Nucleosome Monitoring Relevance for Outcome Prediction in Critically Ill Patients

NCT07184593 | Not Yet Recruiting

• 1 other identifier: HUB2025237
• Study Type: observational
• Target: 130
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this observational study is to evaluate whether whole blood H3.1 nucleosome levels can predict 30-day mortality in adult critically ill patients admitted to the ICU with conditions such as sepsis, septic shock, cardiogenic shock, severe trauma, post-cardiac arrest, acute brain injury, or severe acute pancreatitis. The main questions it aims to answer are: Do initial whole blood H3.1 nucleosome levels predict 30-day mortality in critically ill patients? Are whole blood nucleosome measurements using a novel point-of-care device correlated with traditional plasma chemiluminescence immunoassays (ChLIA)? If there is a comparison group: Researchers will compare point-of-care whole blood nucleosome results with plasma ChLIA assays to see if the device provides reliable and feasible bedside measurements. Participants will: Provide blood samples at admission, 6h, Day 1, Day 3, and Day 7 for nucleosome analysis. Undergo point-of-care H3.1 nucleosome measurement and parallel plasma storage for ChLIA testing. (If applicable, in acute brain injury patients with external ventricular drains) provide daily cerebrospinal fluid samples until Day 5, only if otherwise discarded. Have standard ICU data (SOFA, SAPS II, etc.) collected as part of routine care.

Conditions

Sepsis; Septic Shock; Cardiac Arrest (CA); Pancreatitis; Acute Brain Injury; Trauma Blunt; Cardiogenic Shock

Keywords

nucleosome; septic shock; Histones; Cardiac Arrest; Cardiogenic shock; Trauma; Acute brain injury

Outcome Measures

Primary Outcomes (1)

• Mortality D30

  To evaluate the association between initial levels of H3.1 nucleosomes in whole blood and 30-day mortality in a cohort of critically ill patients.

  30 days

Secondary Outcomes (4)

• Nucleosome measurement correlation between point-of-care and chemiluminescence immunoassays (ChLIA)

  At each sampling time point - Day 0 (baseline), Hour 6, Day 1, Day 3, and Day 7

• Cerebrospinal fluid (CSF) nucleosome levels

  At each sampling time point - Day 0 (baseline), Hour 6, Day 1, Day 3, and Day 7

• Prolonged organ failure

  Up to 28 days after enrollment

• In-hospital mortality

  Through hospital discharge (average of 14 days)

Other Outcomes (1)

• Progression to chronic kidney disease (CKD)

  At 3, 6, and 12 months after hospital discharge

Study Arms (7)

Sepsis

As defined by sepsis-3 definition (excluding septic shock, around 30 patients)

Septic shock

as defined per SEPSIS-3 definition (around 30 patients)

Cardiogenic shock

classified as at least SCAI stage C (approximately 10 patients)

Severe trauma

Requiring at least 4 units of red blood cells within 6 hours post-admission (approximately 10 patients)

Acute brain injury

requiring invasive neuromonitoring (approximately 20 patients)

Post-cardiac arrest

With at least 15 minutes of no or low perfusion (intra or extra hospital setting) (approximately 20 patients)

Severe acute pancreatitis

requiring ICU management (approximately 10 patients)

Eligibility Criteria

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

Study Population

The study population will consist of 130 adult critically ill patients admitted to the Intensive Care Unit (ICU) of Erasme Hospital. Eligible participants must be 18 years or older and admitted to the ICU within the past 24 hours. All patients must have arterial or central venous access for blood sampling. The population will include a diverse group of critically ill individuals representing various acute conditions commonly encountered in intensive care: Sepsis Septic shock Cardiogenic shock Severe trauma Acute brain injury Severe trauma Post-cardiac arrest shock Severe pancreatitis

You may qualify if:

• Admission to the intensive care unit (ICU) within the past 24 hours.
• Patient must meet one of the following conditions:
• Sepsis, defined according to SEPSIS-3 criteria.
• Septic shock, defined according to SEPSIS-3 criteria.
• Cardiogenic shock, classified as Stage C according to the Society for Cardiovascular Angiography and Interventions (SCAI).
• Severe trauma requiring transfusion of four or more units of red blood cells within six hours.
• Acute brain injury requiring invasive neuromonitoring.
• Post-cardiac arrest with at least 15 minutes of no or low perfusion.
• Severe acute pancreatitis requiring ICU-level care.
• \- Presence of an arterial or central venous catheter to allow blood sampling.

You may not qualify if:

• Patient who has expressed opposition to participate.
• Age younger than 18 years.
• Imminent death with an expected survival of less than 24 hours.
• Presence of therapeutic limitations (e.g., no indication for intubation).
• Active cancer.
• Absence of the required vascular access.
• ICU admission longer than 24 hours prior to screening.
• Readmission of a previously enrolled patient.

Sponsors & Collaborators

• Erasme University Hospital: lead

Related Publications (11)

• Su F, Moreau A, Savi M, Salvagno M, Annoni F, Zhao L, Xie K, Vincent JL, Taccone FS. Circulating Nucleosomes as a Novel Biomarker for Sepsis: A Scoping Review. Biomedicines. 2024 Jun 21;12(7):1385. doi: 10.3390/biomedicines12071385.

  PMID: 39061959 BACKGROUND

• Garcia B, Su F, Dewachter L, Wang Y, Li N, Remmelink M, Eycken MV, Khaldi A, Favory R, Herpain A, Moreau A, Moiroux-Sahraoui A, Manicone F, Annoni F, Shi L, Vincent JL, Creteur J, Taccone FS. Neutralization of extracellular histones by sodium-Beta-O-methyl cellobioside sulfate in septic shock. Crit Care. 2023 Nov 24;27(1):458. doi: 10.1186/s13054-023-04741-x.

  PMID: 38001494 BACKGROUND

• Allam R, Kumar SV, Darisipudi MN, Anders HJ. Extracellular histones in tissue injury and inflammation. J Mol Med (Berl). 2014 May;92(5):465-72. doi: 10.1007/s00109-014-1148-z. Epub 2014 Apr 6.

  PMID: 24706102 BACKGROUND

• Cheng Z, Abrams ST, Alhamdi Y, Toh J, Yu W, Wang G, Toh CH. Circulating Histones Are Major Mediators of Multiple Organ Dysfunction Syndrome in Acute Critical Illnesses. Crit Care Med. 2019 Aug;47(8):e677-e684. doi: 10.1097/CCM.0000000000003839.

  PMID: 31162199 BACKGROUND

• Silk E, Zhao H, Weng H, Ma D. The role of extracellular histone in organ injury. Cell Death Dis. 2017 May 25;8(5):e2812. doi: 10.1038/cddis.2017.52.

  PMID: 28542146 BACKGROUND

• Yang T, Peng J, Zhang Z, Chen Y, Liu Z, Jiang L, Jin L, Han M, Su B, Li Y. Emerging therapeutic strategies targeting extracellular histones for critical and inflammatory diseases: an updated narrative review. Front Immunol. 2024 Aug 14;15:1438984. doi: 10.3389/fimmu.2024.1438984. eCollection 2024.

  PMID: 39206200 BACKGROUND

• Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, Mcintyre L, Ostermann M, Prescott HC, Schorr C, Simpson S, Wiersinga WJ, Alshamsi F, Angus DC, Arabi Y, Azevedo L, Beale R, Beilman G, Belley-Cote E, Burry L, Cecconi M, Centofanti J, Coz Yataco A, De Waele J, Dellinger RP, Doi K, Du B, Estenssoro E, Ferrer R, Gomersall C, Hodgson C, Hylander Moller M, Iwashyna T, Jacob S, Kleinpell R, Klompas M, Koh Y, Kumar A, Kwizera A, Lobo S, Masur H, McGloughlin S, Mehta S, Mehta Y, Mer M, Nunnally M, Oczkowski S, Osborn T, Papathanassoglou E, Perner A, Puskarich M, Roberts J, Schweickert W, Seckel M, Sevransky J, Sprung CL, Welte T, Zimmerman J, Levy M. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med. 2021 Nov 1;49(11):e1063-e1143. doi: 10.1097/CCM.0000000000005337. No abstract available.

  PMID: 34605781 BACKGROUND

• Annane D, Renault A, Brun-Buisson C, Megarbane B, Quenot JP, Siami S, Cariou A, Forceville X, Schwebel C, Martin C, Timsit JF, Misset B, Ali Benali M, Colin G, Souweine B, Asehnoune K, Mercier E, Chimot L, Charpentier C, Francois B, Boulain T, Petitpas F, Constantin JM, Dhonneur G, Baudin F, Combes A, Bohe J, Loriferne JF, Amathieu R, Cook F, Slama M, Leroy O, Capellier G, Dargent A, Hissem T, Maxime V, Bellissant E; CRICS-TRIGGERSEP Network. Hydrocortisone plus Fludrocortisone for Adults with Septic Shock. N Engl J Med. 2018 Mar 1;378(9):809-818. doi: 10.1056/NEJMoa1705716.

  PMID: 29490185 BACKGROUND

• Ranieri VM, Thompson BT, Barie PS, Dhainaut JF, Douglas IS, Finfer S, Gardlund B, Marshall JC, Rhodes A, Artigas A, Payen D, Tenhunen J, Al-Khalidi HR, Thompson V, Janes J, Macias WL, Vangerow B, Williams MD; PROWESS-SHOCK Study Group. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med. 2012 May 31;366(22):2055-64. doi: 10.1056/NEJMoa1202290. Epub 2012 May 22.

  PMID: 22616830 BACKGROUND

• Tindal EW, Armstead BE, Monaghan SF, Heffernan DS, Ayala A. Emerging therapeutic targets for sepsis. Expert Opin Ther Targets. 2021 Mar;25(3):175-189. doi: 10.1080/14728222.2021.1897107. Epub 2021 Apr 12.

  PMID: 33641552 BACKGROUND

• Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.

  PMID: 26903338 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Plasma, serum and cerebrospinal fluid of patients at 5 different timepoints.

MeSH Terms

Conditions

Sepsis; Shock, Septic; Heart Arrest; Pancreatitis; Brain Injuries; Wounds, Nonpenetrating; Shock, Cardiogenic; Wounds and Injuries

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Heart Diseases; Cardiovascular Diseases; Pancreatic Diseases; Digestive System Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Myocardial Infarction; Myocardial Ischemia; Vascular Diseases; Infarction; Ischemia; Necrosis

Central Study Contacts

Charls Dehout, M.D

CONTACT

+32 2 555 6589; charles.dehout@hubruxelles.be

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending physician, PhD student

Study Record Dates

• First Submitted: August 26, 2025
• First Posted: September 22, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2027
• Last Updated: September 22, 2025

Record last verified: 2025-09