Progesterone for the Treatment of Traumatic Brain Injury III

Traumatic Brain Injury Clinical Trial

— ProTECT  

Official title:

Phase 3 Clinical Trial to Determine if Progesterone Along With Standard Medical Care for Brain Injury is More Effective at Limiting the Amount of Damage Cause by a Traumatic Brain Injury Than Standard Medical Care Alone.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00822900
• Other study ID #: IRB00014409
• Secondary ID: 1RO1 NS062778-01
• Status: Terminated
• Phase: Phase 3
• First received: January 14, 2009
• Last updated: December 16, 2015
• Start date: March 2010
• Est. completion date: July 2014

Study information

• Verified date: December 2015
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 882
• Est. completion date: July 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Injuries
• Traumatic Brain Injury

Intervention

Drug:
• Progesterone
Following a one hour loading dose of 0.714 mg/kg per infusion pump through a dedicated IV line, the study drug (progesterone or placebo) 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 71 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/placebo will be combined with a 20% Intralipid mixture for infusion.
• Placebo
Placebo stock solution is the ethanol diluent required for dissolving progesterone. The volume of placebo to be mixed with intralipid is based on the mg/kg/hr volume. Using an infusion pump through a dedicated IV line - a one hour "loading dose" of placebo plus intralipid is administered as a continuous intravenous infusion for 71 hours, then tapered over an additional 24 hours.

Locations

Country	Name	City	State
United States	Grady Memorial Hospital	Atlanta	Georgia
United States	Austin/Brackenridge	Austin	Texas
United States	University of Maryland Shock Trauma	Baltimore	Maryland
United States	St. Luke's Hospital	Bethlehem	Pennsylvania
United States	University Hospital	Cincinnatti	Ohio
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Detroit Receiving Hospital	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Sinai Grace Hospital	Detroit	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Memorial Hermann	Houston	Texas
United States	University of Kentucky Medical Center	Lexington	Kentucky
United States	Regional Medical Center/Elvis Presley Memorial Trauma Center (The MED)	Memphis	Tennessee
United States	Froedtert East Hospital	Milwaukee	Wisconsin
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Columbia New York Presbyterian Hospital	New York	New York
United States	Santa Clara Valley Hospital	Palo Alto	California
United States	Stanford Medical Center	Palo Alto	California
United States	Hahnemann University Hospital	Philadelphia	Pennsylvania
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Thomas Jefferson UniversityHospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	Banner Good Samaritan	Phoenix	Arizona
United States	Maricopa Integrated Health System	Phoenix	Arizona
United States	Oregon Health Sciences University	Portland	Oregon
United States	Virginia Commonwealth	Richmond	Virginia
United States	North Memorial Hospital	Robbinsdale	Minnesota
United States	Beaumont Royal Oak Hospital	Royal Oak	Michigan
United States	Brooke Army Medical Center	San Antonio	Texas
United States	San Francisco General Hospital	San Francisco	California
United States	Regional Medical Center-San Jose	San Jose	California
United States	Scottsdale Healthcare	Scottsdale	Arizona
United States	St. Johns Mercy Medical Center	St. Louis	Missouri
United States	Regions Hospital	St. Paul	Minnesota
United States	University of Arizona Medical Center	Tuscon	Arizona

Sponsors (3)

Lead Sponsor	Collaborator
David Wright	Medical University of South Carolina, Neurological Emergencies Treatment Trials Network (NETT)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Favorable Outcome as Determined by the Glasgow Outcome Scale-Extended (GOSE)	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.	6 months post randomization	No
Secondary	Mortality		6 months	Yes
Secondary	Disability Rating Scale	A measure of functional impairment, with complete recovery scored a 0 and vegetative state scored a 29.	6 months	No
Secondary	Potentially Associated Adverse Events: Phlebitis/Thrombophlebitis	Phlebitis/Thrombophlebitis (not due to infiltration or misplacement of the IV)	within 6 months	Yes
Secondary	Potentially Associated Adverse Events: Pulmonary Embolism	Pulmonary embolism - Events were defined based on either positive chest computed tomography (CT) scanning or ventilation/perfusion lung scan (V/Q).	within 6 months	Yes
Secondary	Potentially Associated Adverse Events: Acute Ischemic Stroke	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)	within 6 months	Yes
Secondary	Potentially Associated Adverse Events: Deep Venous Thrombosis (DVT)	DVT - Events were defined based on a positive Doppler ultrasound exam	within 6 months	Yes
Secondary	Potentially Associated Adverse Events: Unexplained Increased Liver-enzyme Level	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.	within 6 months	Yes
Secondary	Potentially Associated Adverse Events: Sepsis	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.	within 6 months	Yes
Secondary	Potentially Associated Adverse Events: Pneumonia	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.	within 6 months	Yes
Secondary	Potentially Associated Adverse Events: Central Nervous System (CNS) Infection	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.	within 6 months	Yes
Secondary	Potentially Associated Adverse Events: Myocardial Infarction (MI)	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.)	within 6 months	Yes

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