Nucleosome Monitoring Relevance for Outcome Prediction in Critically Ill Patients

Официальное название

Validation of a Point-of-care Device for Rapid Bedside Measurement of Circulating Nucleosome Levels in Critically Ill Patients and Study of Its Relevance to Prognostication

Обзор

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.

Подробное описание

The NuROPI study is a prospective, observational, non-interventional, monocentric study conducted in the Intensive Care Unit (ICU) of Erasme Hospital, Brussels. It aims to evaluate the association between initial levels of H3.1 nucleosomes in whole blood and 30-day mortality in critically ill patients, and to validate a novel point-of-care device for nucleosome measurement against standard chemiluminescence immunoassay (ChLIA) performed on plasma.

Inclusion requires the presence of an arterial or central venous catheter for blood sampling. Exclusion criteria include age \<18, life expectancy \<24 hours, therapeutic limitations, active cancer, absence of vascular access, ICU stay \>24h before screening, or prior inclusion. Blood will be sampled at five predefined timepoints: admission (H0), 6 hours (H6), Day 1 (D1), Day 3 (D3), and Day 7 (D7). At each timepoint, four 5 mL blood tubes will be collected during routine care, and a 20 µL aliquot will be used for immediate point-of-care H3.1 measurement. Plasma will be extracted and stored for delayed ChLIA analysis. In patients with acute brain injury and an external ventricular drain (EVD), cerebrospinal fluid (CSF) will be sampled daily until Day 5, but only if the fluid is otherwise intended to be discarded. The study seeks to establish whether nucleosome levels can serve as a biomarker for prognosis and patient stratification in critical illness.

Standard ICU data such as SOFA scores and SAPS II will be recorded, as is already routinely done in some registries like Epimed.

Data will be entered into RedCap by the research team and the investigators.

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, as defined by SEPSIS-3 criteria (approximately 30 patients) * Septic shock, per SEPSIS-3 (approximately 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 (approximately 20 patients) * Severe acute pancreatitis, requiring ICU management (approximately 10 patients) This heterogeneous ICU population is specifically chosen to evaluate the relevance of H3.1 nucleosome levels across multiple critical illness etiologies.

Objectives

Primary

\- 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.

Secondary

* To assess the correlation between nucleosome levels measured in whole blood at the point of care and traditional chemiluminescence immunoassays performed on plasma. * To validate the feasibility and reliability of a novel point-of-care device for rapid nucleosome quantification. * To determine whether nucleosome measurement is relevant across a variety of critical conditions (e.g., sepsis, septic shock, cardiogenic shock, severe trauma, cardiac arrest, acute brain injury, severe acute pancreatitis)

Первичные конечные точки

• Mortality D30 [Срок оценки: 30 days]

Вторичные конечные точки (4)

• Nucleosome measurement correlation between point-of-care and chemiluminescence immunoassays (ChLIA) [Срок оценки: At each sampling time point - Day 0 (baseline), Hour 6, Day 1, Day 3, and Day 7]
• Cerebrospinal fluid (CSF) nucleosome levels [Срок оценки: At each sampling time point - Day 0 (baseline), Hour 6, Day 1, Day 3, and Day 7]
• Prolonged organ failure [Срок оценки: Up to 28 days after enrollment]
• In-hospital mortality [Срок оценки: Through hospital discharge (average of 14 days)]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• 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
• 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
• 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
• 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
• 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
• 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
• 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, J PMID 34605781
• 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, Max PMID 29490185

Идентификаторы

NCT: NCT07184593 · HUB2025237

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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