PRIME Sepsis Trial: Early Sepsis Detection in the Emergency Department Using Presepsin and Immature Granulocytes

September 10, 2026 updated by: Chang Gung Memorial Hospital

PRIME-Sepsis Trial: Presepsin and Immature Granulocytes for Multicenter Early Sepsis Detection in the Emergency Department: A Prospective Observational Study

Early identification and timely intervention for sepsis in the emergency department (ED) are critical for improving patient outcomes. However, clinical diagnosis remains challenging due to the non-specific nature of early systemic symptoms. This study protocol aims to evaluate the diagnostic accuracy of a combined approach using Immature Granulocytes (IG) and Presepsin (sCD14-ST) for the early detection of sepsis in undifferentiated ED patients.

Study Overview

Status

Not yet recruiting

Conditions

Detailed Description

Sepsis is characterized by a dysregulated host inflammatory response to infection, potentially leading to multiple organ dysfunction syndrome (MODS) and death. Globally, the estimated annual incidence of sepsis ranges from 18 to 31.5 million cases, with mortality rates as high as 30%. Approximately 70% of sepsis patients are initially managed in the emergency department (ED). Although delayed recognition and treatment are associated with poorer outcomes, and early evidence-based intervention significantly improves survival , early identification of sepsis in the ED remains a formidable clinical challenge . Despite the critical need for prompt intervention, research indicates that the detection of infection is often delayed by more than 4 hours after hospital admission and by over 8 hours in approximately 30% of ED cases.

Diverse biomarkers have been proposed to facilitate timely diagnosis, risk stratification, and the initiation of appropriate treatment. Complete blood count (CBC) parameters are particularly advantageous in the ED due to their rapid turnaround time, low cost, and repeatability. Traditionally, white blood cell (WBC) count and immature granulocyte (IG) count have served as first-line indicators. Advanced hematology technologies now provide detailed morphologic data (e.g., cell volume and structural changes), potentially enhancing the diagnostic value of these parameters. While IG has been recognized as a marker of systemic inflammation and sepsis, its clinical utility remains a subject of ongoing debate. Specifically, some studies suggest limited predictive value for long-term outcomes such as 28-day mortality, leading to inconsistent conclusions regarding its diagnostic reliability when used in isolation for the detection of sepsis.

Recent investigations into IG for ED sepsis diagnosis have reported areas under the receiver operating characteristic curve (AUC) ranging from 0.52 to 0.93. This pronounced variability is likely attributable to differences in study methodologies and patient populations. Concurrently, Presepsin (soluble CD14 subtype, sCD14-ST) has emerged as a promising alternative biomarker. Presepsin is generated via monocyte activation and pathogen phagocytosis, resulting in a rapid surge in circulating levels during the incipient immune response. Evidence suggests that Presepsin rises earlier than conventional biomarkers and correlates strongly with sepsis severity and clinical outcomes. Specifically, Presepsin has demonstrated superior or comparable diagnostic performance to C-reactive protein (CRP) and procalcitonin (PCT) in emergency settings.

Previous investigations have consistently demonstrated the superior diagnostic performance of Presepsin, with reported Area Under the Receiver Operating Characteristic curve (AUROC) values often exceeding 0.90 in both emergency sepsis presentations and complex postoperative infectious settings, supporting its role as a benchmark biomarker for early infection detection.

In the PRIME-Sepsis Trial (Presepsin and Immature Granulocytes for Multicenter Early Sepsis Detection), we aim to evaluate the synergistic diagnostic accuracy of integrating IG and Presepsin for identifying sepsis in adult patients with a high clinical suspicion of infection in the ED. While Presepsin offers superior diagnostic potential in the hyper-acute phase, IG provides a readily available, cost-effective reflection of the systemic hematopoietic response. By synergizing these complementary biomarkers, our primary objective is to assess the incremental diagnostic yield of a combined molecular-cellular model against multiple reference standards (Sepsis-2, Sepsis-3, and qSOFA). This approach will enable us to derive and evaluate a novel dual-parameter diagnostic algorithm, ultimately facilitating earlier clinical decision-making and improving prognostic accuracy in diverse emergency care settings. This prospective, multicenter design minimizes the biases inherent in previous retrospective analyses, providing a more robust foundation for clinical implementation.

Study Type

Observational

Enrollment (Estimated)

699

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Chen June Seak, M.D
Phone Number: +886-975-365-802
Email: julianseak@hotmail.com

Study Locations

Taiwan
- - New Taipei City, Taiwan, 23652
    - Department of Emergency Medicine, New Taipei Municipal Tucheng Hospital
    - Contact:
      
      Chen June Seak
      
      Phone Number: +886-975-365-802
      
      Email: julianseak@hotmail.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

Adult
Older Adult

Accepts Healthy Volunteers

Sampling Method

Non-Probability Sample

Study Population

The study population consists of adult patients (aged 18 years and older) who present to the emergency department of participating multi-center medical institutions with a suspected or confirmed infection and exhibit clinical signs suggestive of early sepsis.

Description

Inclusion Criteria:

Age: Adult patients (≥ 18 years old) presenting to the EDs of the participating sites.
Clinical Suspicion of Infection: A high clinical suspicion of infection as determined by the attending emergency physician, accompanied by either a Systemic Inflammatory Response Syndrome (SIRS) score ≥ 2 or a Quick Sequential Organ Failure Assessment (qSOFA) score ≥ 2.
Rationale: This dual-criteria strategy (SIRS or qSOFA) reflects a pragmatic, high-sensitivity approach designed to capture the full spectrum of sepsis in the emergency setting, overcoming the sensitivity limitations of using a single scoring system.
Feasibility of Biomarker Collection: Ability to obtain blood samples for IG and Presepsin measurement within 2 hours of ED arrival.
Informed Consent: Provision of written informed consent obtained from the patient or their legally authorized representative (LAR).

Exclusion Criteria:

Severe Immunosuppression: Active chemotherapy, history of organ transplantation, or long-term high-dose corticosteroid therapy that may confound leukocyte kinetics or suppress systemic inflammatory responses.
Hematological Conditions: Documented hematological malignancies or myelodysplastic syndromes (MDS) capable of altering baseline IG profiles.
Pregnancy or lactation, due to the potential for pregnancy-induced physiological and immunological variability.
Prolonged Prior Hospitalization: Patients transferred from another facility after an admission of >24 hours, as extensive prior intervention may obscure the hyper-acute biomarker kinetics critical for early diagnosis.
Consent Issues: Refusal to provide informed consent by the patient or their LAR.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Number of groups / cohorts

Cohorts and Interventions

Group / Cohort
Suspected Sepsis Cohort This is a purely observational study. Peripheral blood samples are collected at enrollment (T0) solely for the laboratory measurement of Presepsin and immature granulocytes (IG). This process does not alter, delay, or interfere with standard clinical diagnosis, management, or treatment decisions in the emergency department.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic Accuracy of Presepsin for Early Sepsis Screening Time Frame: At enrollment (Time 0 / Emergency Department presentation)	The diagnostic performance of Presepsin (measured in pg/mL) will be evaluated using the Area Under the Receiver Operating Characteristic curve (AUROC). The AUROC will be analyzed to evaluate the ability of Presepsin to differentiate patients with sepsis from those with non-infectious systemic inflammatory response syndrome (SIRS).	At enrollment (Time 0 / Emergency Department presentation)
Diagnostic Accuracy of Immature Granulocytes for Early Sepsis Screening Time Frame: At enrollment (Time 0 / Emergency Department presentation)	The diagnostic performance of immature granulocytes (IG, measured in percentage) will be evaluated using the Area Under the Receiver Operating Characteristic curve (AUROC). The AUROC will be analyzed to evaluate the ability of IG to differentiate patients with sepsis from those with non-infectious systemic inflammatory response syndrome (SIRS).	At enrollment (Time 0 / Emergency Department presentation)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prognostic Value of Presepsin for Predicting Septic Shock Development Time Frame: Through 30 days after enrollment	Evaluation of the capability of Presepsin (measured in pg/mL) to predict progression from early sepsis to septic shock. The prognostic performance will be analyzed by calculating the AUROC, sensitivity, specificity, positive predictive value, and negative predictive value.	Through 30 days after enrollment
Prognostic Value of Immature Granulocytes for Predicting Septic Shock Development Time Frame: Through 30 days after enrollment	Evaluation of the capability of immature granulocytes (IG, measured in percentage) to predict progression from early sepsis to septic shock. The prognostic performance will be analyzed by calculating the AUROC, sensitivity, specificity, positive predictive value, and negative predictive value.	Through 30 days after enrollment
Association Between Initial Presepsin Levels and 30-Day All-Cause Mortality Time Frame: 30 days post-enrollment	The correlation and association between initial Presepsin concentration (measured in pg/mL at emergency department presentation) and 30-day all-cause mortality will be analyzed. The prognostic performance will be evaluated by calculating the Area Under the Receiver Operating Characteristic curve (AUROC) and the Odds Ratio (OR) derived from multiple logistic regression analysis to determine the predictive capability of Presepsin for 30-day mortality.	30 days post-enrollment
Association Between Initial Immature Granulocytes and 30-Day All-Cause Mortality Time Frame: 30 days post-enrollment	The correlation and association between initial immature granulocytes (IG, measured in percentage at emergency department presentation) and 30-day all-cause mortality will be analyzed. The prognostic performance will be evaluated by calculating the Area Under the Receiver Operating Characteristic curve (AUROC) and the Odds Ratio (OR) derived from multiple logistic regression analysis to determine the predictive capability of IG for 30-day mortality.	30 days post-enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chang Gung Memorial Hospital

Investigators

Study Chair: Chi Jui Lin, Department of Medical Laboratory, New Taipei Municipal Tucheng Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

October 1, 2026

Primary Completion (Estimated)

October 1, 2028

Study Completion (Estimated)

April 1, 2029

Study Registration Dates

First Submitted

May 31, 2026

First Submitted That Met QC Criteria

September 10, 2026

First Posted (Actual)

September 16, 2026

Study Record Updates

Last Update Posted (Actual)