About this trial
The goal of this multicenter prospective observational cohort study is to determine whether plasma neprilysin can predict the development of sepsis within 48 hours in adults admitted to an intensive care unit with confirmed or suspected infection who do not have sepsis at enrollment.
The study will be conducted at Zhujiang Hospital, Southern Medical University, and Guangzhou First Municipal People's Hospital. Plasma samples remaining after routine clinical testing will be used to measure neprilysin and conventional sepsis biomarkers. Sublingual microcirculation will also be assessed when feasible.
Participants will be assessed for the development of sepsis from enrollment through 48 hours and will be followed for survival through Day 28. No treatment or clinical intervention will be assigned by the study protocol.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age 18 years or older.
Confirmed or suspected infection as assessed by the treating physician based on symptoms, signs, laboratory findings, imaging findings, microbiological findings, or evidence of an infection source, with systemic antimicrobial therapy initiated or planned.
Does not meet the protocol-defined criteria for sepsis at enrollment. In the setting of confirmed or suspected infection, there must be no acute increase of 2 or more points in the Sequential Organ Failure Assessment 2 score from baseline that is attributable to infection.
Expected by the treating physician to remain in the intensive care unit for more than 48 hours after enrollment.
Disqualifiers
Sepsis diagnosed at intensive care unit admission or fulfillment of the Sepsis-3 criteria at screening.
Insufficient clinical data to determine the baseline SOFA-2 score according to the prespecified assessment criteria.
Patients with limited nursing care (patients for whom active treatment has been withdrawn)
No blood sample is available on the day of enrollment.
Trial population
Adult critically ill participants admitted to the intensive care unit of Zhujiang Hospital, Southern Medical University, with confirmed or suspected infection who do not meet the protocol-defined criteria for sepsis at enrollment. Newly admitted intensive care unit participants will be screened daily.
Trial design
Cohort
Prospective
Treatments tested in this trial
Plasma Neprilysin Measurement
Diagnostic testPlasma collected at enrollment will be tested for neprilysin using an enzyme-linked immunosorbent assay. The result will not be used to guide clinical treatment.
Conventional Sepsis Biomarker Measurement
Diagnostic testPlasma will be batch-tested for interleukin-6, C-reactive protein, and procalcitonin for comparison with plasma neprilysin.
Sublingual Microcirculation Assessment
Diagnostic testSublingual microcirculation will be assessed when oral conditions permit. Measurements will include microvascular flow index, perfused vessel density, and perfused boundary region. The results will not be used to assign treatment.
Treatment groups
Trial outcomes
Primary outcomes
Development of sepsis within 48 hours
The reference outcome is the development of sepsis within 48 hours after enrollment. Sepsis is defined as confirmed or suspected infection with an acute increase of at least 2 points in the Sequential Organ Failure Assessment 2 score from baseline that is attributable to infection. The predictive performance of baseline plasma neprilysin will be summarized using the area under the receiver operating characteristic curve with its 95 percent confidence interval. Sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratios will also be reported at the selected cutoff value.
Secondary outcomes
Predictive Performance of Plasma Neprilysin Combined With Sublingual Microcirculation Measures for Sepsis Within 48 Hours
A prediction model combining baseline plasma neprilysin, microvascular flow index, perfused vessel density, and perfused boundary region will be evaluated. Model performance will be summarized using the area under the receiver operating characteristic curve with its 95 percent confidence interval and measures of calibration.
Comparative Predictive Performance of Plasma Neprilysin and Conventional Biomarkers for Sepsis Within 48 Hours
The predictive performance of baseline plasma neprilysin will be compared with that of interleukin-6, C-reactive protein, and procalcitonin. Areas under the receiver operating characteristic curves will be calculated with 95 percent confidence intervals and compared using the DeLong method.
Other outcomes
All-Cause Mortality Within 28 Days
Vital status will be determined using hospital records or telephone follow-up.
Sponsors and contacts
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Zhujiang Hospital
Lead sponsor
Guangzhou First People's Hospital
Collaborator
Guangdong Basic and Applied Basic Science Foundation
Collaborator
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