Trial Outcomes & Findings for Brain Tissue Oxygen Monitoring in Traumatic Brain Injury (TBI) (NCT NCT00974259)
NCT ID: NCT00974259
Last Updated: 2019-09-26
Results Overview
Proportion of time PbtO2 below 20 mm Hg
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
122 participants
Primary outcome timeframe
5 days
Results posted on
2019-09-26
Participant Flow
Patients with severe TBI who required ICP monitoring were screened at 10 Level 1 trauma centers . Patients admitted with an initial GCS greater than 8 who deteriorated neurologically (within 48 hr of injury) from a presumptive could also be enrolled provided randomization and ICP monitor placement occurred within 12 hours of deterioration.
Participant milestones
| Measure |
pBrO2 and ICP Management
Treatment protocol based on pBrO2 and ICP values.
Management protocol based on pBrO2 and ICP values.: For patients who experience falls in pBrO2 below 20 mm Hg, a hierarchical treatment algorithm will be instituted, adapted from published recommendations49. In principle, episodes requiring therapy will fall into one of 4 scenarios (scenario A, B, C, and D, defined in figure 7), which will require different management strategies. The treatment protocol depends on which type of episode is being treated. Treatment is triggered by abnormalities in either ICP (\> 20 mm Hg) or pBrO2 (\< 20 mm Hg) are noted. Elevations in ICP above 20 mm Hg or decline in pBrO2 below 20 mm Hg for more than 5 minutes will trigger a treatment intervention. Treatment is directed to an episode. Patients may start in one type of episode and move to another. Therapy will depend on which type of episode they are in at any given time.
|
ICP Management
Treatment protocol based on ICP values only.
Management protocol based on ICP values only.: For the patients randomized to ICP treatment alone, only Scenario A and Scenario B episodes are relevant.
|
|---|---|---|
|
Overall Study
STARTED
|
59
|
63
|
|
Overall Study
COMPLETED
|
57
|
62
|
|
Overall Study
NOT COMPLETED
|
2
|
1
|
Reasons for withdrawal
| Measure |
pBrO2 and ICP Management
Treatment protocol based on pBrO2 and ICP values.
Management protocol based on pBrO2 and ICP values.: For patients who experience falls in pBrO2 below 20 mm Hg, a hierarchical treatment algorithm will be instituted, adapted from published recommendations49. In principle, episodes requiring therapy will fall into one of 4 scenarios (scenario A, B, C, and D, defined in figure 7), which will require different management strategies. The treatment protocol depends on which type of episode is being treated. Treatment is triggered by abnormalities in either ICP (\> 20 mm Hg) or pBrO2 (\< 20 mm Hg) are noted. Elevations in ICP above 20 mm Hg or decline in pBrO2 below 20 mm Hg for more than 5 minutes will trigger a treatment intervention. Treatment is directed to an episode. Patients may start in one type of episode and move to another. Therapy will depend on which type of episode they are in at any given time.
|
ICP Management
Treatment protocol based on ICP values only.
Management protocol based on ICP values only.: For the patients randomized to ICP treatment alone, only Scenario A and Scenario B episodes are relevant.
|
|---|---|---|
|
Overall Study
Technically inadequate PbtO2 recordings
|
2
|
1
|
Baseline Characteristics
Brain Tissue Oxygen Monitoring in Traumatic Brain Injury (TBI)
Baseline characteristics by cohort
| Measure |
pBrO2 and ICP Management
n=57 Participants
Treatment protocol based on pBrO2 and ICP values.
Management protocol based on pBrO2 and ICP values.: For patients who experience falls in pBrO2 below 20 mm Hg, a hierarchical treatment algorithm will be instituted, adapted from published recommendations49. In principle, episodes requiring therapy will fall into one of 4 scenarios (scenario A, B, C, and D, defined in figure 7), which will require different management strategies. The treatment protocol depends on which type of episode is being treated. Treatment is triggered by abnormalities in either ICP (\> 20 mm Hg) or pBrO2 (\< 20 mm Hg) are noted. Elevations in ICP above 20 mm Hg or decline in pBrO2 below 20 mm Hg for more than 5 minutes will trigger a treatment intervention. Treatment is directed to an episode. Patients may start in one type of episode and move to another. Therapy will depend on which type of episode they are in at any given time.
|
ICP Management
n=62 Participants
Treatment protocol based on ICP values only.
Management protocol based on ICP values only.: For the patients randomized to ICP treatment alone, only Scenario A and Scenario B episodes are relevant.
|
Total
n=119 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
57 Participants
n=5 Participants
|
62 Participants
n=7 Participants
|
119 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
37.8 years
STANDARD_DEVIATION 17.2 • n=5 Participants
|
36.2 years
STANDARD_DEVIATION 17.5 • n=7 Participants
|
37.0 years
STANDARD_DEVIATION 17.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
46 Participants
n=5 Participants
|
46 Participants
n=7 Participants
|
92 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
47 Participants
n=5 Participants
|
53 Participants
n=7 Participants
|
100 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
9 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Unknown
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Injury Type--Closed Head Injury
|
56 Participants
n=5 Participants
|
62 Participants
n=7 Participants
|
118 Participants
n=5 Participants
|
|
Glasgow Come Scale-Motor
|
3.6 units on a scale
STANDARD_DEVIATION 1.5 • n=5 Participants
|
3.7 units on a scale
STANDARD_DEVIATION 1.5 • n=7 Participants
|
3.7 units on a scale
STANDARD_DEVIATION 1.5 • n=5 Participants
|
|
Craniectomy
|
12 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 5 daysProportion of time PbtO2 below 20 mm Hg
Outcome measures
| Measure |
pBrO2 and ICP Management
n=57 Participants
Treatment protocol based on pBrO2 and ICP values.
Management protocol based on pBrO2 and ICP values.: For patients who experience falls in pBrO2 below 20 mm Hg, a hierarchical treatment algorithm will be instituted, adapted from published recommendations49. In principle, episodes requiring therapy will fall into one of 4 scenarios (scenario A, B, C, and D, defined in figure 7), which will require different management strategies. The treatment protocol depends on which type of episode is being treated. Treatment is triggered by abnormalities in either ICP (\> 20 mm Hg) or pBrO2 (\< 20 mm Hg) are noted. Elevations in ICP above 20 mm Hg or decline in pBrO2 below 20 mm Hg for more than 5 minutes will trigger a treatment intervention. Treatment is directed to an episode. Patients may start in one type of episode and move to another. Therapy will depend on which type of episode they are in at any given time.
|
ICP Management
n=62 Participants
Treatment protocol based on ICP values only.
Management protocol based on ICP values only.: For the patients randomized to ICP treatment alone, only Scenario A and Scenario B episodes are relevant.
|
|---|---|---|
|
Fraction of Time That Brain Oxygen Levels Are Below the Critical Threshold of 20 mm Hg .
|
0.15 Proportion
Standard Deviation 0.21
|
0.44 Proportion
Standard Deviation 0.31
|
SECONDARY outcome
Timeframe: 5 daysTotal number participants with PbtO2 directed intervention-related Serious Adverse Events
Outcome measures
| Measure |
pBrO2 and ICP Management
n=57 Participants
Treatment protocol based on pBrO2 and ICP values.
Management protocol based on pBrO2 and ICP values.: For patients who experience falls in pBrO2 below 20 mm Hg, a hierarchical treatment algorithm will be instituted, adapted from published recommendations49. In principle, episodes requiring therapy will fall into one of 4 scenarios (scenario A, B, C, and D, defined in figure 7), which will require different management strategies. The treatment protocol depends on which type of episode is being treated. Treatment is triggered by abnormalities in either ICP (\> 20 mm Hg) or pBrO2 (\< 20 mm Hg) are noted. Elevations in ICP above 20 mm Hg or decline in pBrO2 below 20 mm Hg for more than 5 minutes will trigger a treatment intervention. Treatment is directed to an episode. Patients may start in one type of episode and move to another. Therapy will depend on which type of episode they are in at any given time.
|
ICP Management
n=62 Participants
Treatment protocol based on ICP values only.
Management protocol based on ICP values only.: For the patients randomized to ICP treatment alone, only Scenario A and Scenario B episodes are relevant.
|
|---|---|---|
|
Total Number Participants With Adverse Events Associated With PbtO2 Monitoring.
Cardiovascular SAEs
|
9 participants
|
8 participants
|
|
Total Number Participants With Adverse Events Associated With PbtO2 Monitoring.
Gastro-intestinal SAEs
|
1 participants
|
1 participants
|
|
Total Number Participants With Adverse Events Associated With PbtO2 Monitoring.
Neurological SAEs
|
5 participants
|
10 participants
|
|
Total Number Participants With Adverse Events Associated With PbtO2 Monitoring.
Respiratory SEAs
|
4 participants
|
1 participants
|
|
Total Number Participants With Adverse Events Associated With PbtO2 Monitoring.
Other SAEs
|
8 participants
|
17 participants
|
|
Total Number Participants With Adverse Events Associated With PbtO2 Monitoring.
Death Following withdrawal of medical care
|
8 participants
|
14 participants
|
SECONDARY outcome
Timeframe: 5 daysNumber of protocol deviations and violations for ICP/PbtO2 group and ICP only group. The unit of measure for this outcome is number of events, where an event can be either a deviation or a violation.
Outcome measures
| Measure |
pBrO2 and ICP Management
n=57 Participants
Treatment protocol based on pBrO2 and ICP values.
Management protocol based on pBrO2 and ICP values.: For patients who experience falls in pBrO2 below 20 mm Hg, a hierarchical treatment algorithm will be instituted, adapted from published recommendations49. In principle, episodes requiring therapy will fall into one of 4 scenarios (scenario A, B, C, and D, defined in figure 7), which will require different management strategies. The treatment protocol depends on which type of episode is being treated. Treatment is triggered by abnormalities in either ICP (\> 20 mm Hg) or pBrO2 (\< 20 mm Hg) are noted. Elevations in ICP above 20 mm Hg or decline in pBrO2 below 20 mm Hg for more than 5 minutes will trigger a treatment intervention. Treatment is directed to an episode. Patients may start in one type of episode and move to another. Therapy will depend on which type of episode they are in at any given time.
|
ICP Management
n=62 Participants
Treatment protocol based on ICP values only.
Management protocol based on ICP values only.: For the patients randomized to ICP treatment alone, only Scenario A and Scenario B episodes are relevant.
|
|---|---|---|
|
Adherence to PbtO2 and ICP-directed Treatment Protocol
Deviation: ICP 20-25 for > 30 min w/o Rx
|
95 Events (sum of deviations & violations)
|
71 Events (sum of deviations & violations)
|
|
Adherence to PbtO2 and ICP-directed Treatment Protocol
Deviation: PbtO2 15-19 for > 30 min w/o Rx
|
24 Events (sum of deviations & violations)
|
0 Events (sum of deviations & violations)
|
|
Adherence to PbtO2 and ICP-directed Treatment Protocol
Violation: ICP > 25 for > 30 min w/o Rx
|
7 Events (sum of deviations & violations)
|
14 Events (sum of deviations & violations)
|
|
Adherence to PbtO2 and ICP-directed Treatment Protocol
Violation: PbtO2 < 15 for > 30 min w/o Rx
|
17 Events (sum of deviations & violations)
|
0 Events (sum of deviations & violations)
|
SECONDARY outcome
Timeframe: 6 monthsDichotomized Glagow Outcome Score-Extended: GOSE 1-4 = Poor Outcome GOSE 5-8 = Good Outcome GOSE is a 8-point scale, with 1 = death, 8 = full recovery.
Outcome measures
| Measure |
pBrO2 and ICP Management
n=57 Participants
Treatment protocol based on pBrO2 and ICP values.
Management protocol based on pBrO2 and ICP values.: For patients who experience falls in pBrO2 below 20 mm Hg, a hierarchical treatment algorithm will be instituted, adapted from published recommendations49. In principle, episodes requiring therapy will fall into one of 4 scenarios (scenario A, B, C, and D, defined in figure 7), which will require different management strategies. The treatment protocol depends on which type of episode is being treated. Treatment is triggered by abnormalities in either ICP (\> 20 mm Hg) or pBrO2 (\< 20 mm Hg) are noted. Elevations in ICP above 20 mm Hg or decline in pBrO2 below 20 mm Hg for more than 5 minutes will trigger a treatment intervention. Treatment is directed to an episode. Patients may start in one type of episode and move to another. Therapy will depend on which type of episode they are in at any given time.
|
ICP Management
n=62 Participants
Treatment protocol based on ICP values only.
Management protocol based on ICP values only.: For the patients randomized to ICP treatment alone, only Scenario A and Scenario B episodes are relevant.
|
|---|---|---|
|
Relative Risk of Good Outcome of ICP/PbtO2 Group Compared to ICP Only Group.
GOSE 1
|
13 participants
|
18 participants
|
|
Relative Risk of Good Outcome of ICP/PbtO2 Group Compared to ICP Only Group.
GOSE 2
|
1 participants
|
2 participants
|
|
Relative Risk of Good Outcome of ICP/PbtO2 Group Compared to ICP Only Group.
GOSE 3
|
7 participants
|
5 participants
|
|
Relative Risk of Good Outcome of ICP/PbtO2 Group Compared to ICP Only Group.
GOSE 4
|
10 participants
|
12 participants
|
|
Relative Risk of Good Outcome of ICP/PbtO2 Group Compared to ICP Only Group.
GOSE 5
|
4 participants
|
4 participants
|
|
Relative Risk of Good Outcome of ICP/PbtO2 Group Compared to ICP Only Group.
GOSE 6
|
5 participants
|
5 participants
|
|
Relative Risk of Good Outcome of ICP/PbtO2 Group Compared to ICP Only Group.
GOSE 7
|
6 participants
|
4 participants
|
|
Relative Risk of Good Outcome of ICP/PbtO2 Group Compared to ICP Only Group.
GOSE 8
|
7 participants
|
2 participants
|
Adverse Events
pBrO2 and ICP Management
Serious events: 27 serious events
Other events: 48 other events
Deaths: 13 deaths
ICP Management
Serious events: 34 serious events
Other events: 55 other events
Deaths: 18 deaths
Serious adverse events
| Measure |
pBrO2 and ICP Management
n=57 participants at risk
Treatment protocol based on pBrO2 and ICP values.
Management protocol based on pBrO2 and ICP values.: For patients who experience falls in pBrO2 below 20 mm Hg, a hierarchical treatment algorithm will be instituted, adapted from published recommendations49. In principle, episodes requiring therapy will fall into one of 4 scenarios (scenario A, B, C, and D, defined in figure 7), which will require different management strategies. The treatment protocol depends on which type of episode is being treated. Treatment is triggered by abnormalities in either ICP (\> 20 mm Hg) or pBrO2 (\< 20 mm Hg) are noted. Elevations in ICP above 20 mm Hg or decline in pBrO2 below 20 mm Hg for more than 5 minutes will trigger a treatment intervention. Treatment is directed to an episode. Patients may start in one type of episode and move to another. Therapy will depend on which type of episode they are in at any given time.
|
ICP Management
n=62 participants at risk
Treatment protocol based on ICP values only.
Management protocol based on ICP values only.: For the patients randomized to ICP treatment alone, only Scenario A and Scenario B episodes are relevant.
|
|---|---|---|
|
Cardiac disorders
Cardiovascular
|
15.8%
9/57 • Number of events 9
|
8.1%
5/62 • Number of events 5
|
|
General disorders
Pulmonary
|
7.0%
4/57 • Number of events 4
|
1.6%
1/62 • Number of events 1
|
|
Gastrointestinal disorders
Gastro-intestinal
|
1.8%
1/57 • Number of events 1
|
1.6%
1/62 • Number of events 1
|
|
Nervous system disorders
Neurological
|
8.8%
5/57 • Number of events 5
|
16.1%
10/62 • Number of events 10
|
|
General disorders
Other
|
14.0%
8/57 • Number of events 8
|
27.4%
17/62 • Number of events 17
|
Other adverse events
| Measure |
pBrO2 and ICP Management
n=57 participants at risk
Treatment protocol based on pBrO2 and ICP values.
Management protocol based on pBrO2 and ICP values.: For patients who experience falls in pBrO2 below 20 mm Hg, a hierarchical treatment algorithm will be instituted, adapted from published recommendations49. In principle, episodes requiring therapy will fall into one of 4 scenarios (scenario A, B, C, and D, defined in figure 7), which will require different management strategies. The treatment protocol depends on which type of episode is being treated. Treatment is triggered by abnormalities in either ICP (\> 20 mm Hg) or pBrO2 (\< 20 mm Hg) are noted. Elevations in ICP above 20 mm Hg or decline in pBrO2 below 20 mm Hg for more than 5 minutes will trigger a treatment intervention. Treatment is directed to an episode. Patients may start in one type of episode and move to another. Therapy will depend on which type of episode they are in at any given time.
|
ICP Management
n=62 participants at risk
Treatment protocol based on ICP values only.
Management protocol based on ICP values only.: For the patients randomized to ICP treatment alone, only Scenario A and Scenario B episodes are relevant.
|
|---|---|---|
|
General disorders
Other
|
84.2%
48/57 • Number of events 48
|
88.7%
55/62 • Number of events 55
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place