Clinical trial NCT05413499: Blood Biomarkers to Improve Management of Children With Traumatic Brain Injury
Official title: BRAINI2-Paediatric : Blood Biomarkers to Improve Management of Children With Traumatic Brain Injury: a European, Prospective, Multicentre Clinical Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Traumatic Brain Injury
Keywords: TBI / Biomarkers / paediatric
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2022-06-10
Enrollment: 2880
Sex: ALL
Minimum age (years): 0
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: Mild traumatic brain injury (TBI), defined by a Glasgow Coma Scale (GCS) score of 13 to 15, is the cause of many consultations in paediatric emergency departments (1), even though it is a rare cause of acute complication: approximately 10% of children present with intracranial lesions (ICL) on the CT scan and less than 1% require neurosurgical intervention (2). Although ICLs remain a serious complication requiring rapid diagnosis, brain CT scans, the gold standard diagnostic test, cannot be performed routinely because many children would be unnecessarily exposed to ionising radiation associated with an increased risk of cancer (3). In recent years, several clinical decision rules for the management of mTBI have therefore been developed with the aim of identifying children at high or very low risk of ICL in order to better target CT scan indications. Despite this, the rate of CT scans performed has remained high, up to 35%, and has not decreased with the application of these clinical decision rules (4).

Furthermore, even though the majority of children and adolescents recover quickly after mTBI, nearly 30% will present symptoms such as headaches, dizziness, asthenia, memory, concentration or sleep disorders persisting beyond one month with a possible impact on their quality of life (5). Thus, there is a need to develop new strategies to (i) limit the use of CT scans while minimising the risk of late diagnosis of ICL, (ii) identify children with a higher risk of adverse outcome and/or post-concussive symptoms.

One of the most promising strategies is the use of brain-based blood biomarkers. This study therefore aims to provide new knowledge on two of them, GFAP and UCH-L1 (6,7), in particular by using an automated test combining them (the VIDAS® TBI test developed by bioMérieux) in order to improve the management of CT in the paediatric population at the diagnostic and prognostic levels.


Eligibility criteria: Inclusion Criteria:

Children and adolescents \<18 years old Consent from one of the parents of the child or from holder of parental responsibility Consent from the child or adolescent Parental affiliation with an appropriate health insurance system

1. TBI population

   * Admission within 24 hours of the injury
   * Ability to follow-up by telephone, mail or email
   * For the mTBI group:

     * GCS score of 13-15 on admission
     * Indication for cerebral CT scan according to national or local guidelines or the in-charge physician OR diagnosis of concussion consistent with the fourth Zurich consensus statement (9) . Concussion was defined as a complex pathophysiological process caused by a direct blow to the head, face, neck, or elsewhere on the body with an impulsive force transmitted to the head (which may or may not have involved loss of consciousness), resulting in a brain injury with one or more symptoms in one or more of the following clinical domains: somatic, cognitive, emotional or behavioural, or sleep. To objectively help diagnose concussion, the validated Acute Concussion Evaluation (ACE) questionnaire (10) for children with mTBI will be used, the presence of ≥ 1 symptom on the ACE defines concussion.
   * For the moderate or severe TBI group:

     * GCS score of 3-12 on admission
     * Indication for cerebral CT scan according to national or local guidelines or the in-charge physician
2. Non-TBI control paediatric population

   * Admission for any reason other than TBI
   * Indication of blood sampling for their routine management
   * GCS score of 15
   * Otherwise healthy, i.e. without chronic pathology

Exclusion Criteria:

1. TBI population

   * Time of injury unknown or exceeding 24 hours
   * Blood sampling not possible within 24 hours after the injury or 6 hours after the CT scan, if applicable
   * Penetrating brain injury with skull fracture
   * Pre-existing neurological disorders affecting the assessment of neurological outcome, seizure disorder/epilepsy, brain tumour, history of neurosurgery, stroke, encephalopathy
   * Venepuncture not feasible
   * Pregnant woman
   * Intoxication
   * No clear primary mechanism of trauma
   * No possibility for transferring CT scan images to the centralised platform in case of neuroimaging only performed in an outside hospital before transfer
   * Participation in another interventional research study
2. Non-TBI control paediatric population

   * Pre-existing neurological disorders, seizure disorder/epilepsy, brain tumour, history or indication of neurosurgery, stroke, encephalopathy
   * History of TBI
   * Orthopaedic trauma or surgery within the last month
   * Suspected meningitidis or encephalitis
   * Venepuncture not feasible
   * Pregnant woman
   * Intoxication
   * Participation in another interventional research study

Primary outcomes:
measure: 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 ICL on CT scan
timeFrame: Day 0
Secondary outcomes:
measure: Prediction of early and mid-term prognosis after TBI : Number of participants with Early clinical worsening
timeFrame: 72 hours after TBI
measure: Prediction of early and mid-term prognosis after TBI : Glasgow Outcome Scale-Extended, paediatric version (GOS-E Peds)
timeFrame: Month 1, Month 3
measure: Prediction of early and mid-term prognosis after TBI : ost-concussion symptoms: Rivermead Post-Concussion Symptoms Questionnaire (RPQ)
timeFrame: Month 1, Month 3
measure: Prediction of early and mid-term prognosis after TBI : Health related quality of life: PedsQL questionnaire
timeFrame: Month 1, Month 3
measure: Prediction of early and mid-term prognosis after TBI : Serum GFAP and UCH-L1 concentrations
timeFrame: Day 0
measure: Establishment of age-appropriate physiological reference values
timeFrame: Day 0
Other outcomes:
Locations:
city: Brest
country: France
facility: Brest University Hospital
city: Clermont-Ferrand
country: France
facility: Clermont-Ferrand University Hospital
city: Colombes
country: France
facility: Louis Mourier Hospital (AP-HP)
city: Grenoble
country: France
facility: Grenoble University Hospital
city: La Roche-sur-Yon
country: France
facility: La Roche/Yon Hospital
city: Lille
country: France
facility: Lille University Hospital
city: Limoges
country: France
facility: Limoges University Hospital
city: Lorient
country: France
facility: Lorient Hospital
city: Montpellier
country: France
facility: Montpellier University Hospital
city: Nantes
country: France
facility: Nantes University Hospital
city: Paris
country: France
facility: Armand Trousseau hospital (AP-HP)
city: Paris
country: France
facility: Robert Debré Hospital (AP-HP)
city: Rennes
country: France
facility: Rennes University Hospital
city: Saint-Nazaire
country: France
facility: Saint Nazaire Hospital
city: Saint-Étienne
country: France
facility: Saint Etienne University Hospital
city: Munich
country: Germany
facility: Klinikum rechts der Isar, Technical University of Munich
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron (ICS)
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Nino Jesus
city: Lucerne
country: Switzerland
facility: Luzerner Kantonsspital
Study officials:
affiliation: Nantes University Hospital
name: Fleur LORTON
role: PRINCIPAL_INVESTIGATOR
References: