hour continuous infusion over the 72 hour steady state period followed by three additional 8-hour decrements (7.5 cc/hr-5.0 cc/hr-2.5 cc/hr) to zero, for a total treatment duration of 96 hour. The placebo will be combined with a 20% Intralipid mixture for infusion. Progesterone Progesterone Following a one hour loading dose of 0.714 mg/kg per infusion pump through a dedicated IV line, the study drug (progesterone) will be administered as a continuous intravenous infusion at 0.5 mg/kg/hr for 71 hours, then tapered over an additional 24 hours. To simplify the infusion protocol, a weight based dosing table will be used by the on-sight pharmacy to mix the correct dose for a 10 cc/hour continuous infusion over the 72 hour steady state period followed by three additional 8-hour decrements (7.5 cc/hr-5.0 cc/hr-2.5 cc/hr) to zero, for a total treatment duration of 96 hour. The progesterone will be combined with a 20% Intralipid mixture for infusion.
- Primary Outcome Measures
Name Time Method Favorable Outcome as Determined by the Glasgow Outcome Scale-Extended (GOSE) 6 months post randomization A measure of functional recovery: A GOS-E score of 1 indicates death, 2 indicates a vegetative state, 3 or 4 indicates severe disability, 5 or 6 indicates moderate disability, and 7 or 8 indicates good recovery. Favorable outcome was defined via stratified dichotomy based on the severity of the initial injury. For subjects with a severe injury, a GOS-E of 3 or higher were considered to be a favorable outcome; for subjects with moderate-to-severe injury, a GOS-E of 5 or higher was considered to be a favorable outcome; for subjects with a moderate injury, a GOS-E of 7 or higher was considered to be a favorable outcome.
- Secondary Outcome Measures
Name Time Method Disability Rating Scale 6 months A measure of functional impairment, with complete recovery scored a 0 and vegetative state scored a 29.
Potentially Associated Adverse Events: Sepsis within 6 months Sepsis - Events must have met Centers for Disease Control and Prevention (CDC) definition of sepsis. The definition includes that a patient ≤1 year of age has at least 1 of the following clinical signs or symptoms with no other recognized cause: fever (\>38°C rectal), hypothermia (\<37°C rectal), apnea, or bradycardia, and blood culture not done or no organisms detected in blood and no apparent infection at another site and physician institutes treatment for sepsis.
Mortality 6 months Potentially Associated Adverse Events: Phlebitis/Thrombophlebitis within 6 months Phlebitis/Thrombophlebitis (not due to infiltration or misplacement of the IV)
Potentially Associated Adverse Events: Pulmonary Embolism within 6 months Pulmonary embolism - Events were defined based on either positive chest computed tomography (CT) scanning or ventilation/perfusion lung scan (V/Q).
Potentially Associated Adverse Events: Acute Ischemic Stroke within 6 months Acute ischemic stroke - Events were defined based on either positive computed tomography (CT) scanning, magnetic resonance imaging (MRI), or neurologist diagnosis of cerebrovascular accident (CVA)
Potentially Associated Adverse Events: Pneumonia within 6 months Events must have met Centers for Disease Control and Prevention (CDC) definition of pneumonia. There are three specific types of pneumonia: clinically defined pneumonia, pneumonia with specific laboratory findings, and pneumonia in immunocompromised patients. There are specific algorithms to identify each pneumonia, which include x-ray findings, fever with no other cause, leukopenia or leukocytosis, altered mental status with no other cause (adults \>70 years old), new onset of purulent sputum, change in character of sputum, increase respiratory secretions, increase suctioning requirements, new onset or worsening cough, dyspnea, tachypnea, rales, bronchial breath sounds, or worsening gas exchange, increased oxygen requirements, or increased ventilator demand). Also, labs can identify pneumonia such as positive growth in blood culture, positive Gram stain, and histopathologic exam evidence.
Potentially Associated Adverse Events: Deep Venous Thrombosis (DVT) within 6 months DVT - Events were defined based on a positive Doppler ultrasound exam
Potentially Associated Adverse Events: Unexplained Increased Liver-enzyme Level within 6 months Unexplained increased liver enzymes (e.g. not due to liver injury ) - Events were defined based on aspartate transaminase (AST) and alanine transaminase (ALT) levels \> 500 U/L and/or total bilirubin levels \> 2.0 mg/dL.
Potentially Associated Adverse Events: Central Nervous System (CNS) Infection within 6 months CNS infection - Events must have met Centers for Disease Control and Prevention (CDC) definition of CNS infection. The definition includes intracranial infection, Meningitis, ventriculitis, and spinal abscess without meningitis.
Potentially Associated Adverse Events: Myocardial Infarction (MI) within 6 months Myocardial infarction - Events were defined based on serial cardiac enzyme elevation consistent with MI and/or new ST elevation on electrocardiogram (ECG) consistent with MI. Potentially associated adverse events (those events which are included as outcome measures) were specifically defined per the protocol, and the classification of an event as a PAAE was determined by the site. The reported name of the associated event, however, was subject to clinical judgement and case details; these were then further coded by the Principal Investigator. Since these data points do not share the same definition, there is no reason to expect perfect concordance. (For example, the potentially associated adverse event of myocardial infarction may include MedDRA codes other than myocardial infarction.)
Trial Locations
- Locations (36)
North Memorial Hospital
🇺🇸Robbinsdale, Minnesota, United States
Regional Medical Center-San Jose
🇺🇸San Jose, California, United States
Grady Memorial Hospital
🇺🇸Atlanta, Georgia, United States
University of Maryland Shock Trauma
🇺🇸Baltimore, Maryland, United States
Detroit Receiving Hospital
🇺🇸Detroit, Michigan, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Hurley Medical Center
🇺🇸Flint, Michigan, United States
Sinai Grace Hospital
🇺🇸Detroit, Michigan, United States
Hahnemann University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
University of Pennsylvania Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Thomas Jefferson UniversityHospital
🇺🇸Philadelphia, Pennsylvania, United States
Temple University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Maricopa Integrated Health System
🇺🇸Phoenix, Arizona, United States
Banner Good Samaritan
🇺🇸Phoenix, Arizona, United States
Scottsdale Healthcare
🇺🇸Scottsdale, Arizona, United States
University of Arizona Medical Center
🇺🇸Tuscon, Arizona, United States
Beaumont Royal Oak Hospital
🇺🇸Royal Oak, Michigan, United States
Oregon Health Sciences University
🇺🇸Portland, Oregon, United States
Regional Medical Center/Elvis Presley Memorial Trauma Center (The MED)
🇺🇸Memphis, Tennessee, United States
Froedtert East Hospital
🇺🇸Milwaukee, Wisconsin, United States
Stanford Medical Center
🇺🇸Palo Alto, California, United States
Columbia New York Presbyterian Hospital
🇺🇸New York, New York, United States
St. Johns Mercy Medical Center
🇺🇸St. Louis, Missouri, United States
San Francisco General Hospital
🇺🇸San Francisco, California, United States
University of Kentucky Medical Center
🇺🇸Lexington, Kentucky, United States
St. Luke's Hospital
🇺🇸Bethlehem, Pennsylvania, United States
University Hospital
🇺🇸Cincinnatti, Ohio, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
Penn State Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Memorial Hermann
🇺🇸Houston, Texas, United States
Brooke Army Medical Center
🇺🇸San Antonio, Texas, United States
Austin/Brackenridge
🇺🇸Austin, Texas, United States
Virginia Commonwealth
🇺🇸Richmond, Virginia, United States
Regions Hospital
🇺🇸St. Paul, Minnesota, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
Santa Clara Valley Hospital
🇺🇸Palo Alto, California, United States