Trial Outcomes & Findings for CENTER-TBI: Collaborative European NeuroTrauma Effectiveness Research in TBI (NCT NCT02210221)

NCT ID: NCT02210221

Last Updated: 2022-11-07

Results Overview

The Extended Glasgow Outcome Scale is a global scale for functional outcome that rates patient status into 8 categories, going from dead to good recovery. 1. Death 2. Vegetative sate 3. Lower severe disability 4. Upper severe disability 5. Lower moderate disability 6. Upper moderate disability - some disability but can potentially return to some form of employment 7. Lower good recovery - minor physical or mental defect 8. Upper good recovery - full recovery The 6-month GOSE score is available in 3804 patients (84%).

• Recruitment status: COMPLETED
• Target enrollment: 4559 participants
• Primary outcome timeframe: 6 months
• Results posted on: 2022-11-07

Participant Flow

CENTER-TBI is an observational cohort study. Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, are analysed in the core study: 848 (19%) patients were in the ER stratum, 1523 (34%) in the admission stratum, and 2138 (47%) in the ICU stratum.

Of 4559 patients in the core study, 4509 patients are available for analysis.

Participant milestones

Measure	CENTER-TBI Population Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study and from 22 782 patients in the registry. In the core study, 848 (19%) patients were in the ER stratum, 1523 (34%) in the admission stratum, and 2138 (47%) in the ICU stratum.
Overall Study STARTED	4559
Overall Study COMPLETED	4509
Overall Study NOT COMPLETED	50

Reasons for withdrawal

Measure	CENTER-TBI Population Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study and from 22 782 patients in the registry. In the core study, 848 (19%) patients were in the ER stratum, 1523 (34%) in the admission stratum, and 2138 (47%) in the ICU stratum.
Overall Study Lack of Efficacy	7
Overall Study Withdrawal by Subject	43

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	CENTER-TBI Population n=4509 Participants Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study.
Age, Continuous	50 years n=4509 Participants
Sex: Female, Male Female	1486 Participants n=4509 Participants
Sex: Female, Male Male	3023 Participants n=4509 Participants
Region of Enrollment Europe	4509 participants n=4509 Participants

PRIMARY outcome

Timeframe: 6 months

The Extended Glasgow Outcome Scale is a global scale for functional outcome that rates patient status into 8 categories, going from dead to good recovery.

1. Death

2. Vegetative sate

3. Lower severe disability

4. Upper severe disability

5. Lower moderate disability

6. Upper moderate disability - some disability but can potentially return to some form of employment

7. Lower good recovery - minor physical or mental defect

8. Upper good recovery - full recovery

The 6-month GOSE score is available in 3804 patients (84%).

Outcome measures

Measure	CENTER-TBI Population n=3804 Participants Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study.	ER Stratum n=694 Participants patients admitted to the ER	Admission Stratum n=1264 Participants patients admitted but not to the ICU	ICU Stratum n=1846 Participants patients admitted to the ICU
Glasgow Outcome Scale - Extended (GOSE) at 6 Months 6-month unfavourable outcome (GOSE <5)	966 Participants	31 Participants	140 Participants	795 Participants
Glasgow Outcome Scale - Extended (GOSE) at 6 Months 6-month GOSE <8	2419 Participants	207 Participants	665 Participants	1547 Participants

PRIMARY outcome

Timeframe: 6 months

The SF-12v2 Health Survey uses 12 questions to measure functional health and well-being from the patient's point of view. The SF-12v2 at 6 months is available in 2300 patients.

Outcome measures

Measure	CENTER-TBI Population n=2300 Participants Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study.	ER Stratum n=480 Participants patients admitted to the ER	Admission Stratum n=857 Participants patients admitted but not to the ICU	ICU Stratum n=963 Participants patients admitted to the ICU
SF-12v2 Health Survey (Short-Form Health Survey With 12 Questions) at 6 Months 6-month SF-12v2 physical component summary <40 (impaired)	661 Participants	112 Participants	207 Participants	342 Participants
SF-12v2 Health Survey (Short-Form Health Survey With 12 Questions) at 6 Months 6-month SF-12v2 mental component summary <40 (impaired)	551 Participants	101 Participants	184 Participants	266 Participants

PRIMARY outcome

Timeframe: 6 months

The Quality of Life in Brain Injury (Qolibri-OS) is a 6 item overall scale that provides a profile of health-related quality of life in domains typicality affected by brain injury, such as physical function, cognition, emotional status, ability to perform daily activities, personal life and social relationship, and satisfaction with current situation and future prospects.

The QOLIBRI scores are reported on a 0-100 scale , where 0=worst possible quality of life and 100=best possible quality of life.

Outcome measures

Measure	CENTER-TBI Population n=2323 Participants Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study.	ER Stratum n=474 Participants patients admitted to the ER	Admission Stratum n=866 Participants patients admitted but not to the ICU	ICU Stratum n=983 Participants patients admitted to the ICU
6 Month Quality of Life in Brain Injury (Qolibri-OS) <52 (Impaired)	511 Participants	91 Participants	160 Participants	260 Participants

SECONDARY outcome

Timeframe: 6 months

The PCL-5 is a self-report rating scale intended to assess 20 DSM-5 symptoms of Posttraumatic Stress Disorder. The standard recall period for the PCL-5 is one month. For CENTER-TBI a recall period of one week was used at the 2-3 week assessment, and the standard one month recall period was used at other time points. The sum of scores can range from 0 to 80, where high scores indicate more pronounced PTSD symptoms.

Outcome measures

Measure	CENTER-TBI Population n=2173 Participants Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study.	ER Stratum n=456 Participants patients admitted to the ER	Admission Stratum n=818 Participants patients admitted but not to the ICU	ICU Stratum n=899 Participants patients admitted to the ICU
6 Month Post-traumatic Stress Disorder (PTSD) Checklist for DSM-5 (PCL-5) <33 (Impaired)	201 Participants	40 Participants	77 Participants	84 Participants

SECONDARY outcome

Timeframe: 6 months

The Rivermead PCS Questionnaire (RPQ) was originally developed as a measure of severity of symptoms following MTBI. It consists of 16 post-concussion symptoms including headaches, dizziness, nausea/vomiting, noise sensitivity, sleep disturbance, fatigue, irritability, feeling depressed/tearful, feeling frustrated/ impatient, forgetfulness, poor concentration, taking longer to think, blurred vision, light sensitivity, double vision and restlessness. In the original version of the RPQ, participants are asked to rate the degree (on a scale of 0 to 4) to which a particular symptom has been absent or a mild, moderate or severe problem over the previous 7 days compared with premorbid levels. Total scores range from 0 to 64 with higher scores indicating more severe symptoms. Scores equal to or greater than 16 were considered indicative of persisting post-concussion symptoms.

Outcome measures

Measure	CENTER-TBI Population n=2259 Participants Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study.	ER Stratum n=467 Participants patients admitted to the ER	Admission Stratum n=852 Participants patients admitted but not to the ICU	ICU Stratum n=940 Participants patients admitted to the ICU
6 Month Rivermead Post Concussion Questionnaire <16 (Impaired)	643 Participants	98 Participants	200 Participants	345 Participants

SECONDARY outcome

Timeframe: 6 months

The GOAT is a standardised assessment used to determine whether a participant is in post-traumatic amnesia (PTA). PTA is an early phase of TBI recovery during which the person with injury shows markedly impaired memory, confusion, fluctuation in performance, disorientation, and other neurobehavioral signs and symptoms. GOAT questions assess orientation, memory for the first event that the participant can recall after the injury, and memory for the last event that the participant can recall from before the injury.

The GOAT's total score must be achieved by subtracting from 100 the total amount of error scores (Total score = 100 - total amount of error scores). Scores lower than 75 point to the fact that the victim is still experiencing amnesia.

Outcome measures

Measure	CENTER-TBI Population n=1607 Participants Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study.	ER Stratum n=281 Participants patients admitted to the ER	Admission Stratum n=610 Participants patients admitted but not to the ICU	ICU Stratum n=716 Participants patients admitted to the ICU
6 Month Galveston Orientation and Amnesia Test (GOAT) < 75 (Impaired)	67 Participants	6 Participants	8 Participants	53 Participants

SECONDARY outcome

Timeframe: 6 months

The Rey Auditory Verbal Learning Test (RAVLT) is a test of verbal memory that assesses the ability to acquire 15 words. Recall is assessed after each presentation of the list, after the recall of an interference list, and again following a 20-minute delay. The total score for recall of the principal list ranges from 0 to 75, with higher scores indicating better performance.

Impairment was defined as performance that was 1.33 SDs below the mean of a reference group of healthy peers.

Outcome measures

Measure	CENTER-TBI Population n=1823 Participants Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study.	ER Stratum n=368 Participants patients admitted to the ER	Admission Stratum n=705 Participants patients admitted but not to the ICU	ICU Stratum n=750 Participants patients admitted to the ICU
6 Month Rey Auditory Verbal Learning Test (RAVLT) - Impaired	350 Participants	45 Participants	107 Participants	198 Participants

SECONDARY outcome

Timeframe: 6 months

In the timed up and go (TUG) test, subjects are asked to rise from a standard armchair, walk to a marker 3 m away, turn, walk back, and sit down again, for quantifying functional mobility. The presence of slowness, hesitancy, abnormal trunk or arm movements, staggering or stumbling is used to grade the patient from 1 (normal) to 5 (severely abnormal). Impaired mobility was defined as taking 14 seconds or longer to perform the TUG test.

Outcome measures

Measure	CENTER-TBI Population n=1481 Participants Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study.	ER Stratum n=293 Participants patients admitted to the ER	Admission Stratum n=554 Participants patients admitted but not to the ICU	ICU Stratum n=634 Participants patients admitted to the ICU
6 Month Timed up and go Test - Impaired	342 Participants	62 Participants	108 Participants	172 Participants

SECONDARY outcome

Timeframe: 6 months

The Coma Recovery Scale- Revised (CRS-R) is a standardized behavioral assessment instrument designed to measure neurobehavioral function in patients with disorders of consciousness (DOC). The CRS-R is comprised of six subscales addressing auditory, visual, motor, oromotor/verbal, communication and arousal functions. Subscale items are hierarchically-arranged, corresponding to brain stem, subcortical and cortically-mediated functions. Scores range between 0 (deep coma) and 23 (able to follow commands and to use objects purposefully). A total score less than 23 indicates impairment.

Outcome measures

Measure	CENTER-TBI Population n=227 Participants Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study.	ER Stratum n=92 Participants patients admitted to the ER	Admission Stratum n=135 Participants patients admitted but not to the ICU	ICU Stratum patients admitted to the ICU
6 Month JK Coma Recovery Scale - Revised <23 (Impaired)	17 Participants	0 Participants	17 Participants	—

SECONDARY outcome

Timeframe: 6 months

The Trail Making Test (TMT) is a measure of attention, speed, and mental flexibility. Part A requires the individual to draw lines to connect 25 encircled numbers distributed on a page. Part B is similar except the person must alternate between numbers and letters and is more difficult and takes longer to complete. Both sections are timed and the score represents the amount of time required to complete the task, with shorter times indicating better performance. The maximum time allowed is 100 seconds.

Impairment cutoff: > 55.9 (based on the comparison group as a whole and expressed as raw score).

For all the cognitive tests impairment was defined as performance that was 1.33 SDs below the mean of a reference group of healthy peers. Raw scores indicating impaired performance could be > or < than the mean depending on the test (eg. on tests of accuracy the cut-off will be a score 1.33 SDs below the mean, while on a timed test the cut-off will be 1.33 SDs above the mean).

Outcome measures

Measure	CENTER-TBI Population n=1853 Participants Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study.	ER Stratum n=373 Participants patients admitted to the ER	Admission Stratum n=720 Participants patients admitted but not to the ICU	ICU Stratum n=760 Participants patients admitted to the ICU
6 Month Trail Making Test (TMT) Part A - Impaired	402 Participants	46 Participants	134 Participants	222 Participants

SECONDARY outcome

Timeframe: 6 months

The TMT is a measure of attention, speed, and mental flexibility. Part A requires the individual to draw lines to connect 25 encircled numbers distributed on a page. Part B is similar except the person must alternate between numbers and letters, is more difficult, takes longer to complete. Both sections are timed, the score represents the amount of time required to complete the task, with shorter times indicating better performance.

Impairment cutoff: > 143.7 (based on the comparison group as a whole and expressed as raw score).

For all the cognitive tests impairment was defined as performance that was 1.33 SDs below the mean of a reference group of healthy peers. Raw scores indicating impaired performance could be > or < than the mean depending on the test (eg. on tests of accuracy the cut-off will be a score 1.33 SDs below the mean, while on a timed test the cut-off will be 1.33 SDs above the mean).

Outcome measures

Measure	CENTER-TBI Population n=1799 Participants Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study.	ER Stratum n=365 Participants patients admitted to the ER	Admission Stratum n=702 Participants patients admitted but not to the ICU	ICU Stratum n=732 Participants patients admitted to the ICU
6 Month Trail Making Test (TMT) Part B - Impaired	368 Participants	46 Participants	113 Participants	209 Participants

SECONDARY outcome

Timeframe: 6 months

CANTAB is a computerized neuropsychological battery examining a range of domains including attention, memory and executive functioning. Using mainly nonverbal stimuli, the test is language- and culture-independent. For CANTAB PAL, the individual must remember 1 to 8 patterns displayed in different positions on the screen. The score is the number of incorrect responses adjusted if necessary for trials that have not been completed. Scores ranged from 0-194 with lower score indicating better performance.

Impairment cutoff: > 72.3 (based on the comparison group as a whole and expressed as raw score).

For all the cognitive tests impairment was defined as performance that was 1.33 SDs below the mean of a reference group of healthy peers. Raw scores indicating impaired performance could be > or < than the mean depending on the test (eg. on tests of accuracy the cut-off will be a score 1.33 SDs below the mean, while on a timed test the cut-off will be 1.33 SDs above the mean).

Outcome measures

Measure	CENTER-TBI Population n=1546 Participants Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study.	ER Stratum n=342 Participants patients admitted to the ER	Admission Stratum n=587 Participants patients admitted but not to the ICU	ICU Stratum n=617 Participants patients admitted to the ICU
6 Month Cambridge Neuropsychological Test Automated Battery (CANTAB) PAL (Paired Associate Learning Task) - Impaired	231 Participants	42 Participants	72 Participants	117 Participants

SECONDARY outcome

Timeframe: 6 months

The CANTAB is a computerized neuropsychological battery examining a range of domains including attention, memory and executive functioning. Using mainly nonverbal stimuli, the test is language- and culture-independent. For CANTAB RTI, the individual must respond as quickly as possible to a circle presented at one of 5 positions. The outcome measure is the median time for correct responses (ms).

Impairment cutoff: > 470.9 (based on the comparison group as a whole and expressed as raw score).

For all the cognitive tests impairment was defined as performance that was 1.33 SDs below the mean of a reference group of healthy peers. Raw scores indicating impaired performance could be > or < than the mean depending on the test (eg. on tests of accuracy the cut-off will be a score 1.33 SDs below the mean, while on a timed test the cut-off will be 1.33 SDs above the mean).

Outcome measures

Measure	CENTER-TBI Population n=1462 Participants Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study.	ER Stratum n=321 Participants patients admitted to the ER	Admission Stratum n=542 Participants patients admitted but not to the ICU	ICU Stratum n=599 Participants patients admitted to the ICU
6 Month Cambridge Neuropsychological Test Automated Battery (CANTAB) RTI (Reaction Time Task) - Impaired	237 Participants	38 Participants	63 Participants	136 Participants

SECONDARY outcome

Timeframe: 6 months

The CANTAB is a computerized neuropsychological battery examining a range of domains including attention, memory and executive functioning. Using mainly nonverbal stimuli, the test is language- and culture-independent. For the CANTAB SWM, the participant searches for tokens in boxes on the screen. The between errors measure is the number of times the participant queries a box that has already been searched. Errors ranged from 0 to 151, with lower numbers indicating better performance.

Impairment cutoff: > 52.0 (based on the comparison group as a whole and expressed as raw score).

For all the cognitive tests impairment was defined as performance that was 1.33 SDs below the mean of a reference group of healthy peers. Raw scores indicating impaired performance could be > or < than the mean depending on the test (eg. on tests of accuracy the cut-off will be a score 1.33 SDs below the mean, while on a timed test the cut-off will be 1.33 SDs above the mean).

Outcome measures

Measure	CENTER-TBI Population n=1483 Participants Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study.	ER Stratum n=334 Participants patients admitted to the ER	Admission Stratum n=564 Participants patients admitted but not to the ICU	ICU Stratum n=585 Participants patients admitted to the ICU
6 Month Cambridge Neuropsychological Test Automated Battery (CANTAB) SWM (Spatial Working Memory Task) - Impaired	259 Participants	49 Participants	81 Participants	129 Participants

SECONDARY outcome

Timeframe: 6 months

The CANTAB is a computerized neuropsychological battery examining a range of domains including attention, memory and executive functioning. Using mainly nonverbal stimuli, the test is language- and culture-independent. For the CANTAB RVP, sequences of numbers must be detected as they appear on the screen. The measure of accuracy is A' (A prime) which is derived from hits and correct rejections. The maximum score is 1 and, a higher A' indicates better performance.

Impairment cutoff: < 0.82 (based on the comparison group as a whole and expressed as raw score).

For all the cognitive tests impairment was defined as performance that was 1.33 SDs below the mean of a reference group of healthy peers. Raw scores indicating impaired performance could be > or < than the mean depending on the test (eg. on tests of accuracy the cut-off will be a score 1.33 SDs below the mean, while on a timed test the cut-off will be 1.33 SDs above the mean).

Outcome measures

Measure	CENTER-TBI Population n=1368 Participants Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study.	ER Stratum n=311 Participants patients admitted to the ER	Admission Stratum n=514 Participants patients admitted but not to the ICU	ICU Stratum n=543 Participants patients admitted to the ICU
6 Month Cambridge Neuropsychological Test Automated Battery (CANTAB) RVP (Rapid Visual Information Processing Task) - Impaired	225 Participants	33 Participants	46 Participants	146 Participants

SECONDARY outcome

Timeframe: 6 months

The CANTAB is a computerized neuropsychological battery examining a range of domains including attention, memory and executive functioning. Using mainly nonverbal stimuli, the test is language- and culture-independent. For the CANTAB SOC, the individual moves circles to match a target in this task based on the Tower of Hanoi game. The score is the number of problems solved in the minimum number of moves, with a maximum of 12. Higher scores indicate better performance.

Impairment cutoff: < 5.7(based on the comparison group as a whole and expressed as raw score).

For all the cognitive tests impairment was defined as performance that was 1.33 SDs below the mean of a reference group of healthy peers. Raw scores indicating impaired performance could be > or < than the mean depending on the test (eg. on tests of accuracy the cut-off will be a score 1.33 SDs below the mean, while on a timed test the cut-off will be 1.33 SDs above the mean).

Outcome measures

Measure	CENTER-TBI Population n=1440 Participants Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study.	ER Stratum n=329 Participants patients admitted to the ER	Admission Stratum n=548 Participants patients admitted but not to the ICU	ICU Stratum n=563 Participants patients admitted to the ICU
6 Month Cambridge Neuropsychological Test Automated Battery (CANTAB) SOC (Stockings of Cambridge Task) - Impaired	182 Participants	28 Participants	64 Participants	90 Participants

SECONDARY outcome

Timeframe: 6 months

The CANTAB is a computerized neuropsychological battery examining a range of domains including attention, memory and executive functioning. Using mainly nonverbal stimuli, the test is language- and culture-independent. For the CANTAB AST, participants respond either to the position of an arrow or the direction it is pointing, after being cued to the task on each trial. Total correct responses range from 0 to 160, where higher numbers indicate better performance.

Impairment cutoff: <135.5 (based on the comparison group as a whole and expressed as raw score).

For all the cognitive tests impairment was defined as performance that was 1.33 SDs below the mean of a reference group of healthy peers. Raw scores indicating impaired performance could be > or < than the mean depending on the test (eg. on tests of accuracy the cut-off will be a score 1.33 SDs below the mean, while on a timed test the cut-off will be 1.33 SDs above the mean).

Outcome measures

Measure	CENTER-TBI Population n=1488 Participants Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study.	ER Stratum n=332 Participants patients admitted to the ER	Admission Stratum n=559 Participants patients admitted but not to the ICU	ICU Stratum n=597 Participants patients admitted to the ICU
6 Month Cambridge Neuropsychological Test Automated Battery (CANTAB) AST (Attention Switching Task ) - Impaired	282 Participants	49 Participants	85 Participants	148 Participants

SECONDARY outcome

Timeframe: Between 2-3 weeks after enrolment

A selected number of sites performed MRI follow up in a subset of patients that consented for imaging data collection. The CENTER-TBI MR protocols included a high-resolution 3D T1-weighted, a T2-weighted, a FLAIR, a DTI, a T2* sequence (gradient echo and/or SWI), and (optionally) a resting-state fMRI. Across all stratum the MRI sites performed a follow up MRI at 2-3 weeks after injury.

Traumatic Intracranial Abnormalities were assessed according to the TBI-Common Data Elements (CDEs). It indicates whether any of the 12 following imaging abnormalities are present (Mass lesion, Extra-axial Hematoma, Epidural Hematoma, Subdural Hematoma Acute, Subdural Hematoma Subacute Chronic, Subdural Collection Mixed Density, Contusion, TAI, traumatic Subarachnoid Hemorrhage, Intraventricular Hemorrhage, Midline Shift or Cisternal Compression.

Outcome measures

Measure	CENTER-TBI Population n=504 Participants Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study.	ER Stratum n=123 Participants patients admitted to the ER	Admission Stratum n=180 Participants patients admitted but not to the ICU	ICU Stratum n=197 Participants patients admitted to the ICU
Early (2-3 Weeks) MRI Imaging - Traumatic Intracranial Abnormalities	312 Participants	32 Participants	101 Participants	179 Participants

Adverse Events

CENTER-TBI Population

Serious events: 0 serious events

Other events: 0 other events

Deaths: 363 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Prof. Em. Dr Andrew Maas

UZA

Phone: 0032 3 821 45 37

Email: andrew.maas@uza.be

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60