Infection, Sepsis
Conditions
Keywords
sepsis, biomarker, prediction, neprilysin
Brief summary
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.
Detailed description
This is a multicenter prospective observational cohort study conducted in the intensive care units of Zhujiang Hospital, Southern Medical University, and Guangzhou First Municipal People's Hospital. Newly admitted intensive care unit participants will be screened daily according to predefined eligibility criteria. Eligible participants with confirmed or suspected infection who do not meet the protocol-defined criteria for sepsis at enrollment will be approached consecutively. Written informed consent will be obtained from the participant or the participant's legally authorized representative before enrollment. Day 0 is defined as the date of the first plasma sample collection. Plasma samples will be collected on Day 0 and Day 1, processed according to standardized procedures, aliquoted, stored at -80 degrees Celsius, and batch-tested for neprilysin, interleukin-6, C-reactive protein, and procalcitonin. Laboratory personnel will be blinded to clinical outcomes. When oral conditions permit, sublingual microcirculation will be assessed on Day 0 and Day 1. Measurements will include microvascular flow index, perfused vessel density, and perfused boundary region. Image assessors will be blinded to clinical outcomes. Sequential Organ Failure Assessment 2 scores will be evaluated at baseline, Day 1, and Day 2. Development of sepsis within 48 hours will be independently adjudicated by two investigators who are blinded to plasma neprilysin and sublingual microcirculation results. Disagreements will be resolved by a senior intensive care physician. Receiver operating characteristic curve analysis and logistic regression will be used to evaluate plasma neprilysin alone and in combination with conventional biomarkers and sublingual microcirculation measurements. Predictive performance will be internally validated using bootstrap resampling.
Interventions
DIAGNOSTIC_TESTPlasma Neprilysin Measurement
Plasma collected at enrollment will be tested for neprilysin using an enzyme-linked immunosorbent assay. The result will not be used to guide clinical treatment.
DIAGNOSTIC_TESTConventional Sepsis Biomarker Measurement
Plasma will be batch-tested for interleukin-6, C-reactive protein, and procalcitonin for comparison with plasma neprilysin.
DIAGNOSTIC_TESTSublingual Microcirculation Assessment
Sublingual 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.
Sponsors
Zhujiang Hospital
Guangzhou First People's Hospital
Guangdong Basic and Applied Basic Science Foundation
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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. * Written informed consent provided by the participant or the participant's legally authorized representative.
Exclusion criteria
* 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. * Considered unsuitable for participation by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Development of sepsis within 48 hours | From enrollment through 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
| Measure | Time frame | Description |
|---|---|---|
| Predictive Performance of Plasma Neprilysin Combined With Sublingual Microcirculation Measures for Sepsis Within 48 Hours | From enrollment through 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 | From enrollment through 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. |
Countries
China
Contacts
CONTACTZhanguo Liu
PRINCIPAL_INVESTIGATORZhanguo Liu
Department of Critical Care Medicine of Zhujiang Hospital
Outcome results
None listed