Clinical Evaluation of the i-STAT TBI Test

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the clinical performance of the i-STAT TBI test for the proposed intended use; to assist in determining the need for a CT scan in patients presenting with suspected mild traumatic brain injury who are 18 years of age or older. The secondary objective of this study is the collection of additional data and specimens from all study subjects that may support other purposes related to the understanding of TBI.

Official Title
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Clinical Evaluation of the i-STAT TBI Test

Conditions
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Traumatic Brain Injury

Intervention / Treatment
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* Other: Blood Draw Within 12 Hours of Injury
* Other: 3T MRI
* Other: In-Person Outcome Assessment at Baseline
* Other: In-Person Outcome Assessment at Follow-Up
* Other: Phone Outcome Assessment
* Other: Blood Draw After 12 Hours of Injury


Participation Criteria
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Eligibility Criteria
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Acute Blood Biomarker Branch Subject Inclusion Criteria: 18 years of age or older. Subject or Legally Authorized Representative (LAR) provided informed consent for the Acute Blood Biomarker Branch (waiver of consent may be acceptable, per IRB). Subject presented to a health care facility or emergency department with a suspected traumatic brain injury resulting from an insult to the head by an external force within 12 hours of the injury. Subject has a computed tomography (CT) scan of the head with all sequences (bone and soft tissue) ordered as part of standard of care at the enrolling facility, or are transferred to the enrolling facility with a head CT scan sent from the originating facility. As a result of this head injury, the subject has sustained a traumatically induced physiological disruption of brain function, as manifested by at least one of the following: Any period of loss of consciousness Any loss of memory for events immediately before or after the injury Any alteration of mental state at the time of the injury Focal neurological deficits that may or may not be transient Acute Blood Biomarker Branch Subject Exclusion Criteria: Previous enrollment in this study, CS-2018-0009 Current (on-going) enrollment in a therapeutic or interventional clinical trial (drug or device) Primary diagnosis at the enrolling facility of ischemic or hemorrhagic stroke Time of injury is unknown and cannot be estimated Presented with penetrating head trauma or spinal cord injury (American Spinal Injury Association [ASIA] score of C or worse) at the enrolling facility Standard of care head CT scan procedures not completed prior to Emergency Department (ED) discharge. Prisoners or patients in custody Patients on psychiatric hold Follow-up Branch Subject Inclusion Criteria: Enrollment in Acute Blood Biomarker Branch Subject or LAR provided informed consent for the Acute Blood Biomarker Branch and the Follow-up Branch Follow up Branch Subject Exclusion Criteria: 1. Conditions or circumstances that would interfere with follow-up and outcome assessment, as determined by the principal investigator or delegate. Examples include: Significant polytrauma Major debilitating baseline mental health disorders (e.g. schizophrenia or bipolar disorder) Major debilitating neurological disease (e.g. stroke, cerebrovascular accident, dementia, tumor)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Acute Blood Biomarker Branch<br>Blood draw within 12 hours of injury for i-STAT Testing then processing for storage for future use Blood draw between 12 to 24 hours of injury then processing for storage for future use In-Person Outcome Assessment | Other: Blood Draw Within 12 Hours of Injury<br>* - Specimens collected for i-STAT testing and, if applicable, for optional collection of DNA for possible future genetic testing.<br>Other: In-Person Outcome Assessment at Baseline<br>* -3 Outcome Assessments administered at Baseline.<br>Other: Blood Draw After 12 Hours of Injury<br>* - Specimens collected at 12-24 hours, 2 weeks, and 6 month following injury then processed for storage for future use.<br>|
| Acute Blood Biomarker Plus Follow-up Branch<br>Blood draw at 2 weeks and 6 months following injury then processing for storage for future use In-Person Outcome Assessment at 2 weeks, 6 weeks, and 6 months following injury Phone Outcome Assessment at 3 months following injury 3T Magnetic Resonance Imaging (MRI) at 2 weeks and 6 months following injury | Other: 3T MRI<br>* - 3T Magnetic Resonance Imaging (MRI) at 2 weeks and 6 months following injury.<br>Other: In-Person Outcome Assessment at Baseline<br>* -3 Outcome Assessments administered at Baseline.<br>Other: In-Person Outcome Assessment at Follow-Up<br>* - Full set of Outcome Assessment at 2 weeks, 6 weeks, and 6 months following injury.<br>Other: Phone Outcome Assessment<br>* - 6 Outcome Assessments administered at 3 months following injury by Phone.<br>Other: Blood Draw After 12 Hours of Injury<br>* - Specimens collected at 12-24 hours, 2 weeks, and 6 month following injury then processed for storage for future use.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| i-STAT TBI Test (elevated/not elevated) relative to standard of care Computed Tomography (CT) findings | Results of the i-STAT TBI Test (elevated/not elevated) relative to CT findings for each subject. | Within 12 Hours of Traumatic Brain Injury (TBI) | 
| Clinical sensitivity, clinical specificity, negative predictive value (NPV) and positive predictive value (PPV) of the i-STAT TBI Test | Clinical sensitivity, clinical specificity, negative predictive value (NPV), and positive predictive value (PPV) of the i-STAT TBI Test. | Within 12 hours of Traumatic Brain Injury (TBI) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3T Brain Structural and Functional Magnetic Resonance Imaging (MRI) | Sagittal 3D T1 MP-RAGE/IR-SPGR Sagittal 3D T2 GRE/SWAN/SWI Axial DTI Axial Resting State functional MRI (fMRI) Sagittal 3D T2-FLAIR CUBE/SPACE/VISTA Sagittal 3D T2-TSE | 2-Weeks and 6-Months following Traumatic Brain Injury (TBI) | 
| Blood Specimens for Analysis of Biomarkers and Genetics | To support future brain research | 12-24 Hours, 2-Weeks, and 6-Months following Traumatic Brain Injury (TBI) | 
| Baseline Outcome Assessment (Composite Measure) | Rivermead Post-Concussive Symptom Questionnaire (RPQ) Brief Symptom Inventory (BSI-18) Standardized Assessment of Concussion (SAC) | At baseline following Traumatic Brain Injury (TBI) | 
| Follow-Up Outcome Assessment (Composite Measure) | Glasgow Outcome Scale Extended Revised (R-GOSE) Functional Status Exam (FSE) Posttraumatic Stress Disorder Checklist (PCL-5) Brief Symptom Inventory (BSI-18) Rivermead Post-Concussive Symptom Questionnaire (RPQ) Trail Making Test (TMT) Wechsler Adult Intelligence Scale IV - Processing Speed Index (WAIS IV-PSI) Rey Auditory Verbal Learning Test (RAVLT) Qualify of Life After Brain Injury -Overall Scale (QOLIBRI-OS) | 2-Weeks, 6-Weeks, 3-Months, and 6-Months following Traumatic Brain Injury (TBI) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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i-STAT, Traumatic Brain Injury, Biomarkers