Critical Hyperacute Assessment Research On Neurobiomarker Kinetics in Acute Brain Injury (CHARON)

Investigating the Significance of Protein Biomarkers During the Hyperacute Phase of Traumatic Brain Injury and Other CNS Conditions With Hypoxia/Hypoperfusion in Emergency and Prehospital Settings (CHARON)

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.

Study Overview

• Status: Recruiting
• Conditions: Brain Injuries, Traumatic; Hypoxia, Brain; Cardiac Arrest (CA); Brain Injuries, Acute

Detailed Description

Background

Traumatic brain injury (TBI) and cardiac arrest (CA) are among the leading causes of mortality and long-term disability worldwide. Together, these conditions affect an estimated 60 million people globally each year. TBI alone accounts for 27-69 million new cases annually, while out-of-hospital cardiac arrest affects approximately 275,000 individuals per year in Europe. Both conditions share a common pathobiological pathway: acute cerebral hypoxia and hypoperfusion trigger proteolysis-associated systemic cascades among others an inflammatory response in central nervous system (CNS), resulting in the release of neuronal and glial injury markers - including S100 calcium-binding protein B (S100B), neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) - into the systemic circulation.

Six blood-based protein neurobiomarkers have been extensively studied in acute brain injury: S100B and GFAP - indicators of astroglial damage; neuron-NSE and UCH-L1 - reflecting neuronal cell body injury; neurofilament light chain (NFL) - associated with axonal damage; and Tau - signaling post-injury neurodegeneration. Beyond these proteins, microRNAs (particularly miR-124), polar metabolites, and lipid metabolites (lysophosphatidylcholines, ether phosphatidylcholines, and sphingomyelins) are also under investigation as potential biomarkers of acute brain injury.

A critical and unresolved challenge is the behavior of these biomarkers during the hyperacute phase - the first minutes to hours following injury - particularly in prehospital and emergency settings. It remains unclear whether biomarker release is instantaneous at the moment of impact or gradual and continuous over time. Serial sampling studies are scarce (especially the hyperacute prehospital phase), and significant uncertainty exists regarding the influence of secondary injuries, extracranial trauma, prehospital interventions, and hemodilution on biomarker kinetics.

Sample Collection and Processing Arterial or venous blood samples are collected at study arm-specific time points detailed below. At each time point, two blood samples are collected: one serum gel tube (8 ml) and one ethylenediaminetetraacetic acid (EDTA) plasma tube (3.5 ml). Serum tubes are allowed to coagulate at ambient temperature for 45 ± 15 minutes prior to centrifugation. EDTA plasma tubes are kept on ice immediately after collection and centrifuged as soon as possible. Both tube types are centrifuged at 1,500g (4,000 rpm) for 10 minutes. Both tube types must be centrifuged within 120 minutes after sample collection.

Following centrifugation, 5 × 0.5 ml serum and 4 × 0.5 ml plasma aliquoted to labelled cryovials and stored at -80°C (temporary storage at -20°C is acceptable).

Arm 1 - Prehospital TBI/Polytrauma:

Prehospital phase:

Sample 1: immediately after intravenous access is secured Sample 2: immediately before transport initiation

In-hospital phase:

Sample 3: upon emergency department admission Sample 4: 1 hour after ED admission Sample 5: 6 hours after ED admission Sample 6: 24 hours after ED admission

Arm 2 - Prehospital Cardiac Arrest:

Prehospital phase:

Sample 1: immediately after the first adrenaline dose (asystole/pulseless electrical activity [PEA]) or first defibrillation (ventricular fibrillation [VF]/ pulseless ventricular tachycardia [pVT]) Sample 2: at 20 minutes of ongoing resuscitation Sample 3: immediately after ROSC or prior to declaration of death

In-hospital phase:

Sample 4: upon emergency department admission Sample 5: 1 hour after ED admission Sample 6: 6 hours after ED admission Sample 7: 24 hours after ED admission

Arm 3 - In-hospital TBI:

Sample 1: upon emergency department admission Sample 2: 1 hour after ED admission Sample 3: 6 hours after ED admission Sample 4: 24 hours after ED admission

Biomarker Measurements S100B and NSE: Electrochemiluminescence immunoassay (ECLIA; Elecsys S100 and Elecsys NSE assays) on the Cobas 8000 modular analyzer (Roche Diagnostics, Mannheim, Germany) at the Department of Laboratory Medicine, University of Pécs.

Brain-derived Tau (BD-Tau) and phosphorylated Tau-217 (p-Tau-217): Immunoassay on the Beckman Coulter DXi 9000 analyzer at the Department of Laboratory Medicine, University of Pécs.

GFAP and UCH-L1: VIDAS® TBI assay on the VIDAS®3 instrument (bioMérieux SA., Marcy-l'Étoile, France) at Örebro University, Sweden.

NFL, Tau, ionized calcium-binding adaptor molecule 1 (IBA-1), IL-1β, IL-6, TNF-α: Commercially available ELISA kits using the BMG LabTech CLARIOstar multimode microplate reader (BMG Labtech GmbH, Ortenberg, Germany) at the Szentágothai Research Centre, University of Pécs.

Metabolomics and lipidomics: Polar metabolites detected via Agilent 7890B GC coupled with a 7200 Q-TOF MS; lipids quantified by ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOFMS) at Örebro University, Sweden.

MicroRNA: Cell-free total RNA isolated from 500 µl serum using the miRNeasy serum/plasma kit (Qiagen, Hilden, Germany). RNA integrity confirmed by NanoDrop 2000. Reverse transcription performed using the miRCury LNA Universal RT microRNA PCR Kit (Qiagen). Droplet digital PCR (ddPCR) targeting miR-30a, miR-487b, let-7b, miR-363, and miR-126 performed at the Department of Laboratory Medicine, University of Pécs.

Cytokine and chemokine profiling: Simultaneous detection of multiple inflammatory mediators using the Human Cytokine Array (ARY022B, R&D Systems, Minneapolis, MN, USA). Chemiluminescent signals are captured at multiple exposure times for optimal detection.

Statistical Analysis

Statistical significance threshold: p < 0.05. Given the expected non-normal distribution of biomarker data, non-parametric methods are applied as primary statistical tests, including the Mann-Whitney U test and the Kruskal-Wallis test. Diagnostic and prognostic performance is evaluated using receiver operating characteristic (ROC) curve analysis with area under the curve (AUC); AUC comparisons are performed using the DeLong test. The association with mortality and neurological outcome is examined by binary logistic regression (univariable and multivariable, with pre-defined covariates).

Sample size was determined by power analysis for binary logistic regression - the most statistically demanding analysis - using a medium effect size (Cohen's d = 0.5), α = 0.05, and a power of 0.80. A Mann-Whitney equivalent correction of +10% was applied to account for non-normality of biomarker distributions. This yields a required sample size of 159 participants per arm, for a total target enrollment of 477 participants across all three arms. No single center may contribute more than 40% of the total sample to mitigate center effects. All analyses will be performed using R software (RStudio environment), with a biostatistician involved throughout.

• Study Type: Observational
• Enrollment (Estimated): 477

Contacts and Locations

• Study Contact: Name: Endre Czeiter, MD, PhD; Phone Number: +36205576026; Email: endre.czeiter@gmail.com
• Study Contact Backup: Name: Ábel Papp, MD; Phone Number: +36305539282; Email: pappabel0219@gmail.com

Study Locations

• Hungary
  • Branya
    • Pécs, Branya, Hungary, 7624
      • Recruiting
      • University of Pécs Clinical Center, Department of Emergency Medicine
      • Contact: Zoltán Vámos, MD, PhD; Phone Number: +36303573557; Email: zoltan.vamos.zoltan@gmail.com
      • Principal Investigator: Zoltán Vámos, MD, PhD
  • Győr-Moson-Sopron
    • Győr, Győr-Moson-Sopron, Hungary, 9024
      • Recruiting
      • Petz Aladár University Teaching Hospital, Emergency Department
      • Contact: Péter Cséplő, MD, PhD; Phone Number: +36702505028; Email: cseplopeti@gmail.com
      • Principal Investigator: Péter Cséplő, MD, PhD
  • Pest County
    • Budapest, Pest County, Hungary, 1055
      • Recruiting
      • Hungarian National Ambulance Service
      • Contact: Ábel Papp, MD; Phone Number: +36305539282; Email: pappabel0219@gmail.com
      • Principal Investigator: Ábel Papp, MD
    • Budapest, Pest County, Hungary, 1134
      • Recruiting
      • North Pest Central Hospital - Military Hospital, Emergency Centre
      • Contact: Levente L Horvath, MD; Phone Number: +36305533641; Email: leventehory.horvath@gmail.com
      • Principal Investigator: Levente L Horvath, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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.

Description

Inclusion Criteria

• 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)

Exclusion Criteria (all arms)

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prehospital Neurological Status	Glasgow Coma Scale (GCS) score documented by the first-responding paramedic at the scene, prior to sedation or intubation. The GCS ranges from 3 (deep unconsciousness) to 15 (fully alert); higher scores indicate better neurological status.	Baseline (At first prehospital contact)
Abbreviated Injury Scale Score Assessment	The Abbreviated Injury Scale (AIS) categorizes injuries by body region on a scale from 1 (minor) to 6 (unsurvivable); higher scores indicate greater injury severity. Calculated based on clinical and imaging parameters at emergency department admission.	[Time Frame: Day 1 (Up to 24 hours from enrollment)]
Injury Severity Score Assessment	The Injury Severity Score (ISS) is an anatomical scoring system ranging from 0 to 75; higher scores indicate greater overall injury severity. The ISS is calculated from Abbreviated Injury Scale (AIS) scores, using clinical and imaging parameters assessed upon emergency department admission.	[Time Frame: Day 1 (Up to 24 hours from enrollment)]
Severity of Intracranial Pathology on Admission CT - Marshall Classification	Categories range from I (no visible intracranial pathology) to VI (diffuse injury with mass lesion); higher categories indicate greater severity of intracranial injury.	[Time Frame: Day 1 (Up to 24 hours from enrollment)]
Severity of Intracranial Pathology on Admission CT - Rotterdam CT Score	Initial head CT scan scored according to the Rotterdam CT Score. The score ranges from 1 to 6; higher scores indicate greater severity of intracranial injury and worse predicted outcome.	[Time Frame: Day 1 (Up to 24 hours from enrollment)]
30-day Neurological Outcome in Cardiac Arrest Patients	Neurological outcome at 30 days assessed by the Cerebral Performance Scale (CPC) in cardiac arrest patients (Arm 2). The CPC ranges from 1 (good cerebral performance) to 5 (brain death); higher scores indicate worse neurological outcome.	30 days after cardiac arrest
30-day Functional Outcome in Traumatic Brain Injury Patients	Functional outcome assessed by the Glasgow Outcome Scale Extended (GOS-E) in traumatic brain injury patients (Arms 1 and 3). The GOS-E ranges from 1 (death) to 8 (upper good recovery); higher scores indicate better functional outcome.	30 days after injury
Need for Neurosurgical Intervention	Occurrence of neurosurgical intervention (e.g., craniotomy, decompressive craniectomy, intracranial pressure monitoring) within 72 hours of injury.	Within 72 hours of emergency department admission
Resuscitation Characteristics in Cardiac Arrest	No-flow time (interval without CPR) and low-flow time (duration of BLS and ALS) and their association with prehospital, 6-hour, 24-hour, and 72-hour mortality.	Up to 72 hours after cardiac arrest

Collaborators and Investigators

• Sponsor: University of Pecs
• Collaborators: Örebro University, Sweden

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: August 12, 2026
• First Submitted That Met QC Criteria: August 21, 2026
• First Posted (Actual): August 24, 2026

Study Record Updates

• Last Update Posted (Actual): August 24, 2026
• Last Update Submitted That Met QC Criteria: August 21, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Emergency Medicine; Biomarkers; Brain Injuries; Kinetics; Prehospital Emergency Care; Glial Fibrillary Acidic Protein; Acute-phase Proteins; S100 Calcium Binding Protein beta Subunit; Out-of-hospital Heart Arrest
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cardiovascular Diseases; Wounds and Injuries; Heart Diseases; Signs and Symptoms, Respiratory; Craniocerebral Trauma; Trauma, Nervous System; Hypoxia; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Brain Injuries, Traumatic; Brain Injuries; Heart Arrest; Hypoxia, Brain; Out-of-Hospital Cardiac Arrest
• Other Study ID Numbers: NNGYK/12277-2/2026; NKFI-1 ADVANCED 151273 (Other Grant/Funding Number: National Research, Development and Innovation Office (NKFI), Hungary)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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