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
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 1,000
- 主要终点
- Discriminative performance of admission plasma H3.1 for early clinical deterioration
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Plasma H3.1 nucleosome measurement (Diagnostic Test)
结局指标
主要结局
Discriminative performance of admission plasma H3.1 for early clinical deterioration
时间窗: 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.
次要结局
- 90-day all-cause mortality(90 days after ICU admission)
- 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)
- Change in SOFA-2 score at day 7(ICU admission (H0) and day 7)
- Correlation between change in SOFA-2 and change in plasma H3.1 at 72 hours(ICU admission (H0) and 72 hours (D3))
- Plasma H3.1 concentration over the first ICU week(ICU admission (H0), 6 hours, day 1, day 3 and day 7)
- Vasopressor-free days at day 28(From ICU admission to day 28)
- Ventilator-free days at day 28(From ICU admission to day 28)
- ICU length of stay(From ICU admission to ICU discharge, up to 90 days)
- Development of septic shock(From ICU admission to ICU discharge, up to 7 days)
- Venous thromboembolism events(From ICU admission to 7 days)
- Plasma H3.1 thresholds predicting poor outcomes(From ICU admission to 28 days)
- New initiation of renal replacement therapy(From ICU admission to ICU discharge, up to 7 days)
- Renal replacement therapy-free days at day 28(From ICU admission to day 28)
研究者
Charles Dehout
Consultant, PhD student
Erasme University Hospital