SepsisNuROPINCT07184593
Nucleosome Monitoring Relevance for Outcome Prediction in Critically Ill Patients
An observational study of Sepsis and Septic Shock, run by Erasme University Hospital.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis, Septic Shock, Cardiac Arrest (CA)
- What is being tested?
- Plasma H3.1 nucleosome measurement
- How many people
- 1,000 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2026to 30 Sep 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: 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
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.
Read more
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.
Read the detailed description
Background Extracellular histones and nucleosomes act as damage-associated molecular patterns. They activate Toll-like receptors (TLR2, TLR4, TLR9), promote cytokine release, damage the endothelium and contribute to immunothrombosis. Circulating histone levels correlate with organ dysfunction severity in septic shock. Their prognostic value across the full spectrum of critical illness remains to be established.
Objectives Primary objective: to evaluate the clinical performance of plasma H3.1, alone or combined with routine ICU parameters, for the early identification of ICU patients at high risk of clinical deterioration requiring timely escalation of care.
Secondary objectives: to assess H3.1 as an independent prognostic marker of 28-day mortality after adjustment for established severity scores (Sequential Organ Failure Assessment version 2 [SOFA-2], Simplified Acute Physiology Score II [SAPS II]); to describe H3.1 kinetics over the first ICU week; to assess associations between H3.1 and organ dysfunction, vasopressor requirements, mechanical ventilation, renal replacement therapy (RRT) and venous thromboembolism (VTE); to compare H3.1 levels across diagnostic subgroups; to explore interactions between H3.1 and ICU therapies (anticoagulation, dexmedetomidine, corticosteroids, RRT, extracorporeal membrane oxygenation [ECMO]); to assess H3.1 as a potential enrichment biomarker for future trials targeting extracellular histones.
Design Prospective, non-interventional, single-centre diagnostic-prognostic derivation and internal validation study. No procedure is performed for research purposes. H3.1 is measured on residual plasma (at least 100 µL) from routine K2-EDTA samples drawn through an arterial or central venous catheter already in place. Timepoints: ICU admission (H0), 6 hours (H6), day 1 (D1), day 3 (D3) and day 7 (D7). Plasma is analysed in batches by chemiluminescence immunoassay (Nu.Q® NETs, IDS-i10) and is not stored or biobanked beyond the study analyses. Participation is based on a non-opposition procedure. A deferred procedure may be used when neither the patient nor a representative can be informed at inclusion. Routine clinical data (including SOFA-2 and SAPS II) are recorded in REDCap.
Population 1,000 consecutive adults admitted to the ICU within the previous 24 hours, all admission diagnoses combined. Enrolment is capped at 20 neurosurgical and 50 cardiac-surgery patients. Patients with active malignancy are included and analysed as a pre-specified subgroup.
Primary endpoint Clinical deterioration, defined as an increase in SOFA-2 score of at least 2 points from admission within 72 hours, or ICU death within 72 hours.
Secondary endpoints ICU, 28-day and 90-day all-cause mortality; vasopressor duration; mechanical ventilation duration; development of septic shock; ICU length of stay; VTE events; the primary composite endpoint at 48 hours; change in SOFA-2 from admission to day 7 (or ICU discharge if earlier); correlation between the change in SOFA-2 and the change in H3.1 from admission to 72 hours; H3.1 thresholds predicting poor outcomes across subgroups.
Sample size and analysis The expected prevalence of the primary endpoint is 20% to 35%. With a null area under the receiver operating characteristic curve (AUROC) of 0.50, an anticipated AUROC of 0.75 and a two-sided alpha of 0.05, 1,000 patients provide more than 90% power across this range (Hanley and McNeil, 1982). At a central prevalence of 25%, about 250 events are expected, supporting up to 25 candidate predictors (at least 10 events per variable). An interim analysis is planned at 500 patients. Internal validation will use bootstrap resampling (1,000 iterations). A pre-specified sensitivity analysis will exclude patients with an admission SOFA-2 score of 15 or more. Reporting will follow STARD 2015 for H3.1 as a stand-alone test and TRIPOD 2024 for the combined prognostic model.
- Conditions
- Sepsis, Septic Shock, Cardiac Arrest (CA), Pancreatitis, Acute Brain Injury, Trauma Blunt
- Being tested
- Plasma H3.1 nucleosome measurement
- Keywords
- nucleosome, septic shock, Histones, Cardiac Arrest, Cardiogenic shock, Trauma, Acute brain injury
- Medical subject headings
- Sepsis, Shock, Septic, Heart Arrest, Pancreatitis, Brain Injuries, Wounds, Nonpenetrating, Shock, Cardiogenic, Wounds and Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Plasma H3.1 nucleosome measurementDiagnostic 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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Diagnostic Test: Plasma H3.1 nucleosome measurement |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From ICU admission to 72 hours
Secondary outcomes (16)
28-day all-cause mortality
Death from any cause within 28 days of ICU admission. Association with admission H3.1 will be assessed after adjustment for SOFA-2 and Simplified Acute Physiology Score II (SAPS II).
Measured: 28 days after ICU admission
Change in SOFA-2 score at 72 hours
Difference between SOFA-2 score at 72 hours (D3) and SOFA-2 score at ICU admission (H0), analysed as a continuous variable and as an increase of at least 2 points. Assessed in patients still in the ICU at 72 hours.
Measured: ICU admission (H0) and 72 hours (D3)
Early ICU mortality
ICU death from any cause within 72 hours of the admission sample (H0).
Measured: From ICU admission to 72 hours
ICU mortality
Death from any cause during the ICU stay
Measured: From ICU admission to ICU discharge, up to 90 days
90-day all-cause mortality
Death from any cause within 90 days of ICU admission.
Measured: 90 days after ICU admission
Change in SOFA-2 score at day 7
Difference between the SOFA-2 score at day 7 (or at ICU discharge if earlier) and at ICU admission (H0).
Measured: ICU admission (H0) and day 7
Correlation between change in SOFA-2 and change in plasma H3.1 at 72 hours
Correlation between the change in SOFA-2 score and the change in plasma H3.1 concentration from ICU admission (H0) to 72 hours (D3).
Measured: ICU admission (H0) and 72 hours (D3)
Plasma H3.1 concentration over the first ICU week
Plasma H3.1 nucleosome concentration (ng/mL) measured by chemiluminescence immunoassay (Nu.Q® NETs, IDS-i10).
Measured: ICU admission (H0), 6 hours, day 1, day 3 and day 7
Vasopressor-free days at day 28
Number of days alive and free of vasopressor therapy (noradrenaline or vasopressin) from ICU admission to day 28. Patients who die before day 28 are assigned 0 days.
Measured: From ICU admission to day 28
Ventilator-free days at day 28
Number of days alive and free of invasive mechanical ventilation from ICU admission to day 28. Patients who die before day 28 are assigned 0 days.
Measured: From ICU admission to day 28
ICU length of stay
Number of days from ICU admission to ICU discharge or death.
Measured: From ICU admission to ICU discharge, up to 90 days
Development of septic shock
New onset of septic shock according to Sepsis-3 criteria during the ICU stay, in patients admitted without septic shock.
Measured: From ICU admission to ICU discharge, up to 7 days
Venous thromboembolism events
Occurrence of deep vein thrombosis or pulmonary embolism, confirmed by Doppler ultrasound, computed tomography pulmonary angiography, or clinical assessment with D-dimer.
Measured: From ICU admission to 7 days
Plasma H3.1 thresholds predicting poor outcomes
Plasma H3.1 cut-off values associated with 28-day mortality and with the primary composite endpoint, overall and in pre-specified subgroups (sepsis versus non-sepsis, surgical versus medical admissions, active malignancy).
Measured: From ICU admission to 28 days
New initiation of renal replacement therapy
Initiation of renal replacement therapy (RRT) during the ICU stay, in patients not receiving chronic dialysis before ICU admission.
Measured: From ICU admission to ICU discharge, up to 7 days
Renal replacement therapy-free days at day 28
Number of days alive and free of RRT from ICU admission to day 28, in patients not receiving chronic dialysis before ICU admission. Patients who die before day 28 are assigned 0 days.
Measured: From ICU admission to day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2025
- Study start1 Oct 2026 (estimated)
- Primary completion30 Sep 2028 (estimated)
- Study completion30 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Erasme University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Charles Dehout, Erasme University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07184593
- Sponsor's protocol ID
- HUB2025237
- Acronym
- NuROPI
- Status last verified
- Sep 2026
- First submitted
- 26 Aug 2025
- Last updated
- 22 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 39061959Garcia 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.
PubMed 38001494Allam 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.
PubMed 24706102Cheng 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.
PubMed 31162199Silk 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.
PubMed 28542146Yang 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.
PubMed 39206200Evans 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.
PubMed 34605781Annane 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.
PubMed 29490185Ranieri 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.
PubMed 22616830Tindal 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.
PubMed 33641552Singer 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.
PubMed 26903338
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07184593
- Acronym / sponsor ID
- NuROPI / HUB2025237
- Conditions
- Sepsis, Septic Shock, Cardiac Arrest (CA), Pancreatitis, Acute Brain Injury, Trauma Blunt
- Keywords
- nucleosome, septic shock, Histones, Cardiac Arrest, Cardiogenic shock, Trauma, Acute brain injury
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- Erasme University HospitalUniversity, hospital or other
- Study start
- 1 Oct 2026 (estimated)
- Primary completion
- 30 Sep 2028 (estimated)
- Study completion
- 30 Sep 2028 (estimated)
- First posted
- 22 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Background Extracellular histones and nucleosomes act as damage-associated molecular patterns. They activate Toll-like receptors (TLR2, TLR4, TLR9), promote cytokine release, damage the endothelium and contribute to immunothrombosis. Circulating histone levels correlate with organ dysfunction severity in septic shock. Their prognostic value across the full spectrum of critical illness remains to be established.
Objectives Primary objective: to evaluate the clinical performance of plasma H3.1, alone or combined with routine ICU parameters, for the early identification of ICU patients at high risk of clinical deterioration requiring timely escalation of care.
Secondary objectives: to assess H3.1 as an independent prognostic marker of 28-day mortality after adjustment for established severity scores (Sequential Organ Failure Assessment version 2 [SOFA-2], Simplified Acute Physiology Score II [SAPS II]); to describe H3.1 kinetics over the first ICU week; to assess associations between H3.1 and organ dysfunction, vasopressor requirements, mechanical ventilation, renal replacement therapy (RRT) and venous thromboembolism (VTE); to compare H3.1 levels across diagnostic subgroups; to explore interactions between H3.1 and ICU therapies (anticoagulation, dexmedetomidine, corticosteroids, RRT, extracorporeal membrane oxygenation [ECMO]); to assess H3.1 as a potential enrichment biomarker for future trials targeting extracellular histones.
Design Prospective, non-interventional, single-centre diagnostic-prognostic derivation and internal validation study. No procedure is performed for research purposes. H3.1 is measured on residual plasma (at least 100 µL) from routine K2-EDTA samples drawn through an arterial or central venous catheter already in place. Timepoints: ICU admission (H0), 6 hours (H6), day 1 (D1), day 3 (D3) and day 7 (D7). Plasma is analysed in batches by chemiluminescence immunoassay (Nu.Q® NETs, IDS-i10) and is not stored or biobanked beyond the study analyses. Participation is based on a non-opposition procedure. A deferred procedure may be used when neither the patient nor a representative can be informed at inclusion. Routine clinical data (including SOFA-2 and SAPS II) are recorded in REDCap.
Population 1,000 consecutive adults admitted to the ICU within the previous 24 hours, all admission diagnoses combined. Enrolment is capped at 20 neurosurgical and 50 cardiac-surgery patients. Patients with active malignancy are included and analysed as a pre-specified subgroup.
Primary endpoint Clinical deterioration, defined as an increase in SOFA-2 score of at least 2 points from admission within 72 hours, or ICU death within 72 hours.
Secondary endpoints ICU, 28-day and 90-day all-cause mortality; vasopressor duration; mechanical ventilation duration; development of septic shock; ICU length of stay; VTE events; the primary composite endpoint at 48 hours; change in SOFA-2 from admission to day 7 (or ICU discharge if earlier); correlation between the change in SOFA-2 and the change in H3.1 from admission to 72 hours; H3.1 thresholds predicting poor outcomes across subgroups.
Sample size and analysis The expected prevalence of the primary endpoint is 20% to 35%. With a null area under the receiver operating characteristic curve (AUROC) of 0.50, an anticipated AUROC of 0.75 and a two-sided alpha of 0.05, 1,000 patients provide more than 90% power across this range (Hanley and McNeil, 1982). At a central prevalence of 25%, about 250 events are expected, supporting up to 25 candidate predictors (at least 10 events per variable). An interim analysis is planned at 500 patients. Internal validation will use bootstrap resampling (1,000 iterations). A pre-specified sensitivity analysis will exclude patients with an admission SOFA-2 score of 15 or more. Reporting will follow STARD 2015 for H3.1 as a stand-alone test and TRIPOD 2024 for the combined prognostic model.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Critically ill adults (all-comers) | – | Diagnostic Test: Plasma H3.1 nucleosome measurementConsecutive 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Plasma H3.1 nucleosome measurementMeasurement 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. | Diagnostic test | Critically ill adults (all-comers) |
Primary outcome
Discriminative performance of admission plasma H3.1 for early clinical deterioration
Time frame: From ICU admission to 72 hours
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.
16 secondary outcomes
28-day all-cause mortality
Time frame: 28 days after ICU admission
Change in SOFA-2 score at 72 hours
Time frame: ICU admission (H0) and 72 hours (D3)
Early ICU mortality
Time frame: From ICU admission to 72 hours
ICU mortality
Time frame: From ICU admission to ICU discharge, up to 90 days
90-day all-cause mortality
Time frame: 90 days after ICU admission
Change in SOFA-2 score at day 7
Time frame: ICU admission (H0) and day 7
Correlation between change in SOFA-2 and change in plasma H3.1 at 72 hours
Time frame: ICU admission (H0) and 72 hours (D3)
Plasma H3.1 concentration over the first ICU week
Time frame: ICU admission (H0), 6 hours, day 1, day 3 and day 7
Vasopressor-free days at day 28
Time frame: From ICU admission to day 28
Ventilator-free days at day 28
Time frame: From ICU admission to day 28
ICU length of stay
Time frame: From ICU admission to ICU discharge, up to 90 days
Development of septic shock
Time frame: From ICU admission to ICU discharge, up to 7 days
Venous thromboembolism events
Time frame: From ICU admission to 7 days
Plasma H3.1 thresholds predicting poor outcomes
Time frame: From ICU admission to 28 days
New initiation of renal replacement therapy
Time frame: From ICU admission to ICU discharge, up to 7 days
Renal replacement therapy-free days at day 28
Time frame: From ICU admission to day 28
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2026.
- Background: PubMed 39061959Su 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.
- Background: PubMed 38001494Garcia 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.
- Background: PubMed 24706102Allam 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.
- Background: PubMed 31162199Cheng 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.
- Background: PubMed 28542146Silk 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.
- Background: PubMed 39206200Yang 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.
- Background: PubMed 34605781Evans 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.
- Background: PubMed 29490185Annane 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.
- Background: PubMed 22616830Ranieri 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.
- Background: PubMed 33641552Tindal 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.
- Background: PubMed 26903338Singer 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
An observational study of Sepsis and Septic Shock, run by Erasme University Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 22 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Charls Dehout, M.D (+32 2 555 6589, charles.dehout@hubruxelles.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Discriminative performance of admission plasma H3.1 for early clinical deterioration (time frame: From ICU admission to 72 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07184593, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2026.