Evaluating the Accuracy of Multiple Blood Tests to Diagnose Sepsis in Adult Burn Patients (BioBurnSepsis)

Dohern Kym

Status: Not yet enrolling

Conditions: Sepsis - to Reduce Mortality in the Intensive Care Unit; Burns Involving 20% or More of Body Surface

Study type: Observational

Funder types: Other

Identifiers

NCT07126574

2025-020

Details and patient eligibility

About

This prospective diagnostic accuracy study evaluates the performance of presepsin and C-reactive protein (CRP) as early biomarkers for suspected sepsis in adult burn patients. From January 2021 to December 2022, 370 patients with ≥20% total body surface area burns admitted to the Burn Intensive Care Unit at Hallym University Hangang Sacred Heart Hospital were screened; 221 met inclusion criteria. At each clinical suspicion of sepsis (≥2 SIRS criteria), venous blood was drawn for simultaneous measurement of presepsin (via chemiluminescent immunoassay) and CRP (via immunoturbidimetric assay). Diagnostic accuracy will be quantified by sensitivity, specificity, positive/negative predictive values, and area under the ROC curve. The goal is to determine whether presepsin outperforms CRP for early sepsis detection in severe burn patients.

Full description

Background and Rationale Sepsis is a leading cause of mortality in patients with severe burns, yet its early diagnosis is challenging. The systemic inflammatory response triggered by the burn injury itself often mimics the clinical signs of sepsis, confounding diagnosis and leading to delayed or unnecessary antibiotic use. Conventional biomarkers like C-reactive protein (CRP) and procalcitonin (PCT) lack specificity in this population, as they are elevated by the sterile inflammation from the burn itself. This study aims to overcome these limitations by evaluating the diagnostic utility of a multi-biomarker panel, analyzing their dynamic changes over time, and leveraging machine learning to develop a more accurate and interpretable diagnostic model for sepsis in burn patients.

Study Design and Objectives This is a single-center, prospective observational cohort study conducted at the Burn Intensive Care Unit (BICU) of Hallym University Hangang Sacred Heart Hospital. The study will run from September 2025 to August 2026.

Primary Objective: To evaluate the diagnostic accuracy (sensitivity, specificity, AUC) of a multi-biomarker panel-comprising Serum Amyloid A (SAA), Procalcitonin (PCT), Presepsin (PSP), and CRP-for diagnosing sepsis in adult burn patients, using the Sepsis-3 criteria as the reference standard.

Secondary Objectives: To compare the diagnostic performance of the multi-biomarker panel against individual biomarkers and standard clinical severity scores (e.g., SOFA score).

To assess the panel's ability to predict disease severity and mortality (28-day and 90-day).

To develop a predictive model for sepsis using machine learning and interpret the model's decisions using SHAP (SHapley Additive exPlanations) analysis.

Methods and Analysis Data and Sample Collection: For enrolled patients, comprehensive clinical data-including demographics, burn characteristics (%TBSA, inhalation injury), severity scores (SOFA, APACHE II), and microbiological results-will be collected. Blood samples for biomarker analysis will be collected upon ICU admission (baseline), at the time of clinical suspicion of sepsis, and serially thereafter (daily if possible) for a minimum of seven days to capture the temporal dynamics of the biomarkers.

Biomarker Panel: The core panel includes SAA, PCT, PSP, and CRP, supplemented by routine hematological markers like WBC, platelet count, NLR, and PLR.

Statistical and Advanced Analytical Plan:

Diagnostic Accuracy: Traditional statistical methods, including ROC curve analysis and DeLong's test, will be used to compare the diagnostic performance of individual and combined biomarkers.

Dynamic Analysis: To analyze the longitudinal biomarker data, generalized estimating equations (GEE) or linear mixed models (LMM) will be employed. This will allow for the quantitative assessment of biomarker trends (e.g., rate of change) and their association with sepsis diagnosis and prognosis.

Machine Learning and Interpretation: A key component of this study is the development of advanced predictive models using machine learning algorithms (e.g., Random Forest, XGBoost). To address the "black box" nature of these models, we will utilize SHAP analysis to provide transparent interpretations. This will quantify the precise contribution of each biomarker to individual patient predictions, offering deeper clinical insights into the pathophysiological state.

Sample Size: A total of 165 patients will be recruited. This sample size was calculated using G*Power software to achieve 80% power at a significance level of 0.05, assuming an expected sensitivity of 90% and specificity of 80% for the multi-biomarker panel in ROC analysis.

Enrollment: 165 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age 18 years or older.
• Admission to the Burn Intensive Care Unit (BICU) with a burn injury covering ≥10% of the Total Body Surface Area (TBSA).
• Undergoing a blood culture due to clinical suspicion of sepsis (e.g., fever, abnormal white blood cell count, hemodynamic instability) during the ICU stay.
• The participant or their legally authorized representative has provided written informed consent.

Exclusion criteria

• Pregnancy.
• Pre-existing immunological conditions that, in the investigator's judgment, could interfere with biomarker interpretation (e.g., long-term use of immunosuppressants, congenital immunodeficiency).
• Inability to participate at the time of study-related blood collection due to initial emergency surgery, major trauma, or significant hemorrhage.
• Any other condition for which the principal investigator deems participation to be inappropriate or unsafe for the patient.

Trial design

165 participants in 1 patient group

Burn patients with suspected sepsis

Description:

Adults ≥18 years with ≥20% TBSA burns admitted to the Burn Intensive Care Unit who developed clinically suspected sepsis (≥2 SIRS criteria)