Brain Injuries
Conditions
Keywords
Brain Injury, Trauma
Brief summary
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.
Interventions
DRUGProgesterone
Intravenous administration of 0.71mg/kg/hr for 1hr followed by 0.5mg/kg/hr administered intravenously for an additional 119 hrs.
DRUGLipid emulsion without progesterone
Intravenous administration equal to 0.71mg/kg/hr for 1hr followed by 0.5mg/kg/hr administered intravenously for an additional 119 hrs.
Sponsors
PRA Health Sciences
Syneos Health
BHR Pharma, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female patients between the age of 16 and 70 years, inclusive 2. Weight from 45 to 135 kg, inclusive 3. Sustained a closed head trauma no more than 8 hours before start of study drug infusion 4. TBI diagnosed by history and clinical examination 5. Post-resuscitation Glasgow Coma Scale (GCS) score between 3 to 8, inclusive 6. At least one reactive pupil (pinpoint pupils due to opioid pain treatment are considered reactive) 7. 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) 8. Indication for ICP monitoring
Exclusion criteria
1. Life expectancy of less than 24 hours as determined by the Investigator 2. Prolonged and/or uncorrectable hypoxia (Pa02\< 60 mmHg) or hypotension (systolic blood pressure \< 90 mmHg) at the time of randomization 3. Any spinal cord injury 4. Pregnancy 5. Penetrating head injury 6. Bilaterally fixed dilated pupils at the time of randomization 7. Coma suspected to be primarily due to other causes (e.g. alcohol) 8. Pure epidural hematoma 9. Preexisting clinically significant disease or chronic condition that can be ascertained at the time of admission and could affect functional outcome 10. Severe cardiac or hemodynamic instability prior to randomization 11. Known treatment with another investigational drug therapy or procedure within 30 days of injury 12. A history of allergic reaction to progesterone and related drugs or any of the components of the infusion 13. 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. 14. 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glasgow Outcome Scale (GOS) | 6 months | The GOS assesses mortality and disability in traumatic brain injury (TBI) patients according to the designation: Good Recovery, Moderate Disability, Severe Disability, Vegetative State or Dead. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mortality at Month 6 | 6 months post injury | The mortality rate at six months will be compared between the two treatment groups. |
| Glasgow Outcome Scale at 3 Months | Month 3 | The GOS assesses the mortality and disability in traumatic brain injury patients according to the designation: Good Recovery, Moderate Disability, Severe Disability, Vegetative State, or Dead. |
| Mortality at Month 1 | 1 month post injury | The mortality rate at one month will be compared between the two treatment groups. |
| Short Form (36) Health Survey (SF-36) | 3 months and 6 months post injury | The Short Form (36) Health Survey (SF-36) is a validated survey of patient health consisting of eight scaled scores which are the weighted sums of the questions in their section. The eight sections are: vitality, physical functioning, bodily pain, general health perceptions, role physical, role emotional, role mental and mental health. The maximum score is 30. A score of 23 or lower is indicative of cognitive impairment. The 8 scales can also be further summarized to provide a summary score for physical health and a summary score for mental health. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. |
| Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL) | Admission through post-infusion Day 6 | Cerebral Perfusion Pressure (CPP) levels are presented according to clinically significant cut-off values. CPP was calculated from intracranial pressures and mean arterial pressures measured from Day through Day 6 after initiation of study medication, if an ICP monitor was in place. Specific therapies received during Days 1-6 are summarized according to the Therapeutic Intensity Level (TIL) by treatment group, as maximum level of therapy administered to the subject. |
| Glasgow Outcome Scale - Extended (GOS-E) | 3 months and 6 months post injury | 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 |
Countries
Argentina, Austria, Belgium, China, Czechia, Finland, France, Germany, Hungary, Israel, Italy, Malaysia, Netherlands, Romania, Russia, Singapore, Spain, Taiwan, Thailand, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BHR-100 Progesterone: Intravenous administration of 0.71mg/kg/hr for 1hr followed by 0.5mg/kg/hr administered intravenously for an additional 119 hrs. | 591 |
| Placebo Lipid emulsion without progesterone: Intravenous administration equal to 0.71mg/kg/hr for 1hr followed by 0.5mg/kg/hr administered intravenously for an additional 119 hrs. | 588 |
| Total | 1,179 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Death | 109 | 91 |
| Overall Study | Lost to Follow-up | 17 | 14 |
| Overall Study | Physician Decision | 0 | 4 |
| Overall Study | Withdrawal by Subject | 7 | 5 |
Baseline characteristics
| Characteristic | Total | BHR-100 | Placebo |
|---|---|---|---|
| Age, Continuous | 37.4 years STANDARD_DEVIATION 15.47 | 37.3 years STANDARD_DEVIATION 15.6 | 37.6 years STANDARD_DEVIATION 15.36 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 121 Participants | 61 Participants | 60 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 966 Participants | 479 Participants | 487 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 92 Participants | 51 Participants | 41 Participants |
| Glasgow Coma Score Motor Score 1-2 | 296 Participants | 129 Participants | 167 Participants |
| Glasgow Coma Score Motor Score 3 | 158 Participants | 84 Participants | 74 Participants |
| Glasgow Coma Score Motor Score 4 | 327 Participants | 167 Participants | 160 Participants |
| Glasgow Coma Score Motor Score 5-6 | 394 Participants | 209 Participants | 185 Participants |
| Glasgow Coma Score Motor Score Missing | 4 Participants | 2 Participants | 2 Participants |
| Hypotension No | 982 Participants | 484 Participants | 498 Participants |
| Hypotension Suspected | 20 Participants | 8 Participants | 12 Participants |
| Hypotension Unknown | 26 Participants | 14 Participants | 12 Participants |
| Hypotension Yes | 151 Participants | 85 Participants | 66 Participants |
| Hypoxia No | 1044 Participants | 523 Participants | 521 Participants |
| Hypoxia Suspected | 69 Participants | 37 Participants | 32 Participants |
| Hypoxia Unknown | 38 Participants | 16 Participants | 22 Participants |
| Hypoxia Yes | 28 Participants | 15 Participants | 13 Participants |
| Marshall CT Classification Evacuated/Non-Evacuated Mass Lesion | 285 Participants | 134 Participants | 151 Participants |
| Marshall CT Classification I | 10 Participants | 6 Participants | 4 Participants |
| Marshall CT Classification II | 468 Participants | 235 Participants | 233 Participants |
| Marshall CT Classification III | 342 Participants | 178 Participants | 164 Participants |
| Marshall CT Classification IV | 70 Participants | 35 Participants | 35 Participants |
| Marshall CT Classification Missing | 4 Participants | 3 Participants | 1 Participants |
| Pupillary Response Bilateral | 955 Participants | 480 Participants | 475 Participants |
| Pupillary Response Missing | 1 Participants | 0 Participants | 1 Participants |
| Pupillary Response No Reactive Pupils | 1 Participants | 0 Participants | 1 Participants |
| Pupillary Response Not Testable | 6 Participants | 2 Participants | 4 Participants |
| Pupillary Response Unilateral | 216 Participants | 109 Participants | 107 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 126 Participants | 63 Participants | 63 Participants |
| Race/Ethnicity, Customized Black/African American/African Heritage | 39 Participants | 23 Participants | 16 Participants |
| Race/Ethnicity, Customized Native Hawaiian/other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Allowed to Obtain | 92 Participants | 51 Participants | 41 Participants |
| Race/Ethnicity, Customized Other | 21 Participants | 11 Participants | 10 Participants |
| Race/Ethnicity, Customized White | 899 Participants | 441 Participants | 458 Participants |
| Region of Enrollment Argentina | 64 participants | 31 participants | 33 participants |
| Region of Enrollment Austria | 32 participants | 18 participants | 14 participants |
| Region of Enrollment Belgium | 29 participants | 16 participants | 13 participants |
| Region of Enrollment China | 35 participants | 20 participants | 15 participants |
| Region of Enrollment Czechia | 58 participants | 24 participants | 34 participants |
| Region of Enrollment Finland | 6 participants | 5 participants | 1 participants |
| Region of Enrollment France | 92 participants | 51 participants | 41 participants |
| Region of Enrollment Germany | 50 participants | 24 participants | 26 participants |
| Region of Enrollment Hungary | 8 participants | 3 participants | 5 participants |
| Region of Enrollment Israel | 62 participants | 37 participants | 25 participants |
| Region of Enrollment Italy | 46 participants | 22 participants | 24 participants |
| Region of Enrollment Malaysia | 19 participants | 11 participants | 8 participants |
| Region of Enrollment Netherlands | 7 participants | 2 participants | 5 participants |
| Region of Enrollment Romania | 6 participants | 5 participants | 1 participants |
| Region of Enrollment Russia | 13 participants | 6 participants | 7 participants |
| Region of Enrollment Singapore | 15 participants | 6 participants | 9 participants |
| Region of Enrollment Spain | 93 participants | 42 participants | 51 participants |
| Region of Enrollment Taiwan | 5 participants | 3 participants | 2 participants |
| Region of Enrollment Thailand | 46 participants | 22 participants | 24 participants |
| Region of Enrollment United Kingdom | 54 participants | 24 participants | 30 participants |
| Region of Enrollment United States | 439 participants | 219 participants | 220 participants |
| Sex: Female, Male Female | 252 Participants | 127 Participants | 125 Participants |
| Sex: Female, Male Male | 927 Participants | 464 Participants | 463 Participants |
| Traumatic Subarachnoid Hemorrhage Missing | 5 Participants | 4 Participants | 1 Participants |
| Traumatic Subarachnoid Hemorrhage No | 269 Participants | 138 Participants | 131 Participants |
| Traumatic Subarachnoid Hemorrhage Yes | 905 Participants | 449 Participants | 456 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 109 / 596 | 95 / 583 |
| other Total, other adverse events | 265 / 596 | 286 / 583 |
| serious Total, serious adverse events | 224 / 596 | 214 / 583 |
Outcome results
Primary
Glasgow Outcome Scale (GOS)
The GOS assesses mortality and disability in traumatic brain injury (TBI) patients according to the designation: Good Recovery, Moderate Disability, Severe Disability, Vegetative State or Dead.
Time frame: 6 months
Population: Only participants with data for this outcome are included. Missing values are first imputed by carrying forward the Month 3 GOS assessment. If a subject has neither the 3 nor the 6 month GOS, the missing value is imputed using the proportional odds model.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BHR-100 | Glasgow Outcome Scale (GOS) | Good Recovery | 189 Participants |
| BHR-100 | Glasgow Outcome Scale (GOS) | Moderate Disability | 109 Participants |
| BHR-100 | Glasgow Outcome Scale (GOS) | Severe Disability | 162 Participants |
| BHR-100 | Glasgow Outcome Scale (GOS) | Vegetative State/Dead | 131 Participants |
| Placebo | Glasgow Outcome Scale (GOS) | Vegetative State/Dead | 131 Participants |
| Placebo | Glasgow Outcome Scale (GOS) | Good Recovery | 183 Participants |
| Placebo | Glasgow Outcome Scale (GOS) | Severe Disability | 160 Participants |
| Placebo | Glasgow Outcome Scale (GOS) | Moderate Disability | 114 Participants |
Secondary
Glasgow Outcome Scale at 3 Months
The GOS assesses the mortality and disability in traumatic brain injury patients according to the designation: Good Recovery, Moderate Disability, Severe Disability, Vegetative State, or Dead.
Time frame: Month 3
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BHR-100 | Glasgow Outcome Scale at 3 Months | Good Recovery | 103 Participants |
| BHR-100 | Glasgow Outcome Scale at 3 Months | Moderate Disability | 103 Participants |
| BHR-100 | Glasgow Outcome Scale at 3 Months | Severe Disability | 224 Participants |
| BHR-100 | Glasgow Outcome Scale at 3 Months | Vegetative State | 33 Participants |
| BHR-100 | Glasgow Outcome Scale at 3 Months | Dead | 102 Participants |
| BHR-100 | Glasgow Outcome Scale at 3 Months | Missing | 26 Participants |
| Placebo | Glasgow Outcome Scale at 3 Months | Dead | 88 Participants |
| Placebo | Glasgow Outcome Scale at 3 Months | Good Recovery | 101 Participants |
| Placebo | Glasgow Outcome Scale at 3 Months | Vegetative State | 49 Participants |
| Placebo | Glasgow Outcome Scale at 3 Months | Moderate Disability | 114 Participants |
| Placebo | Glasgow Outcome Scale at 3 Months | Missing | 20 Participants |
| Placebo | Glasgow Outcome Scale at 3 Months | Severe Disability | 216 Participants |
Secondary
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
Time frame: 3 months and 6 months post injury
Population: Number analyzed (591 for BHR-100 and 588 for placebo) is as listed in the clinical study report. The number analyzed was not modified per time frame and outcome, rather 591 and 588 are included.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BHR-100 | Glasgow Outcome Scale - Extended (GOS-E) | Dead - 3 months | 102 Participants |
| BHR-100 | Glasgow Outcome Scale - Extended (GOS-E) | Vegetative State - 3 months | 33 Participants |
| BHR-100 | Glasgow Outcome Scale - Extended (GOS-E) | Lower Severe Disability - 3 months | 173 Participants |
| BHR-100 | Glasgow Outcome Scale - Extended (GOS-E) | Upper Severe Disability - 3 months | 51 Participants |
| BHR-100 | Glasgow Outcome Scale - Extended (GOS-E) | Lower Moderate Disability - 3 months | 35 Participants |
| BHR-100 | Glasgow Outcome Scale - Extended (GOS-E) | Upper Moderate Disability - 3 months | 68 Participants |
| BHR-100 | Glasgow Outcome Scale - Extended (GOS-E) | Lower Good Recovery - 3 months | 53 Participants |
| BHR-100 | Glasgow Outcome Scale - Extended (GOS-E) | Upper Good Recovery - 3 months | 50 Participants |
| BHR-100 | Glasgow Outcome Scale - Extended (GOS-E) | Dead - 6 months | 109 Participants |
| BHR-100 | Glasgow Outcome Scale - Extended (GOS-E) | Vegetative State - 6 months | 20 Participants |
| BHR-100 | Glasgow Outcome Scale - Extended (GOS-E) | Lower Severe Disability - 6 months | 115 Participants |
| BHR-100 | Glasgow Outcome Scale - Extended (GOS-E) | Upper Severe Disability - 6 months | 37 Participants |
| BHR-100 | Glasgow Outcome Scale - Extended (GOS-E) | Lower Moderate Disability - 6 months | 36 Participants |
| BHR-100 | Glasgow Outcome Scale - Extended (GOS-E) | Upper Moderate Disability - 6 months | 70 Participants |
| BHR-100 | Glasgow Outcome Scale - Extended (GOS-E) | Lower Good Recovery - 6 months | 71 Participants |
| BHR-100 | Glasgow Outcome Scale - Extended (GOS-E) | Upper Good Recovery - 6 months | 108 Participants |
| Placebo | Glasgow Outcome Scale - Extended (GOS-E) | Upper Good Recovery - 6 months | 109 Participants |
| Placebo | Glasgow Outcome Scale - Extended (GOS-E) | Dead - 3 months | 88 Participants |
| Placebo | Glasgow Outcome Scale - Extended (GOS-E) | Dead - 6 months | 95 Participants |
| Placebo | Glasgow Outcome Scale - Extended (GOS-E) | Vegetative State - 3 months | 49 Participants |
| Placebo | Glasgow Outcome Scale - Extended (GOS-E) | Lower Moderate Disability - 6 months | 38 Participants |
| Placebo | Glasgow Outcome Scale - Extended (GOS-E) | Lower Severe Disability - 3 months | 165 Participants |
| Placebo | Glasgow Outcome Scale - Extended (GOS-E) | Vegetative State - 6 months | 33 Participants |
| Placebo | Glasgow Outcome Scale - Extended (GOS-E) | Upper Severe Disability - 3 months | 51 Participants |
| Placebo | Glasgow Outcome Scale - Extended (GOS-E) | Lower Good Recovery - 6 months | 64 Participants |
| Placebo | Glasgow Outcome Scale - Extended (GOS-E) | Lower Moderate Disability - 3 months | 34 Participants |
| Placebo | Glasgow Outcome Scale - Extended (GOS-E) | Lower Severe Disability - 6 months | 109 Participants |
| Placebo | Glasgow Outcome Scale - Extended (GOS-E) | Upper Moderate Disability - 3 months | 80 Participants |
| Placebo | Glasgow Outcome Scale - Extended (GOS-E) | Upper Moderate Disability - 6 months | 72 Participants |
| Placebo | Glasgow Outcome Scale - Extended (GOS-E) | Lower Good Recovery - 3 months | 46 Participants |
| Placebo | Glasgow Outcome Scale - Extended (GOS-E) | Upper Severe Disability - 6 months | 44 Participants |
| Placebo | Glasgow Outcome Scale - Extended (GOS-E) | Upper Good Recovery - 3 months | 55 Participants |
Secondary
Mortality at Month 1
The mortality rate at one month will be compared between the two treatment groups.
Time frame: 1 month post injury
Population: P-value population size is based on the number of subjects with status = alive or dead, month 6 within the mITT population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BHR-100 | Mortality at Month 1 | Lost to Follow-up | 0 Participants |
| BHR-100 | Mortality at Month 1 | Consent Withdrawn | 0 Participants |
| BHR-100 | Mortality at Month 1 | Alive | 500 Participants |
| BHR-100 | Mortality at Month 1 | Dead | 87 Participants |
| BHR-100 | Mortality at Month 1 | Other | 1 Participants |
| BHR-100 | Mortality at Month 1 | Missing | 3 Participants |
| Placebo | Mortality at Month 1 | Other | 0 Participants |
| Placebo | Mortality at Month 1 | Lost to Follow-up | 0 Participants |
| Placebo | Mortality at Month 1 | Dead | 74 Participants |
| Placebo | Mortality at Month 1 | Consent Withdrawn | 0 Participants |
| Placebo | Mortality at Month 1 | Missing | 7 Participants |
| Placebo | Mortality at Month 1 | Alive | 507 Participants |
Secondary
Mortality at Month 6
The mortality rate at six months will be compared between the two treatment groups.
Time frame: 6 months post injury
Population: P-value population size is based on the number of subjects with status = alive or dead, month 6 within the mITT population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BHR-100 | Mortality at Month 6 | Consent Withdrawn | 0 Participants |
| BHR-100 | Mortality at Month 6 | Lost to Follow-up | 0 Participants |
| BHR-100 | Mortality at Month 6 | Alive | 463 Participants |
| BHR-100 | Mortality at Month 6 | Dead | 109 Participants |
| BHR-100 | Mortality at Month 6 | Other | 0 Participants |
| BHR-100 | Mortality at Month 6 | Missing | 19 Participants |
| Placebo | Mortality at Month 6 | Other | 0 Participants |
| Placebo | Mortality at Month 6 | Consent Withdrawn | 0 Participants |
| Placebo | Mortality at Month 6 | Dead | 95 Participants |
| Placebo | Mortality at Month 6 | Lost to Follow-up | 2 Participants |
| Placebo | Mortality at Month 6 | Missing | 19 Participants |
| Placebo | Mortality at Month 6 | Alive | 472 Participants |
Secondary
Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL)
Cerebral Perfusion Pressure (CPP) levels are presented according to clinically significant cut-off values. CPP was calculated from intracranial pressures and mean arterial pressures measured from Day through Day 6 after initiation of study medication, if an ICP monitor was in place. Specific therapies received during Days 1-6 are summarized according to the Therapeutic Intensity Level (TIL) by treatment group, as maximum level of therapy administered to the subject.
Time frame: Admission through post-infusion Day 6
Population: Only participants with data for these parameters have been included.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BHR-100 | Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL) | Any CPP value < 50 mmHg | 130 Participants |
| BHR-100 | Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL) | Any CPP value >=50-<60 mmHg | 297 Participants |
| BHR-100 | Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL) | Any CPP value >=60-<70 mmHg | 448 Participants |
| BHR-100 | Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL) | Any CPP value >=70 mmHg | 518 Participants |
| BHR-100 | Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL) | Surgical Decompression (TIL) | 192 Participants |
| BHR-100 | Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL) | Barbiturate Induced Coma (TIL) | 82 Participants |
| BHR-100 | Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL) | Hypothermia (TIL) | 61 Participants |
| BHR-100 | Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL) | Hyperventilation (TIL) | 78 Participants |
| BHR-100 | Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL) | Pressor Administered (TIL) | 315 Participants |
| BHR-100 | Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL) | Hypertonic Saline (TIL) | 225 Participants |
| BHR-100 | Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL) | Mannitol (TIL) | 288 Participants |
| BHR-100 | Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL) | Ventricular Drainage (TIL) | 198 Participants |
| BHR-100 | Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL) | Paralysis Induction (TIL) | 220 Participants |
| BHR-100 | Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL) | Sedation (TIL) | 565 Participants |
| Placebo | Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL) | Mannitol (TIL) | 285 Participants |
| Placebo | Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL) | Any CPP value < 50 mmHg | 155 Participants |
| Placebo | Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL) | Hyperventilation (TIL) | 68 Participants |
| Placebo | Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL) | Any CPP value >=50-<60 mmHg | 299 Participants |
| Placebo | Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL) | Paralysis Induction (TIL) | 231 Participants |
| Placebo | Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL) | Any CPP value >=60-<70 mmHg | 460 Participants |
| Placebo | Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL) | Pressor Administered (TIL) | 343 Participants |
| Placebo | Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL) | Any CPP value >=70 mmHg | 523 Participants |
| Placebo | Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL) | Ventricular Drainage (TIL) | 208 Participants |
| Placebo | Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL) | Surgical Decompression (TIL) | 174 Participants |
| Placebo | Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL) | Hypertonic Saline (TIL) | 233 Participants |
| Placebo | Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL) | Barbiturate Induced Coma (TIL) | 73 Participants |
| Placebo | Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL) | Sedation (TIL) | 565 Participants |
| Placebo | Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL) | Hypothermia (TIL) | 69 Participants |
Secondary
Short Form (36) Health Survey (SF-36)
The Short Form (36) Health Survey (SF-36) is a validated survey of patient health consisting of eight scaled scores which are the weighted sums of the questions in their section. The eight sections are: vitality, physical functioning, bodily pain, general health perceptions, role physical, role emotional, role mental and mental health. The maximum score is 30. A score of 23 or lower is indicative of cognitive impairment. The 8 scales can also be further summarized to provide a summary score for physical health and a summary score for mental health. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Time frame: 3 months and 6 months post injury
Population: Only participants with data for these parameters have been included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BHR-100 | Short Form (36) Health Survey (SF-36) | Mental Composite Summary - Month 3 | 48.7 score on a scale | Standard Deviation 12.71 |
| BHR-100 | Short Form (36) Health Survey (SF-36) | Physical Composite Summary - Month 3 | 39.8 score on a scale | Standard Deviation 12.16 |
| BHR-100 | Short Form (36) Health Survey (SF-36) | Mental Composite Summary - Month 6 | 47.9 score on a scale | Standard Deviation 11.24 |
| BHR-100 | Short Form (36) Health Survey (SF-36) | Physical Composite Summary - Month 6 | 44.6 score on a scale | Standard Deviation 11.5 |
| Placebo | Short Form (36) Health Survey (SF-36) | Mental Composite Summary - Month 6 | 46.8 score on a scale | Standard Deviation 12.36 |
| Placebo | Short Form (36) Health Survey (SF-36) | Mental Composite Summary - Month 3 | 48.5 score on a scale | Standard Deviation 12.72 |
| Placebo | Short Form (36) Health Survey (SF-36) | Physical Composite Summary - Month 6 | 45.1 score on a scale | Standard Deviation 11.3 |
| Placebo | Short Form (36) Health Survey (SF-36) | Physical Composite Summary - Month 3 | 40.6 score on a scale | Standard Deviation 11.37 |