Progesterone for the Treatment of Traumatic Brain Injury III (ProTECT)

This study has been terminated.
(futility: low conditional power to demonstrate benefit of progesterone)
Sponsor:
Collaborators:
Medical University of South Carolina
Neurological Emergencies Treatment Trials Network (NETT)
Information provided by (Responsible Party):
David Wright, Emory University
ClinicalTrials.gov Identifier:
NCT00822900
First received: January 14, 2009
Last updated: June 24, 2015
Last verified: June 2015

January 14, 2009
June 24, 2015
March 2010
May 2014   (final data collection date for primary outcome measure)
Favorable Outcome as Determined by the Glasgow Outcome Scale-Extended (GOSE) [ Time Frame: 6 months post randomization ] [ Designated as safety issue: No ]
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.
Progesterone will significantly increase the proportion of patients with a favorable outcome as determined by the Glasgow Outcome Scale-Extended (GOSE) score at 6 months post injury when compared to placebo. [ Time Frame: unknown ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00822900 on ClinicalTrials.gov Archive Site
  • Mortality [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Disability Rating Scale [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    A measure of functional impairment, with complete recovery scored a 0 and vegetative state scored a 29.
  • Potentially Associated Adverse Events: Phlebitis/Thrombophlebitis [ Time Frame: within 6 months ] [ Designated as safety issue: Yes ]
    Phlebitis/Thrombophlebitis (not due to infiltration or misplacement of the IV)
  • Potentially Associated Adverse Events: Pulmonary Embolism [ Time Frame: within 6 months ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: within 6 months ] [ Designated as safety issue: Yes ]
    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: Deep Venous Thrombosis (DVT) [ Time Frame: within 6 months ] [ Designated as safety issue: Yes ]
    DVT - Events were defined based on a positive Doppler ultrasound exam
  • Potentially Associated Adverse Events: Unexplained Increased Liver-enzyme Level [ Time Frame: within 6 months ] [ Designated as safety issue: Yes ]
    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: Sepsis [ Time Frame: within 6 months ] [ Designated as safety issue: Yes ]
    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.
  • Potentially Associated Adverse Events: Pneumonia [ Time Frame: within 6 months ] [ Designated as safety issue: Yes ]
    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: Central Nervous System (CNS) Infection [ Time Frame: within 6 months ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: within 6 months ] [ Designated as safety issue: Yes ]
    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.)
Examine the efficacy of IV progesterone vs. placebo for treating patients with moderate to severe TBI on additional 6 month outcomes: Mortality, DRS, cognitive, neurological and functional outcomes, and rates of AE's and SAE's. [ Time Frame: unknown ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Progesterone for the Treatment of Traumatic Brain Injury III
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.

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Traumatic Brain Injury
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.
  • Experimental: 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.
    Intervention: Drug: Progesterone
  • Placebo Comparator: 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.
Wright DW, Yeatts SD, Silbergleit R, Palesch YY, Hertzberg VS, Frankel M, Goldstein FC, Caveney AF, Howlett-Smith H, Bengelink EM, Manley GT, Merck LH, Janis LS, Barsan WG; NETT Investigators. Very early administration of progesterone for acute traumatic brain injury. N Engl J Med. 2014 Dec 25;371(26):2457-66. doi: 10.1056/NEJMoa1404304. Epub 2014 Dec 10.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
882
July 2014
May 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00822900
IRB00014409, 1RO1 NS062778-01
Yes
David Wright, Emory University
David Wright
  • Medical University of South Carolina
  • Neurological Emergencies Treatment Trials Network (NETT)
Principal Investigator: David W Wright, MD Emory University
Emory University
June 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP