An observational study in Sepsis, sponsored by Sir Run Run Shaw Hospital. Not yet recruiting. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-10-26.
Sponsored by Sir Run Run Shaw Hospital · Observational
Sepsis is a life-threatening condition caused by a dysregulated immune response to infection, leading to organ dysfunction and increased mortality. Early diagnosis and accurate assessment of disease progression remain challenging. EMR3 (ADGRE3), a receptor expressed on the surface of neutrophils, may serve as a potential biomarker for sepsis diagnosis, immune response monitoring, and prognosis assessment. However, its clinical value requires further validation in large, multicenter prospective studies.
This multicenter, prospective, observational study will enroll approximately 3,000 adults across 8-15 hospitals in China. Participants will be classified into four groups: patients with sepsis or septic shock, patients with infection without sepsis, patients with noninfectious critical illnesses, and healthy or elective surgical controls. Neutrophil EMR3 expression will be measured using flow cytometry on residual blood samples obtained during routine clinical care. Patients with sepsis will undergo repeated measurements at baseline, 72 ± 12 hours, and day 7 ± 1 day, with an optional assessment at day 14 ± 2 days. Other participants will undergo baseline testing only. All participants will receive standard clinical care without study-related interventions or additional blood collection.
The primary outcome is the diagnostic accuracy of baseline neutrophil EMR3 expression for identifying sepsis, assessed by the area under the receiver operating characteristic curve (AUC). Secondary outcomes include changes in EMR3 expression over time, associations with 28-day all-cause mortality, septic shock, organ dysfunction, secondary infections, and intensive care unit length of stay. The study will also compare EMR3 with established biomarkers, including CD64, HLA-DR, procalcitonin, C-reactive protein, and lactate, and evaluate whether incorporating EMR3 into combined models improves diagnostic and prognostic performance. This study aims to determine whether neutrophil EMR3 can serve as a reliable biomarker for early sepsis diagnosis, disease monitoring, and risk stratification.
This study is designed to prospectively validate the clinical utility of neutrophil EMR3 (ADGRE3) expression as a biomarker for sepsis diagnosis, immune response monitoring, and prognosis assessment across multiple clinical centers in China.
Eligible participants will be consecutively recruited from intensive care units (ICUs) and emergency intensive care units (EICUs). Sepsis and septic shock will be defined according to the Sepsis-3 criteria. Final diagnostic classification will be determined by an independent adjudication committee using clinical findings, microbiological results, organ dysfunction assessments, and the overall clinical course. Committee members will be blinded to EMR3 measurements to minimize diagnostic assessment bias.
Neutrophil EMR3 expression will be quantified using standardized flow cytometry protocols, including measurements of mean fluorescence intensity and the proportion of EMR3-positive neutrophils. All participating centers will follow harmonized procedures for sample processing, antibody staining, instrument calibration, gating strategies, and quality control. Blood samples will be obtained exclusively from residual specimens collected during routine clinical care, without additional blood collection.
Longitudinal measurements will be used to characterize changes in EMR3 expression during sepsis progression and recovery. These changes will be examined in relation to clinical severity, organ dysfunction, inflammatory biomarkers, and patient outcomes. The diagnostic and prognostic performance of EMR3 will also be evaluated across clinically relevant subgroups, including different infection sites, pathogen types, age groups, immune states, and underlying diseases.
Diagnostic performance will be assessed using receiver operating characteristic curve analysis, including the area under the curve, sensitivity, specificity, and optimal cutoff values. Longitudinal changes will be analyzed using mixed-effects models or generalized estimating equations. Logistic regression and Cox proportional hazards models will be used to evaluate associations between EMR3 expression and clinical outcomes. Multivariable models incorporating EMR3 and established clinical indicators will be evaluated for discrimination, calibration, and potential clinical utility. Internal bootstrap validation and leave-one-center-out validation will be performed to assess model robustness and generalizability.
Standardized data collection, centralized quality control, and blinded outcome adjudication will be implemented to minimize measurement variability and potential bias across participating centers. The study is expected to provide multicenter evidence supporting the potential clinical application of EMR3 in sepsis diagnosis, longitudinal monitoring, and prognostic risk stratification.
1,946 studies on the registry are indexed under Sepsis; 471 are open to participants now.
This study's planned enrollment of 3,000 is above the median of 160 across 957 observational studies indexed under Sepsis.
Browse Sepsis studies →Sir Run Run Shaw Hospital is the lead sponsor of 125 studies on the registry; 65 are open to participants now.
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The study population will consist of approximately 3,000 adults aged 18 years or older recruited from 8-15 tertiary hospitals across China. Eligible participants will include patients admitted to intensive care units (ICUs) or emergency intensive care units (EICUs) with suspected or confirmed infection, sepsis, septic shock, or noninfectious critical illness, as well as healthy individuals undergoing routine health examinations or elective surgical patients serving as controls.
Participants will be classified into four cohorts: sepsis or septic shock (n=900), infection without sepsis (n=700), noninfectious critical illness (n=1,200), and healthy or elective surgical controls (n=200). Sepsis and septic shock will be defined according to the Sepsis-3 criteria, with final diagnostic classification determined by an independent adjudication committee blinded to EMR3 measurements.
Participants will be consecutively screened and enrolled according to predefined eligibility criteria. All stu
**Inclusion Criteria:**
**Exclusion Criteria:**
Patients aged 18 years or older diagnosed with sepsis or septic shock according to the Sepsis-3 criteria. Neutrophil EMR3 expression will be assessed at baseline, 72 ± 12 hours, and day 7 ± 1 day, with an optional measurement at day 14 ± 2 days, using residual blood samples from routine clinical care. Clinical outcomes will be followed for 28 days.
Adult patients with confirmed or suspected infection who do not meet the Sepsis-3 diagnostic criteria for sepsis. Neutrophil EMR3 expression will be measured at baseline using residual blood samples from routine clinical care. This group will serve as a comparator for evaluating the diagnostic accuracy of EMR3 in identifying sepsis.
Adult critically ill patients with noninfectious conditions, such as trauma, postoperative inflammation, acute pancreatitis, acute heart failure, or pulmonary embolism, without evidence of infection based on final clinical adjudication. Baseline neutrophil EMR3 expression will be measured to evaluate its diagnostic specificity in distinguishing sepsis from noninfectious critical illnesses.
Healthy adults undergoing routine health examinations or patients undergoing elective surgery who meet the study eligibility criteria. Baseline neutrophil EMR3 expression will be measured using residual blood samples to establish reference expression levels and evaluate the stability of the flow cytometry assay. This group will not be included in the primary diagnostic comparison.
Diagnostic Accuracy of Neutrophil EMR3 Expression for Sepsis
The diagnostic accuracy of baseline neutrophil EMR3 expression for identifying sepsis will be evaluated using the area under the receiver operating characteristic curve (ROC-AUC), with a 95% confidence interval. EMR3 expression will be measured by flow cytometry using residual EDTA-anticoagulated whole blood. The primary comparison will be between patients with sepsis or septic shock and patients with infection without sepsis or noninfectious critical illness. Healthy or elective surgical controls will be excluded from the primary diagnostic comparison.
Time frame: At baseline (T0), within 6 hours of enrollment or initial ICU admission.
Changes in Neutrophil EMR3 Expression Over Time
Longitudinal changes in neutrophil EMR3 expression, measured by flow cytometry, will be evaluated in patients with sepsis or septic shock. Changes in EMR3 expression will be analyzed in relation to disease severity, organ dysfunction, and established inflammatory biomarkers.
Time frame: Baseline (T0), 72 ± 12 hours (T1), Day 7 ± 1 day (T2), and optionally Day 14 ± 2 days (T3).
All-Cause Mortality at 28 Days
The proportion of patients with sepsis or septic shock who die from any cause within 28 days after enrollment. Associations between baseline EMR3 expression, longitudinal EMR3 changes, and mortality will be evaluated.
Time frame: From enrollment through Day 28.
Diagnostic Accuracy of EMR3 for Septic Shock
The ability of baseline neutrophil EMR3 expression to identify septic shock will be assessed using receiver operating characteristic curve analysis, including the area under the curve (AUC), sensitivity, and specificity. Septic shock will be defined according to Sepsis-3 criteria.
Time frame: At baseline (T0), within 6 hours of enrollment or initial ICU admission.
Association Between EMR3 Expression and Organ Dysfunction
The association between neutrophil EMR3 expression and organ dysfunction will be evaluated using Sequential Organ Failure Assessment (SOFA) scores. Longitudinal changes in EMR3 expression will be compared with changes in SOFA scores to assess their relationship with disease progression and recovery.
Time frame: Baseline, 72 ± 12 hours, and Day 7 ± 1 day; optionally Day 14 ± 2 days.
Incidence of Secondary Infections
The proportion of patients with sepsis or septic shock who develop secondary infections during hospitalization. The association between neutrophil EMR3 expression and the occurrence of secondary infections will be evaluated.
Time frame: From enrollment through Day 28.
Intensive Care Unit Length of Stay
Duration of intensive care unit hospitalization, measured in days. The association between baseline EMR3 expression, longitudinal EMR3 changes, and ICU length of stay will be assessed.
Time frame: From ICU admission to ICU discharge, assessed through Day 28.
Duration of Organ Support
Duration of organ support, including invasive mechanical ventilation, vasopressor therapy, and continuous renal replacement therapy, measured in days. Associations between EMR3 expression and organ support requirements will be evaluated.
Time frame: From enrollment through Day 28.
Incremental Predictive Value of EMR3 in Combined Models
The incremental diagnostic and prognostic value of adding EMR3 to models containing established clinical biomarkers and severity scores will be evaluated. Model performance will be compared using the area under the receiver operating characteristic curve (AUC), calibration, net reclassification improvement (NRI), and integrated discrimination improvement (IDI).
Time frame: Baseline through Day 28.
No study locations are listed for this record.
Plan to share: Undecided
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