Blood Biomarkers to Improve Management of Children With Traumatic Brain Injury

NCT05413499 | Unknown

• 1 other identifier: RC21_0595
• Study Type: interventional
• Target: 2,880
• Locations: 4 countries
• Sites: 20

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.

Conditions

Traumatic Brain Injury

Keywords

TBI / Biomarkers / paediatric

Outcome Measures

Primary Outcomes (1)

• 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

  Day 0

Secondary Outcomes (6)

• Prediction of early and mid-term prognosis after TBI : Number of participants with Early clinical worsening

  72 hours after TBI

• Prediction of early and mid-term prognosis after TBI : Glasgow Outcome Scale-Extended, paediatric version (GOS-E Peds)

  Month 1, Month 3

• Prediction of early and mid-term prognosis after TBI : ost-concussion symptoms: Rivermead Post-Concussion Symptoms Questionnaire (RPQ)

  Month 1, Month 3

• Prediction of early and mid-term prognosis after TBI : Health related quality of life: PedsQL questionnaire

  Month 1, Month 3

• Prediction of early and mid-term prognosis after TBI : Serum GFAP and UCH-L1 concentrations

  Day 0

Interventions

Biomarkers research OTHER

For a part of the included population, the children with a mTBI and without indication of CT scan, a non-routine blood sample will be planned

Eligibility Criteria

• Age: 0 Days - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (20)

Brest University Hospital

Brest, France

NOT YET RECRUITING

Clermont-Ferrand University Hospital

Clermont-Ferrand, France

NOT YET RECRUITING

Louis Mourier Hospital (AP-HP)

Colombes, France

NOT YET RECRUITING

Grenoble University Hospital

Grenoble, France

NOT YET RECRUITING

La Roche/Yon Hospital

La Roche-sur-Yon, France

NOT YET RECRUITING

Lille University Hospital

Lille, France

NOT YET RECRUITING

Limoges University Hospital

Limoges, France

NOT YET RECRUITING

Lorient Hospital

Lorient, France

NOT YET RECRUITING

Montpellier University Hospital

Montpellier, France

NOT YET RECRUITING

Nantes University Hospital

Nantes, France

RECRUITING

Armand Trousseau hospital (AP-HP)

Paris, France

NOT YET RECRUITING

Robert Debré Hospital (AP-HP)

Paris, France

NOT YET RECRUITING

Rennes University Hospital

Rennes, France

NOT YET RECRUITING

Saint Etienne University Hospital

Saint-Etienne, France

NOT YET RECRUITING

Saint Nazaire Hospital

Saint-Nazaire, France

NOT YET RECRUITING

Klinikum rechts der Isar, Technical University of Munich

Munich, Germany

NOT YET RECRUITING

Hospital Universitari Vall d'Hebron (ICS)

Barcelona, Spain

NOT YET RECRUITING

Hospital 12 de Octubre

Madrid, Spain

NOT YET RECRUITING

Hospital Infantil Universitario Nino Jesus

Madrid, Spain

NOT YET RECRUITING

Luzerner Kantonsspital

Lucerne, Switzerland

NOT YET RECRUITING

Related Publications (1)

• Lorton F, Lagares A, de la Cruz J, Mejan O, Pavlov V, Sapin V, Poca MA, Lehner M, Biberthaler P, Chauvire-Drouard A, Gras-Le-Guen C, Scherdel P; BRAINI-2 paediatric Collaborative group; Collaborators. Performance of glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) biomarkers in predicting CT scan results and neurological outcomes in children with traumatic brain injury (BRAINI-2 paediatric study): protocol of a European prospective multicentre study. BMJ Open. 2024 May 15;14(5):e083531. doi: 10.1136/bmjopen-2023-083531.

  PMID: 38754888 DERIVED

MeSH Terms

Conditions

Brain Injuries, Traumatic

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Fleur LORTON

  Nantes University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fleur LORTON

CONTACT

33 (0)2 40 08 33 33; fleur.lorton@chu-nantes.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2022
• First Posted: June 10, 2022
• Study Start: August 2, 2022
• Primary Completion: January 1, 2025
• Study Completion: April 1, 2025
• Last Updated: August 24, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (15); CH (1); ES (3); DE (1)