Trial Outcomes & Findings for Efficacy and Safety Study of Intravenous Progesterone in Patients With Severe Traumatic Brain Injury (NCT NCT01143064)
NCT ID: NCT01143064
Last Updated: 2024-10-02
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
1195 participants
Primary outcome timeframe
6 months
Results posted on
2024-10-02
Participant Flow
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
597
|
598
|
|
Overall Study
COMPLETED
|
464
|
483
|
|
Overall Study
NOT COMPLETED
|
133
|
115
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
Death
|
109
|
91
|
|
Overall Study
Adverse Event
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
7
|
5
|
|
Overall Study
Lost to Follow-up
|
17
|
14
|
|
Overall Study
Physician Decision
|
0
|
4
|
Baseline Characteristics
Efficacy and Safety Study of Intravenous Progesterone in Patients With Severe Traumatic Brain Injury
Baseline characteristics by cohort
| Measure |
BHR-100
n=591 Participants
Progesterone: Intravenous administration of 0.71mg/kg/hr for 1hr followed by 0.5mg/kg/hr administered intravenously for an additional 119 hrs.
|
Placebo
n=588 Participants
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.
|
Total
n=1179 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
37.3 years
STANDARD_DEVIATION 15.60 • n=5 Participants
|
37.6 years
STANDARD_DEVIATION 15.36 • n=7 Participants
|
37.4 years
STANDARD_DEVIATION 15.47 • n=5 Participants
|
|
Sex: Female, Male
Female
|
127 Participants
n=5 Participants
|
125 Participants
n=7 Participants
|
252 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
464 Participants
n=5 Participants
|
463 Participants
n=7 Participants
|
927 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
61 Participants
n=5 Participants
|
60 Participants
n=7 Participants
|
121 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
479 Participants
n=5 Participants
|
487 Participants
n=7 Participants
|
966 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
51 Participants
n=5 Participants
|
41 Participants
n=7 Participants
|
92 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
441 Participants
n=5 Participants
|
458 Participants
n=7 Participants
|
899 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black/African American/African Heritage
|
23 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian/other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
63 Participants
n=5 Participants
|
63 Participants
n=7 Participants
|
126 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Allowed to Obtain
|
51 Participants
n=5 Participants
|
41 Participants
n=7 Participants
|
92 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
11 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Region of Enrollment
Argentina
|
31 participants
n=5 Participants
|
33 participants
n=7 Participants
|
64 participants
n=5 Participants
|
|
Region of Enrollment
Romania
|
5 participants
n=5 Participants
|
1 participants
n=7 Participants
|
6 participants
n=5 Participants
|
|
Region of Enrollment
Singapore
|
6 participants
n=5 Participants
|
9 participants
n=7 Participants
|
15 participants
n=5 Participants
|
|
Region of Enrollment
Hungary
|
3 participants
n=5 Participants
|
5 participants
n=7 Participants
|
8 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
219 participants
n=5 Participants
|
220 participants
n=7 Participants
|
439 participants
n=5 Participants
|
|
Region of Enrollment
Czechia
|
24 participants
n=5 Participants
|
34 participants
n=7 Participants
|
58 participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
24 participants
n=5 Participants
|
30 participants
n=7 Participants
|
54 participants
n=5 Participants
|
|
Region of Enrollment
Malaysia
|
11 participants
n=5 Participants
|
8 participants
n=7 Participants
|
19 participants
n=5 Participants
|
|
Region of Enrollment
Thailand
|
22 participants
n=5 Participants
|
24 participants
n=7 Participants
|
46 participants
n=5 Participants
|
|
Region of Enrollment
Russia
|
6 participants
n=5 Participants
|
7 participants
n=7 Participants
|
13 participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
42 participants
n=5 Participants
|
51 participants
n=7 Participants
|
93 participants
n=5 Participants
|
|
Region of Enrollment
Austria
|
18 participants
n=5 Participants
|
14 participants
n=7 Participants
|
32 participants
n=5 Participants
|
|
Region of Enrollment
Netherlands
|
2 participants
n=5 Participants
|
5 participants
n=7 Participants
|
7 participants
n=5 Participants
|
|
Region of Enrollment
Belgium
|
16 participants
n=5 Participants
|
13 participants
n=7 Participants
|
29 participants
n=5 Participants
|
|
Region of Enrollment
China
|
20 participants
n=5 Participants
|
15 participants
n=7 Participants
|
35 participants
n=5 Participants
|
|
Region of Enrollment
Finland
|
5 participants
n=5 Participants
|
1 participants
n=7 Participants
|
6 participants
n=5 Participants
|
|
Region of Enrollment
Taiwan
|
3 participants
n=5 Participants
|
2 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
22 participants
n=5 Participants
|
24 participants
n=7 Participants
|
46 participants
n=5 Participants
|
|
Region of Enrollment
Israel
|
37 participants
n=5 Participants
|
25 participants
n=7 Participants
|
62 participants
n=5 Participants
|
|
Region of Enrollment
France
|
51 participants
n=5 Participants
|
41 participants
n=7 Participants
|
92 participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
24 participants
n=5 Participants
|
26 participants
n=7 Participants
|
50 participants
n=5 Participants
|
|
Glasgow Coma Score Motor Score
1-2
|
129 Participants
n=5 Participants
|
167 Participants
n=7 Participants
|
296 Participants
n=5 Participants
|
|
Glasgow Coma Score Motor Score
3
|
84 Participants
n=5 Participants
|
74 Participants
n=7 Participants
|
158 Participants
n=5 Participants
|
|
Glasgow Coma Score Motor Score
4
|
167 Participants
n=5 Participants
|
160 Participants
n=7 Participants
|
327 Participants
n=5 Participants
|
|
Glasgow Coma Score Motor Score
5-6
|
209 Participants
n=5 Participants
|
185 Participants
n=7 Participants
|
394 Participants
n=5 Participants
|
|
Glasgow Coma Score Motor Score
Missing
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Pupillary Response
Bilateral
|
480 Participants
n=5 Participants
|
475 Participants
n=7 Participants
|
955 Participants
n=5 Participants
|
|
Pupillary Response
Unilateral
|
109 Participants
n=5 Participants
|
107 Participants
n=7 Participants
|
216 Participants
n=5 Participants
|
|
Pupillary Response
No Reactive Pupils
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Pupillary Response
Not Testable
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Pupillary Response
Missing
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Hypoxia
Yes
|
15 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Hypoxia
No
|
523 Participants
n=5 Participants
|
521 Participants
n=7 Participants
|
1044 Participants
n=5 Participants
|
|
Hypoxia
Suspected
|
37 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
69 Participants
n=5 Participants
|
|
Hypoxia
Unknown
|
16 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
|
Hypotension
Yes
|
85 Participants
n=5 Participants
|
66 Participants
n=7 Participants
|
151 Participants
n=5 Participants
|
|
Hypotension
No
|
484 Participants
n=5 Participants
|
498 Participants
n=7 Participants
|
982 Participants
n=5 Participants
|
|
Hypotension
Suspected
|
8 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Hypotension
Unknown
|
14 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Marshall CT Classification
I
|
6 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Marshall CT Classification
II
|
235 Participants
n=5 Participants
|
233 Participants
n=7 Participants
|
468 Participants
n=5 Participants
|
|
Marshall CT Classification
III
|
178 Participants
n=5 Participants
|
164 Participants
n=7 Participants
|
342 Participants
n=5 Participants
|
|
Marshall CT Classification
IV
|
35 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
70 Participants
n=5 Participants
|
|
Marshall CT Classification
Evacuated/Non-Evacuated Mass Lesion
|
134 Participants
n=5 Participants
|
151 Participants
n=7 Participants
|
285 Participants
n=5 Participants
|
|
Marshall CT Classification
Missing
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Traumatic Subarachnoid Hemorrhage
Yes
|
449 Participants
n=5 Participants
|
456 Participants
n=7 Participants
|
905 Participants
n=5 Participants
|
|
Traumatic Subarachnoid Hemorrhage
No
|
138 Participants
n=5 Participants
|
131 Participants
n=7 Participants
|
269 Participants
n=5 Participants
|
|
Traumatic Subarachnoid Hemorrhage
Missing
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 6 monthsPopulation: 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.
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.
Outcome measures
| Measure |
BHR-100
n=591 Participants
Progesterone: Intravenous administration of 0.71mg/kg/hr for 1hr followed by 0.5mg/kg/hr administered intravenously for an additional 119 hrs.
|
Placebo
n=588 Participants
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.
|
|---|---|---|
|
Glasgow Outcome Scale (GOS)
Good Recovery
|
189 Participants
|
183 Participants
|
|
Glasgow Outcome Scale (GOS)
Moderate Disability
|
109 Participants
|
114 Participants
|
|
Glasgow Outcome Scale (GOS)
Severe Disability
|
162 Participants
|
160 Participants
|
|
Glasgow Outcome Scale (GOS)
Vegetative State/Dead
|
131 Participants
|
131 Participants
|
SECONDARY outcome
Timeframe: 1 month post injuryPopulation: P-value population size is based on the number of subjects with status = alive or dead, month 6 within the mITT population.
The mortality rate at one month will be compared between the two treatment groups.
Outcome measures
| Measure |
BHR-100
n=591 Participants
Progesterone: Intravenous administration of 0.71mg/kg/hr for 1hr followed by 0.5mg/kg/hr administered intravenously for an additional 119 hrs.
|
Placebo
n=588 Participants
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.
|
|---|---|---|
|
Mortality at Month 1
Lost to Follow-up
|
0 Participants
|
0 Participants
|
|
Mortality at Month 1
Consent Withdrawn
|
0 Participants
|
0 Participants
|
|
Mortality at Month 1
Alive
|
500 Participants
|
507 Participants
|
|
Mortality at Month 1
Dead
|
87 Participants
|
74 Participants
|
|
Mortality at Month 1
Other
|
1 Participants
|
0 Participants
|
|
Mortality at Month 1
Missing
|
3 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: 6 months post injuryPopulation: P-value population size is based on the number of subjects with status = alive or dead, month 6 within the mITT population.
The mortality rate at six months will be compared between the two treatment groups.
Outcome measures
| Measure |
BHR-100
n=591 Participants
Progesterone: Intravenous administration of 0.71mg/kg/hr for 1hr followed by 0.5mg/kg/hr administered intravenously for an additional 119 hrs.
|
Placebo
n=588 Participants
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.
|
|---|---|---|
|
Mortality at Month 6
Lost to Follow-up
|
0 Participants
|
2 Participants
|
|
Mortality at Month 6
Consent Withdrawn
|
0 Participants
|
0 Participants
|
|
Mortality at Month 6
Alive
|
463 Participants
|
472 Participants
|
|
Mortality at Month 6
Dead
|
109 Participants
|
95 Participants
|
|
Mortality at Month 6
Other
|
0 Participants
|
0 Participants
|
|
Mortality at Month 6
Missing
|
19 Participants
|
19 Participants
|
SECONDARY outcome
Timeframe: Month 3The 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.
Outcome measures
| Measure |
BHR-100
n=591 Participants
Progesterone: Intravenous administration of 0.71mg/kg/hr for 1hr followed by 0.5mg/kg/hr administered intravenously for an additional 119 hrs.
|
Placebo
n=588 Participants
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.
|
|---|---|---|
|
Glasgow Outcome Scale at 3 Months
Good Recovery
|
103 Participants
|
101 Participants
|
|
Glasgow Outcome Scale at 3 Months
Moderate Disability
|
103 Participants
|
114 Participants
|
|
Glasgow Outcome Scale at 3 Months
Severe Disability
|
224 Participants
|
216 Participants
|
|
Glasgow Outcome Scale at 3 Months
Vegetative State
|
33 Participants
|
49 Participants
|
|
Glasgow Outcome Scale at 3 Months
Dead
|
102 Participants
|
88 Participants
|
|
Glasgow Outcome Scale at 3 Months
Missing
|
26 Participants
|
20 Participants
|
SECONDARY outcome
Timeframe: 3 months and 6 months post injuryPopulation: 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.
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
Outcome measures
| Measure |
BHR-100
n=565 Participants
Progesterone: Intravenous administration of 0.71mg/kg/hr for 1hr followed by 0.5mg/kg/hr administered intravenously for an additional 119 hrs.
|
Placebo
n=568 Participants
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.
|
|---|---|---|
|
Glasgow Outcome Scale - Extended (GOS-E)
Vegetative State - 3 months
|
33 Participants
|
49 Participants
|
|
Glasgow Outcome Scale - Extended (GOS-E)
Upper Moderate Disability - 3 months
|
68 Participants
|
80 Participants
|
|
Glasgow Outcome Scale - Extended (GOS-E)
Lower Severe Disability - 6 months
|
115 Participants
|
109 Participants
|
|
Glasgow Outcome Scale - Extended (GOS-E)
Upper Severe Disability - 6 months
|
37 Participants
|
44 Participants
|
|
Glasgow Outcome Scale - Extended (GOS-E)
Upper Good Recovery - 6 months
|
108 Participants
|
109 Participants
|
|
Glasgow Outcome Scale - Extended (GOS-E)
Dead - 3 months
|
102 Participants
|
88 Participants
|
|
Glasgow Outcome Scale - Extended (GOS-E)
Lower Severe Disability - 3 months
|
173 Participants
|
165 Participants
|
|
Glasgow Outcome Scale - Extended (GOS-E)
Upper Severe Disability - 3 months
|
51 Participants
|
51 Participants
|
|
Glasgow Outcome Scale - Extended (GOS-E)
Lower Moderate Disability - 3 months
|
35 Participants
|
34 Participants
|
|
Glasgow Outcome Scale - Extended (GOS-E)
Lower Good Recovery - 3 months
|
53 Participants
|
46 Participants
|
|
Glasgow Outcome Scale - Extended (GOS-E)
Upper Good Recovery - 3 months
|
50 Participants
|
55 Participants
|
|
Glasgow Outcome Scale - Extended (GOS-E)
Dead - 6 months
|
109 Participants
|
95 Participants
|
|
Glasgow Outcome Scale - Extended (GOS-E)
Vegetative State - 6 months
|
20 Participants
|
33 Participants
|
|
Glasgow Outcome Scale - Extended (GOS-E)
Lower Moderate Disability - 6 months
|
36 Participants
|
38 Participants
|
|
Glasgow Outcome Scale - Extended (GOS-E)
Upper Moderate Disability - 6 months
|
70 Participants
|
72 Participants
|
|
Glasgow Outcome Scale - Extended (GOS-E)
Lower Good Recovery - 6 months
|
71 Participants
|
64 Participants
|
SECONDARY outcome
Timeframe: 3 months and 6 months post injuryPopulation: Only participants with data for these parameters have been included.
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.
Outcome measures
| Measure |
BHR-100
n=354 Participants
Progesterone: Intravenous administration of 0.71mg/kg/hr for 1hr followed by 0.5mg/kg/hr administered intravenously for an additional 119 hrs.
|
Placebo
n=369 Participants
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.
|
|---|---|---|
|
Short Form (36) Health Survey (SF-36)
Mental Composite Summary - Month 3
|
48.7 score on a scale
Standard Deviation 12.71
|
48.5 score on a scale
Standard Deviation 12.72
|
|
Short Form (36) Health Survey (SF-36)
Physical Composite Summary - Month 3
|
39.8 score on a scale
Standard Deviation 12.16
|
40.6 score on a scale
Standard Deviation 11.37
|
|
Short Form (36) Health Survey (SF-36)
Physical Composite Summary - Month 6
|
44.6 score on a scale
Standard Deviation 11.50
|
45.1 score on a scale
Standard Deviation 11.30
|
|
Short Form (36) Health Survey (SF-36)
Mental Composite Summary - Month 6
|
47.9 score on a scale
Standard Deviation 11.24
|
46.8 score on a scale
Standard Deviation 12.36
|
SECONDARY outcome
Timeframe: Admission through post-infusion Day 6Population: Only participants with data for these parameters have been included.
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.
Outcome measures
| Measure |
BHR-100
n=591 Participants
Progesterone: Intravenous administration of 0.71mg/kg/hr for 1hr followed by 0.5mg/kg/hr administered intravenously for an additional 119 hrs.
|
Placebo
n=588 Participants
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.
|
|---|---|---|
|
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
|
155 Participants
|
|
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
|
460 Participants
|
|
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
|
523 Participants
|
|
Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL)
Hypothermia (TIL)
|
61 Participants
|
69 Participants
|
|
Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL)
Pressor Administered (TIL)
|
315 Participants
|
343 Participants
|
|
Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL)
Hypertonic Saline (TIL)
|
225 Participants
|
233 Participants
|
|
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
|
299 Participants
|
|
Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL)
Surgical Decompression (TIL)
|
192 Participants
|
174 Participants
|
|
Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL)
Barbiturate Induced Coma (TIL)
|
82 Participants
|
73 Participants
|
|
Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL)
Hyperventilation (TIL)
|
78 Participants
|
68 Participants
|
|
Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL)
Mannitol (TIL)
|
288 Participants
|
285 Participants
|
|
Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL)
Ventricular Drainage (TIL)
|
198 Participants
|
208 Participants
|
|
Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL)
Paralysis Induction (TIL)
|
220 Participants
|
231 Participants
|
|
Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL)
Sedation (TIL)
|
565 Participants
|
565 Participants
|
Adverse Events
BHR-100
Serious events: 224 serious events
Other events: 265 other events
Deaths: 109 deaths
Placebo
Serious events: 214 serious events
Other events: 286 other events
Deaths: 95 deaths
Serious adverse events
| Measure |
BHR-100
n=596 participants at risk
Progesterone: Intravenous administration of 0.71mg/kg/hr for 1hr followed by 0.5mg/kg/hr administered intravenously for an additional 119 hrs.
|
Placebo
n=583 participants at risk
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.
|
|---|---|---|
|
Nervous system disorders
Intracranial pressure increased
|
5.0%
30/596
|
4.6%
27/583
|
|
Nervous system disorders
Brain oedema
|
3.2%
19/596
|
2.9%
17/583
|
|
Nervous system disorders
Hydrocephalus
|
2.0%
12/596
|
2.4%
14/583
|
|
Nervous system disorders
Convulsion
|
1.5%
9/596
|
0.51%
3/583
|
|
Nervous system disorders
Cerebral infarction
|
1.3%
8/596
|
0.86%
5/583
|
|
Infections and infestations
Pneumonia
|
6.4%
38/596
|
6.9%
40/583
|
|
Infections and infestations
Sepsis
|
2.5%
15/596
|
2.4%
14/583
|
|
Infections and infestations
Septic shock
|
1.8%
11/596
|
1.2%
7/583
|
|
Infections and infestations
Meningitis
|
1.2%
7/596
|
0.86%
5/583
|
|
Injury, poisoning and procedural complications
Brain herniation
|
2.5%
15/596
|
2.2%
13/583
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
1.7%
10/596
|
0.86%
5/583
|
|
Injury, poisoning and procedural complications
Brain contusion
|
0.84%
5/596
|
1.0%
6/583
|
|
Injury, poisoning and procedural complications
Traumatic brain injury
|
0.67%
4/596
|
1.7%
10/583
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
1.2%
7/596
|
1.0%
6/583
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
1.0%
6/596
|
1.2%
7/583
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.84%
5/596
|
1.5%
9/583
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.67%
4/596
|
1.9%
11/583
|
|
Cardiac disorders
Cardiac arrest
|
1.2%
7/596
|
0.51%
3/583
|
|
Cardiac disorders
Cardio-respiratory arrest
|
1.0%
6/596
|
0.86%
5/583
|
|
Cardiac disorders
Multi-organ failure
|
1.0%
6/596
|
1.2%
7/583
|
Other adverse events
| Measure |
BHR-100
n=596 participants at risk
Progesterone: Intravenous administration of 0.71mg/kg/hr for 1hr followed by 0.5mg/kg/hr administered intravenously for an additional 119 hrs.
|
Placebo
n=583 participants at risk
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.
|
|---|---|---|
|
General disorders
Pyrexia
|
35.1%
209/596
|
39.3%
229/583
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
15.8%
94/596
|
21.6%
126/583
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
14.4%
86/596
|
14.6%
85/583
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
9.9%
59/596
|
11.0%
64/583
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
5.4%
32/596
|
8.4%
49/583
|
|
Metabolism and nutrition disorders
Hypernatraemia
|
6.5%
39/596
|
5.7%
33/583
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
5.4%
32/596
|
8.4%
49/583
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
3.7%
22/596
|
5.0%
29/583
|
|
Vascular disorders
Hypertension
|
21.6%
129/596
|
21.8%
127/583
|
|
Vascular disorders
Hypotension
|
11.9%
71/596
|
13.7%
80/583
|
|
Blood and lymphatic system disorders
Anaemia
|
26.2%
156/596
|
27.3%
159/583
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
3.5%
21/596
|
5.5%
32/583
|
|
Gastrointestinal disorders
Constipation
|
16.3%
97/596
|
17.5%
102/583
|
|
Investigations
Gamma-glutamyltransferase increased
|
8.6%
51/596
|
6.0%
35/583
|
|
Investigations
Alanine aminotransferase increased
|
5.0%
30/596
|
3.1%
18/583
|
|
Cardiac disorders
Tachycardia
|
11.6%
69/596
|
10.8%
63/583
|
|
Psychiatric disorders
Agitation
|
13.3%
79/596
|
13.4%
78/583
|
|
Endocrine disorders
Diabetes insipidus
|
5.5%
33/596
|
7.4%
43/583
|
Additional Information
Global Chief Medical Officer
Besins Healthcare Ireland Ltd
Phone: +353 87 1039215
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place