Efficacy and Safety Study of Intravenous Progesterone in Patients With Severe Traumatic Brain Injury

Study Overview
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Brief Summary
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The SyNAPSe trial will study if giving intravenous (i.v.) progesterone within 8 hours of the injury for a total of 120 hours to severe traumatic brain injury patients improves their recovery.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study to Investigate the Efficacy and Safety of Progesterone in Patients With Severe Traumatic Brain Injury

Conditions
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Brain Injuries

Intervention / Treatment
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* Drug: Progesterone
* Drug: Lipid emulsion without progesterone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients between the age of 16 and 70 years, inclusive Weight from 45 to 135 kg, inclusive Sustained a closed head trauma no more than 8 hours before start of study drug infusion TBI diagnosed by history and clinical examination Post-resuscitation Glasgow Coma Scale (GCS) score between 3 to 8, inclusive At least one reactive pupil (pinpoint pupils due to opioid pain treatment are considered reactive) Evidence of TBI confirmed by abnormalities consistent with trauma on CT scan upon admission (diffuse injury II-IV, evacuated and non-evacuated mass lesion, Marshall's CT Classification) Indication for ICP monitoring Exclusion Criteria: Life expectancy of less than 24 hours as determined by the Investigator Prolonged and/or uncorrectable hypoxia (Pa02< 60 mmHg) or hypotension (systolic blood pressure < 90 mmHg) at the time of randomization Any spinal cord injury Pregnancy Penetrating head injury Bilaterally fixed dilated pupils at the time of randomization Coma suspected to be primarily due to other causes (e.g. alcohol) Pure epidural hematoma Preexisting clinically significant disease or chronic condition that can be ascertained at the time of admission and could affect functional outcome Severe cardiac or hemodynamic instability prior to randomization Known treatment with another investigational drug therapy or procedure within 30 days of injury A history of allergic reaction to progesterone and related drugs or any of the components of the infusion Any disease, in the opinion of the Investigator, that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study. Patients who, in the opinion of the Investigator, would not be able or willing to comply with the protocol through the final visit (6 months post-injury)

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Progesterone<br> | Drug: Progesterone<br>* Intravenous administration of 0.71mg/kg/hr for 1hr followed by 0.5mg/kg/hr administered intravenously for an additional 119 hrs.<br>* Other names: BHR-100;|
| Placebo Comparator: Lipid emulsion without progestrone<br> | Drug: Lipid emulsion without progesterone<br>* Intravenous administration equal to 0.71mg/kg/hr for 1hr followed by 0.5mg/kg/hr administered intravenously for an additional 119 hrs.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glasgow Outcome Scale (GOS) | The GOS (Jennett and Bond, 1975) assesses mortality and disability in traumatic brain injury (TBI) patients according to the designation: Good Recovery, Moderate Disability, Severe Disability, Vegetative State or Dead. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | The mortality rate at one and six months will be compared between the two treatment groups. | 1 month and 6 months post injury | 
| Glasgow Outcome Scale |  | Month 3 | 
| Glasgow Outcome Scale - Extended (GOS-E) | The GOS-E assessment of mortality and disability in TBI patients extends the original five GOS categories of functional outcome to eight categories: Dead Vegetative State Lower Severe Disability Upper Severe Disability Lower Moderate Disability Upper Moderate Disability Lower Good Recovery Upper Good Recovery | 3 months and 6 months post injury | 
| Short Form (36) Health Survey (SF-36) | The SF-36 is a validated survey of patient health consisting of eight scaled scores. The eight sections are: vitality physical functioning bodily pain general health perceptions role physical role emotional role mental mental health The 8 scales can also be further summarized to provide a summary score for physical health and a summary score for mental health. | 3 months and 6 months post injury | 
| Effect of progesterone on Intracranial Pressure (ICP), Cerebral Perfusion Pressure (CPP), and Therapeutic Intensity Level (TIL) |  | Admission through post-infusion Day 6 | 
| Effect of progesterone on the progression of intracranial pathology |  | Admission and Day 6 computed tomography (CT) scans | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brain Injury, Trauma