Progesterone for the Treatment of Traumatic Brain Injury III

Browse trials for

• Brain Injuries 2,113
• Brain Injuries, Traumatic 1,775
• Wounds and Injuries 5,056

Keywords

• Trauma
• Brain Injury

Brain Injuries

2,113 studies on the registry are indexed under Brain Injuries; 385 are open to participants now.

This study's enrollment of 882 is above the median of 48 across 1,331 interventional studies indexed under Brain Injuries.

Lead sponsor

David Wright is the lead sponsor of 2 studies on the registry; none are open to participants now.

Study arms

• 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.

  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.

  Drug: Placebo

Interventions

• DrugProgesterone

  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.

• DrugPlacebo

  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.

Primary outcomes

1. 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.

   Time frame: 6 months post randomization

Secondary outcomes

1. Mortality

   Time frame: 6 months

2. Disability Rating Scale

   A measure of functional impairment, with complete recovery scored a 0 and vegetative state scored a 29.

   Time frame: 6 months

3. Potentially Associated Adverse Events: Phlebitis/Thrombophlebitis

   Phlebitis/Thrombophlebitis (not due to infiltration or misplacement of the IV)

   Time frame: within 6 months

4. 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).

   Time frame: within 6 months

5. 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)

   Time frame: within 6 months

6. Potentially Associated Adverse Events: Deep Venous Thrombosis (DVT)

   DVT - Events were defined based on a positive Doppler ultrasound exam

   Time frame: within 6 months

7. 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.

   Time frame: within 6 months

8. 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.

   Time frame: within 6 months

9. 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.

   Time frame: within 6 months

10. 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.

    Time frame: within 6 months

11. 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.)

    Time frame: within 6 months

Baseline characteristics

Publications

• Zhao W, Pauls K. Architecture design of a generic centralized adjudication module integrated in a web-based clinical trial management system. Clin Trials. 2016 Apr;13(2):223-33. doi: 10.1177/1740774515611889. Epub 2015 Oct 13. PubMed 26464429 ↗
• 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. PubMed 25493974 ↗