Nucleosome Monitoring Relevance for Outcome Prediction in Critically Ill Patients

NCT07184593 | Not Yet Recruiting

• 1 other identifier: HUB2025237
• Study Type: observational
• Target: 1,000
• Locations: 0 countries
• Sites: N/A

Brief Summary

NUROPI is a single-centre, prospective, non-interventional study in the Intensive Care Unit (ICU) of Erasme Hospital (Hôpital Universitaire de Bruxelles, Brussels, Belgium). Some critically ill patients get worse during the first days of their ICU stay. Identifying them early could allow faster escalation of care. Nucleosomes are fragments of DNA wrapped around proteins called histones. They are released into the blood when cells die or when white blood cells form neutrophil extracellular traps (NETs). High blood levels of nucleosomes may reflect inflammation, clotting activation and organ damage. This study will measure the H3.1 nucleosome in the blood of 1,000 consecutive adult ICU patients. The measurement uses a CE-marked laboratory test (Nu.Q® NETs, chemiluminescence immunoassay on the IDS-i10 analyser). No additional blood sample is taken for the study. H3.1 is measured on the leftover plasma of blood samples already drawn for routine care, at ICU admission, 6 hours, day 1, day 3 and day 7. Patient treatment is not changed. Patients, or their relatives or legal representative, receive an information notice and may refuse participation at any time. The main question is whether H3.1, alone or combined with routine ICU data, can identify patients at high risk of clinical deterioration within 72 hours of ICU admission. Other questions concern the link between H3.1 and mortality, organ dysfunction, and ICU treatments, and how H3.1 levels change during the first week.

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)

• Discriminative performance of admission plasma H3.1 for early clinical deterioration

  Area under the receiver operating characteristic curve (AUROC) of plasma H3.1 measured at ICU admission, alone and combined with routine ICU parameters, for predicting clinical deterioration. Clinical deterioration is defined as an increase of at least 2 points in the Sequential Organ Failure Assessment version 2 (SOFA-2) score from admission, or ICU death, within 72 hours of ICU admission.

  From ICU admission to 72 hours

Secondary Outcomes (16)

• 28-day all-cause mortality

  28 days after ICU admission

• Change in SOFA-2 score at 72 hours

  ICU admission (H0) and 72 hours (D3)

• Early ICU mortality

  From ICU admission to 72 hours

• ICU mortality

  From ICU admission to ICU discharge, up to 90 days

• 90-day all-cause mortality

  90 days after ICU admission

Other Outcomes (1)

• Progression to chronic kidney disease (CKD)

  At 3, 6, and 12 months after hospital discharge

Study Arms (1)

Critically ill adults (all-comers)

Consecutive adults (18 years or older) admitted to the Intensive Care Unit of Erasme Hospital within the previous 24 hours, all admission diagnoses combined, with an arterial or central venous catheter already in place for clinical reasons. Enrolment is capped at 20 neurosurgical and 50 cardiac-surgery patients. Plasma H3.1 is measured on residual routine samples at admission, 6 hours, day 1, day 3 and day 7. Pre-specified subgroup analyses include sepsis versus non-sepsis, surgical versus medical admissions, and active malignancy.

Diagnostic Test: Plasma H3.1 nucleosome measurement

Interventions

Plasma H3.1 nucleosome measurement DIAGNOSTIC_TEST

Measurement of circulating H3.1 nucleosomes by chemiluminescence immunoassay (Nu.Q® NETs on the IDS-i10 analyser, CE-marked in vitro diagnostic device) on residual plasma from routine K2-EDTA samples. No additional blood sampling is performed and results are not used for clinical management.

Critically ill adults (all-comers)

Eligibility Criteria

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

Study Population

Consecutive adult patients admitted to the Intensive Care Unit (ICU) of Erasme Hospital (Hôpital Universitaire de Bruxelles, Brussels, Belgium), all admission diagnoses combined. To avoid over-representation of elective post-operative admissions, enrolment is capped at 20 neurosurgical and 50 cardiac-surgery patients.

You may qualify if:

• Age 18 years or older
• Admission to the ICU of Erasme Hospital within the previous 24 hours, regardless of admission diagnosis
• Arterial catheter or central venous catheter already in place for clinical reasons

You may not qualify if:

• Imminent death (life expectancy less than 24 hours)
• Therapeutic limitations at ICU admission (e.g., no indication for intubation, comfort care only)
• Absence of an arterial catheter or central venous catheter
• ICU admission more than 24 hours before screening
• Readmission to the ICU of a previously enrolled patient
• Opposition to participation expressed by the patient or their legal representative

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: Consultant, PhD student

Study Record Dates

• First Submitted: August 26, 2025
• First Posted: September 22, 2025
• Study Start: October 1, 2026
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2028
• Last Updated: September 22, 2026

Record last verified: 2026-09