SepsisEMR3-SEPSISNCT07896018
Clinical Value of EMR3 in Sepsis Diagnosis, Monitoring, and Prognosis: A Multicenter Prospective Observational Study
An observational study of Sepsis, run by Sir Run Run Shaw Hospital at 1 site in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Sepsis
- How many people
- 3,000 participants
- Where
- 1 siteChina
- Study dates
- Nov 2026to Sep 2027
- How long will I take part?
- 28 Days
- 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
- Healthy volunteers accepted
- Adult, Older adult
Study population: 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
Who may be able to join
- Age ≥18 years.
- Patients admitted for the first time to the ICU or emergency ICU (EICU) of a participating center during the study period, including patients with suspected or confirmed infection, sepsis, septic shock, or noninfectious critical illness. Healthy volunteers undergoing routine health examinations may also be included as controls.
- Availability of residual EDTA-anticoagulated whole blood from routine clinical testing at enrollment, suitable for flow cytometry within the predefined testing window.
- Provision of written informed consent by the participant or a legally authorized representative, with an independent witness when required.
- Ability to complete baseline clinical data collection and 28-day outcome follow-up, as determined by the investigator.
- Expected survival of more than 72 hours.
Who cannot join
- Receipt of chemotherapy, chimeric antigen receptor T-cell (CAR-T) therapy, hematopoietic stem cell transplantation, or high-dose immunosuppressive therapy within 30 days before enrollment. Participants included in a predefined exploratory immunosuppression subgroup will be excluded from the primary diagnostic analysis.
- Active hematological malignancy, severe granulocytopenia, or absolute neutrophil count <0.5 × 10⁹/L that may interfere with the interpretation of myeloid cell phenotypes.
- Known uncontrolled HIV infection, systemic lupus erythematosus, or long-term systemic corticosteroid or immunomodulatory therapy considered by the investigator to substantially affect the primary analysis.
- Pregnancy or breastfeeding.
- Severely hemolyzed or clotted blood samples, sample identification errors, processing beyond the permitted time window, or missing critical clinical data preventing outcome adjudication.
- Refusal by the participant or legally authorized representative to permit the use of residual blood samples and clinical data.
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- Expected survival of less than 72 hours.
- A documented decision by the participant or family to withhold or limit active treatment.
- Membership in vulnerable populations other than those specifically permitted by the protocol (patients with cognitive impairment, critically ill patients, older adults, and individuals unable to read), including individuals with psychiatric disorders.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
MA YILEI contact
China1 site, 1 recruiting
- Recruiting
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310016
jiancang zhou, 13867413145, jiancangzhou@zju.edu.cn
About this study
Official title: Clinical Value of EMR3 in Early Diagnosis, Dynamic Monitoring, and Prognostic Assessment of Sepsis: A Multicenter Prospective Observational Study in China
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.
Read the detailed description
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.
- Conditions
- Sepsis
- Keywords
- Sepsis, Septic Shock, EMR3, ADGRE3, Neutrophils, Biomarkers, Flow Cytometry, Early Diagnosis, Immune Monitoring
- Medical subject headings
- Sepsis, Shock, Septic, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Sepsis/Septic Shock | 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. | |
| Infection Without Sepsis | 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. | |
| Noninfectious Critical Illness | 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 or Elective Surgical Controls | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At baseline (T0), within 6 hours of enrollment or initial ICU admission.
Secondary outcomes (8)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: Baseline through Day 28.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2026
- Study startNov 2026 (estimated)
- Primary completionJun 2027 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- More trials run by Sir Run Run Shaw HospitalThe sponsor's other registered studies.
- 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
- 3,000 participants (estimated)
- Target duration
- 28 Days
Sponsor and investigators
- Lead sponsor
- Sir Run Run Shaw Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jian-cang Zhou M.D., Sir Run Run Shaw Hospital
- Investigators
- ZHOU JIANCANG, Principal investigator, Sir Run Run Shaw Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07896018
- Sponsor's protocol ID
- SRRSH2026-0860
- Other IDs
- MR-33-26-075995
- Acronym
- EMR3-SEPSIS
- Status last verified
- Oct 2026
- First submitted
- 19 Oct 2026
- Last updated
- 28 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Standing Committee of the National People's Congress of the People's Republic of China. Data Security Law of the People's Republic of China. June 10, 2021.
Standing Committee of the National People's Congress of the People's Republic of China. Personal Information Protection Law of the People's Republic of China. August 20, 2021.
Ministry of Science and Technology of the People's Republic of China. Implementing Rules for the Regulations on the Administration of Human Genetic Resources. 2023.
State Council of the People's Republic of China. Regulations of the People's Republic of China on the Administration of Human Genetic Resources. 2019.
National Health Commission of the People's Republic of China, Ministry of Education, Ministry of Science and Technology, and National Administration of Traditional Chinese Medicine. Measures for the Ethical Review of Life Science and Medical Research Involving Humans. 2023.
Ma Y, Yu P, Wang X, Chen R, Ni W, Liu H, Fang X, Zhao F, Hu Q, Qiao S, Yang S, Jin H, Song J, Zhao D, Fang L, Zhang J, Zhou J. Neutrophil EMR3 dynamics in critically ill patients with sepsis: an ICU experience. Crit Care. 2026 Jun 27;30(1):336. doi: 10.1186/s13054-026-06171-x. No abstract available.
PubMed 42365378Venet F, Monneret G. Advances in the understanding and treatment of sepsis-induced immunosuppression. Nat Rev Nephrol. 2018 Feb;14(2):121-137. doi: 10.1038/nrneph.2017.165. Epub 2017 Dec 11.
PubMed 29225343Wang X, Li ZY, Zeng L, Zhang AQ, Pan W, Gu W, Jiang JX. Neutrophil CD64 expression as a diagnostic marker for sepsis in adult patients: a meta-analysis. Crit Care. 2015 Jun 10;19(1):245. doi: 10.1186/s13054-015-0972-z.
PubMed 26059345Matmati M, Pouwels W, van Bruggen R, Jansen M, Hoek RM, Verhoeven AJ, Hamann J. The human EGF-TM7 receptor EMR3 is a marker for mature granulocytes. J Leukoc Biol. 2007 Feb;81(2):440-8. doi: 10.1189/jlb.0406276. Epub 2006 Nov 15.
PubMed 17108056Povoa P, Coelho L, Dal-Pizzol F, Ferrer R, Huttner A, Conway Morris A, Nobre V, Ramirez P, Rouze A, Salluh J, Singer M, Sweeney DA, Torres A, Waterer G, Kalil AC. How to use biomarkers of infection or sepsis at the bedside: guide to clinicians. Intensive Care Med. 2023 Feb;49(2):142-153. doi: 10.1007/s00134-022-06956-y. Epub 2023 Jan 2.
PubMed 36592205Evans 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, Moller MH, 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. Intensive Care Med. 2021 Nov;47(11):1181-1247. doi: 10.1007/s00134-021-06506-y. Epub 2021 Oct 2. No abstract available.
PubMed 34599691Singer 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 28 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Value of EMR3 in Early Diagnosis, Dynamic Monitoring, and Prognostic Assessment of Sepsis: A Multicenter Prospective Observational Study in China
- ClinicalTrials.gov ID
- NCT07896018
- Acronym / sponsor ID
- EMR3-SEPSIS / SRRSH2026-0860
- Conditions
- Sepsis
- Keywords
- Sepsis, Septic Shock, EMR3, ADGRE3, Neutrophils, Biomarkers, Flow Cytometry, Early Diagnosis
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 3,000 participants (estimated)
- Lead sponsor
- Sir Run Run Shaw HospitalUniversity, hospital or other
- Study start
- Nov 2026 (estimated)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Sep 2027 (estimated)
- First posted
- 26 Oct 2026 (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.
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.
Detailed description
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 28 Days
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Sepsis/Septic Shock | – | –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. |
| Infection Without Sepsis | – | –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. |
| Noninfectious Critical Illness | – | –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 or Elective Surgical Controls | – | –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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- 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
Key inclusion criteria (6 listed)
- Age ≥18 years.
- Patients admitted for the first time to the ICU or emergency ICU (EICU) of a participating center during the study period, including patients with suspected or confirmed infection, sepsis, septic shock, or noninfectious critical illness. Healthy volunteers undergoing routine health examinations may also be included as controls.
- Availability of residual EDTA-anticoagulated whole blood from routine clinical testing at enrollment, suitable for flow cytometry within the predefined testing window.
- Provision of written informed consent by the participant or a legally authorized representative, with an independent witness when required.
- Ability to complete baseline clinical data collection and 28-day outcome follow-up, as determined by the investigator.
Key exclusion criteria (9 listed)
- Receipt of chemotherapy, chimeric antigen receptor T-cell (CAR-T) therapy, hematopoietic stem cell transplantation, or high-dose immunosuppressive therapy within 30 days before enrollment. Participants included in a predefined exploratory immunosuppression subgroup will be excluded from the primary diagnostic analysis.
- Active hematological malignancy, severe granulocytopenia, or absolute neutrophil count <0.5 × 10⁹/L that may interfere with the interpretation of myeloid cell phenotypes.
- Known uncontrolled HIV infection, systemic lupus erythematosus, or long-term systemic corticosteroid or immunomodulatory therapy considered by the investigator to substantially affect the primary analysis.
- Pregnancy or breastfeeding.
- Severely hemolyzed or clotted blood samples, sample identification errors, processing beyond the permitted time window, or missing critical clinical data preventing outcome adjudication.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Diagnostic Accuracy of Neutrophil EMR3 Expression for Sepsis
Time frame: At baseline (T0), within 6 hours of enrollment or initial ICU admission.
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.
8 secondary outcomes
Changes in Neutrophil EMR3 Expression Over Time
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
Time frame: From enrollment through Day 28.
Diagnostic Accuracy of EMR3 for Septic Shock
Time frame: At baseline (T0), within 6 hours of enrollment or initial ICU admission.
Association Between EMR3 Expression and Organ Dysfunction
Time frame: Baseline, 72 ± 12 hours, and Day 7 ± 1 day; optionally Day 14 ± 2 days.
Incidence of Secondary Infections
Time frame: From enrollment through Day 28.
Intensive Care Unit Length of Stay
Time frame: From ICU admission to ICU discharge, assessed through Day 28.
Duration of Organ Support
Time frame: From enrollment through Day 28.
Incremental Predictive Value of EMR3 in Combined Models
Time frame: Baseline through 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 28 Oct 2026.
- BackgroundStanding Committee of the National People's Congress of the People's Republic of China. Data Security Law of the People's Republic of China. June 10, 2021.
- BackgroundStanding Committee of the National People's Congress of the People's Republic of China. Personal Information Protection Law of the People's Republic of China. August 20, 2021.
- BackgroundMinistry of Science and Technology of the People's Republic of China. Implementing Rules for the Regulations on the Administration of Human Genetic Resources. 2023.
- BackgroundState Council of the People's Republic of China. Regulations of the People's Republic of China on the Administration of Human Genetic Resources. 2019.
- BackgroundNational Health Commission of the People's Republic of China, Ministry of Education, Ministry of Science and Technology, and National Administration of Traditional Chinese Medicine. Measures for the Ethical Review of Life Science and Medical Research Involving Humans. 2023.
- Background: PubMed 42365378Ma Y, Yu P, Wang X, Chen R, Ni W, Liu H, Fang X, Zhao F, Hu Q, Qiao S, Yang S, Jin H, Song J, Zhao D, Fang L, Zhang J, Zhou J. Neutrophil EMR3 dynamics in critically ill patients with sepsis: an ICU experience. Crit Care. 2026 Jun 27;30(1):336. doi: 10.1186/s13054-026-06171-x. No abstract available.
- Background: PubMed 29225343Venet F, Monneret G. Advances in the understanding and treatment of sepsis-induced immunosuppression. Nat Rev Nephrol. 2018 Feb;14(2):121-137. doi: 10.1038/nrneph.2017.165. Epub 2017 Dec 11.
- Background: PubMed 26059345Wang X, Li ZY, Zeng L, Zhang AQ, Pan W, Gu W, Jiang JX. Neutrophil CD64 expression as a diagnostic marker for sepsis in adult patients: a meta-analysis. Crit Care. 2015 Jun 10;19(1):245. doi: 10.1186/s13054-015-0972-z.
- Background: PubMed 17108056Matmati M, Pouwels W, van Bruggen R, Jansen M, Hoek RM, Verhoeven AJ, Hamann J. The human EGF-TM7 receptor EMR3 is a marker for mature granulocytes. J Leukoc Biol. 2007 Feb;81(2):440-8. doi: 10.1189/jlb.0406276. Epub 2006 Nov 15.
- Background: PubMed 36592205Povoa P, Coelho L, Dal-Pizzol F, Ferrer R, Huttner A, Conway Morris A, Nobre V, Ramirez P, Rouze A, Salluh J, Singer M, Sweeney DA, Torres A, Waterer G, Kalil AC. How to use biomarkers of infection or sepsis at the bedside: guide to clinicians. Intensive Care Med. 2023 Feb;49(2):142-153. doi: 10.1007/s00134-022-06956-y. Epub 2023 Jan 2.
- Background: PubMed 34599691Evans 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, Moller MH, 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. Intensive Care Med. 2021 Nov;47(11):1181-1247. doi: 10.1007/s00134-021-06506-y. Epub 2021 Oct 2. No abstract available.
- 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.
MA YILEI contact
ZHOU JIANCANG principal investigator
Sir Run Run Shaw Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sepsis, run by Sir Run Run Shaw Hospital at 1 site in China.
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 6 inclusion and 9 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: looking for participants now, as of the sponsor's last update on 28 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
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 ZHOU JIANCANG (+86 13867413145, jiancangzhou@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Diagnostic Accuracy of Neutrophil EMR3 Expression for Sepsis (time frame: At baseline (T0), within 6 hours of enrollment or initial ICU admission.). 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 NCT07896018, which also lists 12 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 28 Oct 2026.