Critical Hyperacute Assessment Research On Neurobiomarker Kinetics in Acute Brain Injury

NCT07782216 | Recruiting

• 2 other identifiers: NNGYK/12277-2/2026NKFI-1 ADVANCED 151273
• Study Type: observational
• Target: 477
• Locations: 1 country
• Sites: 4

Brief Summary

Traumatic brain injury (TBI) and other conditions that reduce blood flow to the brain - such as cardiac arrest (CA) - are life-threatening medical emergencies. When brain cells are damaged, they release specific proteins into the bloodstream. These proteins, called neurobiomarkers, can be measured in blood samples and may help doctors assess the severity of brain injury, guide treatment, and predict patient outcomes. A major gap in current knowledge is how these neurobiomarkers behave during the very first minutes and hours after injury - the so-called "hyperacute" phase - especially when patients are still being treated by paramedics or have just arrived at the emergency department (ED). It is not yet clear whether biomarker levels rise immediately at the moment of injury or gradually over time, and how quickly they can be reliably detected. The CHARON study investigates the time-dependent kinetics of key neurobiomarkers - including S100B, glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), neurofilament light chain (NFL), and Tau proteins- during the hyperacute phase of acute brain injury. In addition to these proteins, microRNAs, polar metabolites, and lipid metabolites are also examined as potential biomarkers. The study enrolls three groups of participants:

• Patients with severe traumatic brain injury and/or polytrauma treated in the prehospital setting and admitted to the ED with T1 (highest priority) triage classification.
• Patients with CA treated (resuscitated) in the prehospital setting.
• Patients with severe traumatic brain injury enrolled at hospital (ED) admission. Serial blood samples are collected at multiple time points, beginning during prehospital care and continuing through the first 24 hours of hospital admission. No experimental treatments are given - all participants receive standard medical care. By analyzing biomarker concentration and kinetics across all three groups and correlating findings with neurological outcome at 30 days, the investigators aim to identify the most clinically effective neurobiomarkers for early diagnosis and prognosis of acute brain injury. The study is a prospective multi-center investigation conducted at emergency departments, intensive care units, and ambulance services across Hungary.

Conditions

Brain Injuries, Traumatic; Brain Injuries, Acute; Hypoxia, Brain; Cardiac Arrest (CA)

Keywords

Biomarkers; Acute-phase Proteins; Kinetics; Prehospital Emergency Care; Emergency Medicine; Brain Injuries; S100 Calcium Binding Protein beta Subunit; Glial Fibrillary Acidic Protein; Out-of-hospital Heart Arrest

Outcome Measures

Primary Outcomes (2)

• Prehospital Mortality

  Death occurring prior to emergency department arrival, assessed in prehospital-enrolled participants.

  Day 1 (Up to 24 hours from enrollment)

• In-hospital Mortality

  Death occurring during the hospital stay, assessed in all study arms.

  Up to 30 days

Secondary Outcomes (10)

• Prehospital Neurological Status

  Baseline (At first prehospital contact)

• Abbreviated Injury Scale Score Assessment

  [Time Frame: Day 1 (Up to 24 hours from enrollment)]

• Injury Severity Score Assessment

  [Time Frame: Day 1 (Up to 24 hours from enrollment)]

• Severity of Intracranial Pathology on Admission CT - Marshall Classification

  [Time Frame: Day 1 (Up to 24 hours from enrollment)]

• Severity of Intracranial Pathology on Admission CT - Rotterdam CT Score

  [Time Frame: Day 1 (Up to 24 hours from enrollment)]

Study Arms (3)

Prehospital TBI: Traumatic brain injury patients treated in prehospital setting

Serial blood samples are collected from severely injured traumatic brain injury and/or polytrauma patients (ISS \>16 and/or GCS \<9) categorized as T1 triage in the prehospital setting. Sampling occurs at two prehospital time points (immediately after intravenous access is secured; immediately before transport initiation) and at four in-hospital time points (upon emergency department admission; 1, 6, and 24 hours after ED admission). No experimental intervention is administered; participants receive standard emergency care.

Prehospital Cardiac Arrest: Cardiac arrest patients treated in the prehospital setting

Serial blood samples are collected from cardiac arrest patients managed in the prehospital setting. Sampling occurs at three prehospital time points (after the first adrenaline dose or defibrillation; at 20 minutes of ongoing resuscitation; at return of spontaneous circulation or prior to declaration of death) and at four in-hospital time points (upon emergency department admission; 1, 6, and 24 hours after ED admission). No experimental intervention is administered; participants receive standard resuscitation care.

In-hospital TBI: Severe TBI patients enrolled at hospital admission

Serial blood samples are collected from severe TBI patients (ISS \>16 and/or GCS \<9) enrolled upon emergency department admission. Sampling occurs at four time points: upon ED admission and at 1, 6, and 24 hours after admission. No experimental intervention is administered; participants receive standard emergency and intensive care.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adults aged 18 years or older presenting to emergency departments or prehospital emergency services in Hungary with acute brain injury (traumatic brain injury or cardiac arrest). Participants are enrolled consecutively at emergency departments, intensive care units, and by the Hungarian National Ambulance Service across multiple regions of Hungary.

You may qualify if:

• Age 18 years or older (all arms)
• Polytraumatized patients categorized as T1 triage by the first responder based on injury mechanism and/or sustained injuries, with intubation indicated by the first responder (Arm 1)
• Cardiac arrest treated in the prehospital setting (Arm 2)
• Severe traumatic brain injury enrolled at hospital admission (Arm 3)

You may not qualify if:

• Age under 18 years
• Pre-existing neurological or psychiatric conditions
• Hypothermia or hyperthermia at the time of enrollment
• Pregnancy

Sponsors & Collaborators

• University of Pecs: lead
• Örebro University, Sweden: collaborator

Study Sites (4)

University of Pécs Clinical Center, Department of Emergency Medicine

Pécs, Branya, 7624, Hungary

RECRUITING

Petz Aladár University Teaching Hospital, Emergency Department

Győr, Győr-Moson-Sopron, 9024, Hungary

RECRUITING

Hungarian National Ambulance Service

Budapest, Pest County, 1055, Hungary

RECRUITING

North Pest Central Hospital - Military Hospital, Emergency Centre

Budapest, Pest County, 1134, Hungary

RECRUITING

Related Publications (15)

• Gilje P, Gidlof O, Rundgren M, Cronberg T, Al-Mashat M, Olde B, Friberg H, Erlinge D. The brain-enriched microRNA miR-124 in plasma predicts neurological outcome after cardiac arrest. Crit Care. 2014 Mar 3;18(2):R40. doi: 10.1186/cc13753.

  PMID: 24588965 BACKGROUND

• Thomas I, Dickens AM, Posti JP, Czeiter E, Duberg D, Sinioja T, Krakstrom M, Retel Helmrich IRA, Wang KKW, Maas AIR, Steyerberg EW, Menon DK, Tenovuo O, Hyotylainen T, Buki A, Oresic M; CENTER-TBI Participants and Investigators. Serum metabolome associated with severity of acute traumatic brain injury. Nat Commun. 2022 May 10;13(1):2545. doi: 10.1038/s41467-022-30227-5.

  PMID: 35538079 BACKGROUND

• Moseby-Knappe M, Mattsson-Carlgren N, Stammet P, Backman S, Blennow K, Dankiewicz J, Friberg H, Hassager C, Horn J, Kjaergaard J, Lilja G, Rylander C, Ullen S, Unden J, Westhall E, Wise MP, Zetterberg H, Nielsen N, Cronberg T. Serum markers of brain injury can predict good neurological outcome after out-of-hospital cardiac arrest. Intensive Care Med. 2021 Sep;47(9):984-994. doi: 10.1007/s00134-021-06481-4. Epub 2021 Aug 21.

  PMID: 34417831 BACKGROUND

• Nolan JP, Sandroni C, Bottiger BW, Cariou A, Cronberg T, Friberg H, Genbrugge C, Haywood K, Lilja G, Moulaert VRM, Nikolaou N, Olasveengen TM, Skrifvars MB, Taccone F, Soar J. European Resuscitation Council and European Society of Intensive Care Medicine guidelines 2021: post-resuscitation care. Intensive Care Med. 2021 Apr;47(4):369-421. doi: 10.1007/s00134-021-06368-4. Epub 2021 Mar 25.

  PMID: 33765189 BACKGROUND

• Hoiland RL, Rikhraj KJK, Thiara S, Fordyce C, Kramer AH, Skrifvars MB, Wellington CL, Griesdale DE, Fergusson NA, Sekhon MS. Neurologic Prognostication After Cardiac Arrest Using Brain Biomarkers: A Systematic Review and Meta-analysis. JAMA Neurol. 2022 Apr 1;79(4):390-398. doi: 10.1001/jamaneurol.2021.5598.

  PMID: 35226054 BACKGROUND

• Hossain I, Marklund N, Czeiter E, Hutchinson P, Buki A. Blood biomarkers for traumatic brain injury: A narrative review of current evidence. Brain Spine. 2023 Dec 14;4:102735. doi: 10.1016/j.bas.2023.102735. eCollection 2024.

  PMID: 38510630 BACKGROUND

• Mondello S, Amrein K, Czeiter E, Citerio G, Diaz-Arrastia R, Gao G, Lagares A, Manley GT, Menon DK, Newcombe V, Posti JP, Wilson L, Zetterberg H, Steyerberg EW, Buki A, Maas AIR. Prognostic Value of Blood-Based Protein Biomarkers in Traumatic Brain Injury: A Living Systematic Review and Meta-Analysis. J Neurotrauma. 2025 Aug;42(15-16):1256-1286. doi: 10.1089/neu.2024.0620. Epub 2025 May 27.

  PMID: 40432557 BACKGROUND

• Czeiter E, Amrein K, Gravesteijn BY, Lecky F, Menon DK, Mondello S, Newcombe VFJ, Richter S, Steyerberg EW, Vyvere TV, Verheyden J, Xu H, Yang Z, Maas AIR, Wang KKW, Buki A; CENTER-TBI Participants and Investigators. Blood biomarkers on admission in acute traumatic brain injury: Relations to severity, CT findings and care path in the CENTER-TBI study. EBioMedicine. 2020 Jun;56:102785. doi: 10.1016/j.ebiom.2020.102785. Epub 2020 May 25.

  PMID: 32464528 BACKGROUND

• Marijon E, Narayanan K, Smith K, Barra S, Basso C, Blom MT, Crotti L, D'Avila A, Deo R, Dumas F, Dzudie A, Farrugia A, Greeley K, Hindricks G, Hua W, Ingles J, Iwami T, Junttila J, Koster RW, Le Polain De Waroux JB, Olasveengen TM, Ong MEH, Papadakis M, Sasson C, Shin SD, Tse HF, Tseng Z, Van Der Werf C, Folke F, Albert CM, Winkel BG. The Lancet Commission to reduce the global burden of sudden cardiac death: a call for multidisciplinary action. Lancet. 2023 Sep 9;402(10405):883-936. doi: 10.1016/S0140-6736(23)00875-9. Epub 2023 Aug 27.

  PMID: 37647926 BACKGROUND

• Maas AIR, Menon DK, Adelson PD, Andelic N, Bell MJ, Belli A, Bragge P, Brazinova A, Buki A, Chesnut RM, Citerio G, Coburn M, Cooper DJ, Crowder AT, Czeiter E, Czosnyka M, Diaz-Arrastia R, Dreier JP, Duhaime AC, Ercole A, van Essen TA, Feigin VL, Gao G, Giacino J, Gonzalez-Lara LE, Gruen RL, Gupta D, Hartings JA, Hill S, Jiang JY, Ketharanathan N, Kompanje EJO, Lanyon L, Laureys S, Lecky F, Levin H, Lingsma HF, Maegele M, Majdan M, Manley G, Marsteller J, Mascia L, McFadyen C, Mondello S, Newcombe V, Palotie A, Parizel PM, Peul W, Piercy J, Polinder S, Puybasset L, Rasmussen TE, Rossaint R, Smielewski P, Soderberg J, Stanworth SJ, Stein MB, von Steinbuchel N, Stewart W, Steyerberg EW, Stocchetti N, Synnot A, Te Ao B, Tenovuo O, Theadom A, Tibboel D, Videtta W, Wang KKW, Williams WH, Wilson L, Yaffe K; InTBIR Participants and Investigators. Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research. Lancet Neurol. 2017 Dec;16(12):987-1048. doi: 10.1016/S1474-4422(17)30371-X. Epub 2017 Nov 6. No abstract available.

  PMID: 29122524 BACKGROUND

• Mondello S, Sorinola A, Czeiter E, Vamos Z, Amrein K, Synnot A, Donoghue E, Sandor J, Wang KKW, Diaz-Arrastia R, Steyerberg EW, Menon DK, Maas AIR, Buki A. Blood-Based Protein Biomarkers for the Management of Traumatic Brain Injuries in Adults Presenting to Emergency Departments with Mild Brain Injury: A Living Systematic Review and Meta-Analysis. J Neurotrauma. 2021 Apr 15;38(8):1086-1106. doi: 10.1089/neu.2017.5182. Epub 2018 Jul 2.

  PMID: 29020853 BACKGROUND

• Trivedi D, Forssten MP, Cao Y, Ismail AM, Czeiter E, Amrein K, Kobeissy F, Wang KKW, DeSoucy E, Buki A, Mohseni S. Screening Performance of S100 Calcium-Binding Protein B, Glial Fibrillary Acidic Protein, and Ubiquitin C-Terminal Hydrolase L1 for Intracranial Injury Within Six Hours of Injury and Beyond. J Neurotrauma. 2024 Feb;41(3-4):349-358. doi: 10.1089/neu.2023.0322.

  PMID: 38115670 BACKGROUND

• Bazarian JJ, Biberthaler P, Welch RD, Lewis LM, Barzo P, Bogner-Flatz V, Gunnar Brolinson P, Buki A, Chen JY, Christenson RH, Hack D, Huff JS, Johar S, Jordan JD, Leidel BA, Lindner T, Ludington E, Okonkwo DO, Ornato J, Peacock WF, Schmidt K, Tyndall JA, Vossough A, Jagoda AS. Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study. Lancet Neurol. 2018 Sep;17(9):782-789. doi: 10.1016/S1474-4422(18)30231-X. Epub 2018 Jul 24.

  PMID: 30054151 BACKGROUND

• Helmrich IRAR, Czeiter E, Amrein K, Buki A, Lingsma HF, Menon DK, Mondello S, Steyerberg EW, von Steinbuchel N, Wang KKW, Wilson L, Xu H, Yang Z, van Klaveren D, Maas AIR; CENTER-TBI participants and investigators. Incremental prognostic value of acute serum biomarkers for functional outcome after traumatic brain injury (CENTER-TBI): an observational cohort study. Lancet Neurol. 2022 Sep;21(9):792-802. doi: 10.1016/S1474-4422(22)00218-6.

  PMID: 35963262 BACKGROUND

• Papp A, Horvath LL, Nagy Z, Gaal A, Debreczeni R, Pinter T, Czeiter E, Vamos Z; Experimental Oxiology Workgroup Collaborators. Post-cardiac arrest brain injury model: neurobiomarker kinetics following global cerebral hypoperfusion-reperfusion. Resuscitation. 2026 May;222:111063. doi: 10.1016/j.resuscitation.2026.111063. Epub 2026 Mar 17.

  PMID: 41856455 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Centrifuged serum and EDTA plasma samples stored in cryovials at -80°C. Samples are collected at multiple time points per participant across prehospital and in-hospital phases and retained at the Szentágothai Research Centre, University of Pécs, Hungary.

MeSH Terms

Conditions

Brain Injuries, Traumatic; Brain Injuries; Hypoxia, Brain; Heart Arrest; Out-of-Hospital Cardiac Arrest

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Heart Diseases; Cardiovascular Diseases

Central Study Contacts

Endre Czeiter, MD, PhD

CONTACT

+36205576026; endre.czeiter@gmail.com

Ábel Papp, MD

CONTACT

+36305539282; pappabel0219@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 12, 2026
• First Posted: August 24, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: September 29, 2026

Record last verified: 2026-09

Locations

HU (4)