An observational study in Sepsis, Septic Shock and Cardiac Arrest (CA), sponsored by Erasme University Hospital. Not yet recruiting. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-22.
Sponsored by Erasme University Hospital · Observational
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.
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.
1,078 studies on the registry are indexed under Shock, Septic; 232 are open to participants now.
This study's planned enrollment of 1,000 is above the median of 108 across 406 observational studies indexed under Shock, Septic.
Browse Shock, Septic studies →Erasme University Hospital is the lead sponsor of 181 studies on the registry; 35 are open to participants now.
Compared within Shock, Septic, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Sepsis. The counts are of registry records indexed under each term, refreshed daily. How we classify →
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.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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.
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.
Time frame: From ICU admission to 72 hours
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).
Time frame: 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.
Time frame: ICU admission (H0) and 72 hours (D3)
Early ICU mortality
ICU death from any cause within 72 hours of the admission sample (H0).
Time frame: From ICU admission to 72 hours
ICU mortality
Death from any cause during the ICU stay
Time frame: 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.
Time frame: 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).
Time frame: 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).
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: From ICU admission to day 28
ICU length of stay
Number of days from ICU admission to ICU discharge or death.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: From ICU admission to day 28
Progression to chronic kidney disease (CKD)
Defined as estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73m² persisting for ≥3 months, or requirement for chronic dialysis.
Time frame: At 3, 6, and 12 months after hospital discharge
No study locations are listed for this record.
Plan to share: Undecided
This study is not yet recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.