Blood Biomarkers to Improve Management of Children With Traumatic Brain Injury

Traumatic Brain Injury Clinical Trial

— BRAINI2  

Official title:

BRAINI2-Paediatric : Blood Biomarkers to Improve Management of Children With Traumatic Brain Injury: a European, Prospective, Multicentre Clinical Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05413499
• Other study ID #: RC21_0595
• Status: Recruiting
• Phase: N/A
• Start date: August 2, 2022
• Est. completion date: April 1, 2025

Study information

• Verified date: August 2022
• Source: Nantes University Hospital
• Contact: Fleur LORTON
• Phone: 33 (0)2 40 08 33 33
• Email: fleur.lorton[@]chu-nantes.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2880
• Est. completion date: April 1, 2025
• Est. primary completion date: January 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Days to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Traumatic Brain Injury
• Wounds and Injuries

Intervention

Other:
• Biomarkers research
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

Locations

Country	Name	City	State
France	Brest University Hospital	Brest
France	Clermont-Ferrand University Hospital	Clermont-Ferrand
France	Louis Mourier Hospital (AP-HP)	Colombes
France	Grenoble University Hospital	Grenoble
France	La Roche/Yon Hospital	La Roche-sur-Yon
France	Lille University Hospital	Lille
France	Limoges University Hospital	Limoges
France	Lorient Hospital	Lorient
France	Montpellier University Hospital	Montpellier
France	Nantes University Hospital	Nantes
France	Armand Trousseau hospital (AP-HP)	Paris
France	Robert Debré Hospital (AP-HP)	Paris
France	Rennes University Hospital	Rennes
France	Saint Etienne University Hospital	Saint-Étienne
France	Saint Nazaire Hospital	Saint-Nazaire
Germany	Klinikum rechts der Isar, Technical University of Munich	Munich
Spain	Hospital Universitari Vall d'Hebron (ICS)	Barcelona
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital Infantil Universitario Nino Jesus	Madrid
Switzerland	Luzerner Kantonsspital	Lucerne

Sponsors (1)

Lead Sponsor	Collaborator
Nantes University Hospital

Countries where clinical trial is conducted

France,  Germany,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Prediction of early and mid-term prognosis after TBI : Number of participants with Early clinical worsening	Early clinical worsening defined by the occurrence of death from TBI, neurosurgical intervention, intubation for TBI, or hospital admission of two nights or more associated with ICL on CT scan for persistent neurological symptoms such as persistent alteration in mental status, recurrent emesis due to TBI, persistent severe headache, or ongoing seizure management (8), within 72 hours after TBI.	72 hours after TBI
Secondary	Prediction of early and mid-term prognosis after TBI : Glasgow Outcome Scale-Extended, paediatric version (GOS-E Peds)	Neurological outcome: Glasgow Outcome Scale-Extended, paediatric version (GOS-E Peds)	Month 1, Month 3
Secondary	Prediction of early and mid-term prognosis after TBI : ost-concussion symptoms: Rivermead Post-Concussion Symptoms Questionnaire (RPQ)	Post-concussion symptoms: Rivermead Post-Concussion Symptoms Questionnaire (RPQ)	Month 1, Month 3
Secondary	Prediction of early and mid-term prognosis after TBI : Health related quality of life: PedsQL questionnaire	Health related quality of life: PedsQL questionnaires	Month 1, Month 3
Secondary	Prediction of early and mid-term prognosis after TBI : Serum GFAP and UCH-L1 concentrations	Comparison of serum GFAP and UCH-L1 concentrations according to the TBI severity groups, i.e. mild (GCS score of 13-15), moderate (GCS score of 9-12) or severe (GCS score of 3-8)	Day 0
Secondary	Establishment of age-appropriate physiological reference values	Measure of serum GFAP and UCH-L1 concentrations in three age groups (under 2 years old, 2-9 years old and aged 10 and over) in a non-TBI control paediatric population	Day 0