A Study of Biomarkers of Mild Traumatic BRAIN Injury (BRAINI)

A Prospective Clinical Study of Biomarkers of Mild Traumatic BRAIN Injury

Patients with mild traumatic brain injury (mTBI) represent a burden of patients admitted to the emergency department. According to the guidelines, a cerebral CT scan is indicated after mTBI according to the specific conditions. However, variability exists regarding the respect of these CT scan indications, and less than 10% of patients will have visible brain lesions on CT scan. Recently, serum Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin C-terminal Hydrolase-L1 (UCH-L1) biomarkers have shown ability to differentiate normal and abnormal CT scan findings after mTBI. These encouraging results prompted us to launch a prospective study using automated and quick measurements of GFAP and UCH-L1 biomarkers to validate these findings.

Study Overview

• Status: Completed
• Conditions: Mild Traumatic Brain Injury
• Intervention / Treatment: Other: 2 x 5 mL blood sample

• Study Type: Observational
• Enrollment (Actual): 1501

Contacts and Locations

Study Locations

• France
  • Annecy, France
    • Centre Hospitalier Annecy Genevois
  • Bordeaux, France
    • CHU Bordeaux
  • Dijon, France
    • CHU Dijon
  • Grenoble, France
    • Chu Grenoble Alpes
  • Lyon, France
    • Hôpital Edouard Herriot - HCL
  • Lyon, France
    • Hôpital Lyon Sud HCL
  • Montpellier, France
    • CHU Montpellier
  • Nantes, France
    • CHU Nantes
  • Poitiers, France
    • CHU Poitiers
  • Toulouse, France
    • CHU Toulouse
  • Tours, France
    • CHU Tours
  • Villefranche-sur-Saône, France
    • Hopital Nord Ouest de Villefranche Sur Saone
• Spain
  • Madrid, Spain
    • Hospital Gregorio Marañón
  • Madrid, Spain
    • Hospital de La Princesa
  • Madrid, Spain
    • Hospital del Tajo
  • Madrid, Spain
    • Hospital Universitario de 12 Octubre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

1600 patients: 1300 patients in France and 300 patients in Spain

Description

Inclusion Criteria:

• Patients >18 years old (France)
• Mild TBI (GCS 13-15 on admission) within 12 hours after injury

• Indication of brain CT scan:

  • neurological focal deficit
  • anterograde amnesia
  • Glasgow coma scale score <15 after 2 hours post-TBI
  • suspicion of vault depression fracture
  • fracture of the basal skull
  • persisting nausea, vomiting or headache
  • post-TBI seizures
  • Pre-injury treatment with antithrombotic drugs
  • Loss of consciousness or amnesia with age >65 years, fall >1m or hit pedestrian
  • Other condition requiring CT scan according to the in-charge physician.

Exclusion Criteria:

• 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
• Pre-injury neurological disorder affecting the assessment of neurological outcome: dementia, Parkinson's disease, multiple sclerosis, seizure disorder, brain tumor, and history of neurosurgery, stroke or transient ischemic attack (TIA) within the last 30 days
• Venipuncture not feasible
• No realization of brain CT-scan
• Subject under judiciary control
• Pregnant or breastfeeding woman
• Subject in exclusion period of another study

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Mild TBI; Mild TBI (GCS 13-15 on admission) within 12 hours after injury	Other: 2 x 5 mL blood sample; 2 x 5 mL blood sample to determine the performance of the automated VIDAS BTI platform in assessing serum concentrations of GFAP and UCH-L1 to rule out the need for a CT-scan after mTBI.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Performance of the VIDAS-BTI assay in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and their corresponding lower limit of 95% confidence interval by comparison with brain CT scan findings.	2 x 5mL blood sample	12 hours post Traumatic Brain Injury (TBI)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination of the added value of the two biomarkers measurements to Transcranial Doppler (TCD) performed on admission to detect patients at risk of neurological worsening and patients allowed for a safe return home	TCD measures at admission	Admission
Determination of the added value of the two biomarkers measurements to Transcranial Doppler (TCD) performed on admission to detect patients at risk of neurological worsening and patients allowed for a safe return home	Neurological status at 1 week after TBI	7 days after traumatic brain injury (TBI)
Determination of the added value of the two biomarkers measurements to Transcranial Doppler (TCD) performed on admission to detect patients at risk of neurological worsening and patients allowed for a safe return home	Quality of life after brain injury (QOLIBRI) Questionnaire	7 days after traumatic brain injury (TBI)
Determination the potential of the two biomarkers in predicting neurological outcome	Extended Glasgow Outcome Scale (GOSE)	3 month after TBI
Determination of the potential of the two biomarkers in predicting neurological outcome	Quality of life after brain injury (QOLIBRI) Questionnaire)	3 month after TBI
Determination of the potential of the two biomarkers in predicting neurological outcome	EuroQuol 5 dimensions 5 level questionnaire (EQ-5D-5L)	3 month after TBI
Determination of the potential of the two biomarkers in predicting neurological outcome	Rivermead Post-concussion symptoms Questionnaire (RPQ)	3 month after TBI

Collaborators and Investigators

• Sponsor: University Hospital, Grenoble

Publications and helpful links

General Publications

• Richard M, Lagares A, Bondanese V, de la Cruz J, Mejan O, Pavlov V, Payen JF; BRAINI investigators. Study protocol for investigating the performance of an automated blood test measuring GFAP and UCH-L1 in a prospective observational cohort of patients with mild traumatic brain injury: European BRAINI study. BMJ Open. 2021 Feb 25;11(2):e043635. doi: 10.1136/bmjopen-2020-043635.

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2019
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): September 28, 2021

Study Registration Dates

• First Submitted: July 15, 2019
• First Submitted That Met QC Criteria: July 22, 2019
• First Posted (Actual): July 25, 2019

Study Record Updates

• Last Update Posted (Actual): March 2, 2022
• Last Update Submitted That Met QC Criteria: February 28, 2022
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds, Nonpenetrating; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic; Brain Concussion
• Other Study ID Numbers: 38RC19.176; 2019-A01525-52 (Other Identifier: ID RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No