BRAINI-2 Elderly Mild TBI European Study

Study Overview
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Brief Summary
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Mild traumatic brain injury (mTBI) is one of the most frequent emergencies in the elderly population. Despite most mTBI are managed with cranial computed tomography (CT), only 10% of CTs show lesions, determining CT overuse. The use of serum glial fibrillary acidic protein (GFAP) and Ubiquitin C-terminal Hydrolase-L1 (UCH-L1) have shown potential for ruling out the need for cranial CT. However evidence on biomarker use in mild TBI were not based on studies that included aged participants and patients with comorbidities for which biomarker levels could vary. This is why there is a need for a prospective study that assesses the predictive performance of these two biomarkers in the elderly population, both in elderly patients suffering mild TBI and in a reference population, including patients and participants with and without comorbidities.

Official Title
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Blood Biomarkers to Improve Management of Mild Traumatic BRAIN Injury in the Elderly

Conditions
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Mild Traumatic Brain Injury

Intervention / Treatment
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* Diagnostic Test: GFAP and UCH-L1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BRAINI2-ELDERLY DIAGNOSTIC & PROGNOSTIC: Patients ≥65 years of age Mild TBI (GCS 13-15 on admission) with indication of brain CT scan in the 12 hours after injury ; Blood sample obtained ≤12 h after injury and CT scan preferably ≤6h from blood sample. BRAINI2-ELDERLY REFERENCE: Non TBI patients ≥65 years of age Exclusion Criteria: BRAINI2-ELDERLY DIAGNOSTIC & PROGNOSTIC: Age below 65 years. GCS 3-12 on admission Time of injury unknown Time to injury exceeding 12 hours Primary admission for non-traumatic neurological disorder (e.g., stroke, spontaneous, intracranial hematoma) Penetrating head trauma Patient with mechanical ventilation from the trauma scene or prehospital management. Venipuncture not feasible No realization of brain CT-scan Subject under judiciary control Subject in inclusion period of a drug interventional study BRAINI2-ELDERLY REFERENCE: Subject in inclusion period of another drug interventional study Patients harboring a brain tumor Patients that have had a stroke or neurosurgical operation 1 month prior to the inclusion in the study.

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| BRAINI2-ELDERLY DIAGNOSTIC & PROGNOSTIC<br>2370 patients suffering mild Traumatic brain injury | Diagnostic Test: GFAP and UCH-L1<br>* 2x5mL blood samples will be used to determine the performance of the automated VIDAS TBI platform in assessing serum concentrations of GFAP and UCH-L1 to rule out the need for a CT-scan after mTBI.<br>|
| BRAINI2-ELDERLY REFERENCE<br>480 non-tbi elderly reference patients | Diagnostic Test: GFAP and UCH-L1<br>* 2x5mL blood samples will be used to determine the performance of the automated VIDAS TBI platform in assessing serum concentrations of GFAP and UCH-L1 to rule out the need for a CT-scan after mTBI.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarkers diagnostic performance | Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of GFAP and UCHL-1 used separately and in combination to detect the presence or absence of intracranial lesions on CT scan | 12 hours after mild TBI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of the potential of the two biomarkers in predicting neurological symptoms after TBI | Early and midterm biomarker predictive performance in terms of predicting neurological outcome. Neurological status at 1 week and 3 months after TBI and Rivermead post concussion questionnaire. | 1 week and 3 months | 
| GFAP reference values | GFAP serum level distribution in the non-TBI reference population, considering age and comorbidities. | 1 Day, day of extraction of the sample | 
| UCHL-1 reference values | UCHL-1 serum level distribution in the non-TBI reference population, considering age and comorbidities. | 1 Day, day of extraction of the sample | 
| Determination of the potential of the two biomarkers in predicting neurological outcome assessed by the Extended Glasgow Outcome Score (GOSE) after TBI | Early and midterm biomarker predictive performance in terms of predicting neurological outcome. Extended Glasgow Outcome Score (GOSE) | 1 week and 3 months | 
| Determination of the potential of the two biomarkers in predicting quality of life assessed by Qolibri-OS after TBI | Early and midterm biomarker predictive performance in terms of predicting quality of life after mild TBI assessed by Qolibri-OS | 1 week and 3 months | 
| Determination of the potential of the two biomarkers in predicting quality of life assessed by EQ-5D-5L after TBI | Midterm biomarker predictive performance in terms of predicting quality of life after mild TBI assessed by EQ-5D-5L | 3 months | 
| Determination of the potential of the two biomarkers in depression symptoms assessed by PHQ-9 after TBI | Midterm biomarker predictive performance in terms of predicting depression symptoms after mild TBI assessed by PHQ-9 | 3 months |