Plasma Neprilysin for Predicting Sepsis Within 48 Hours in ICU Patients With Infection or Suspected Infection

NCT07796386 | Not Yet Recruiting

• 2 other identifiers: 2026-KY-293-012025A1515220030
• Study Type: observational
• Target: 488
• Locations: 1 country
• Sites: 2

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.

Conditions

Sepsis; Infection

Keywords

sepsis; biomarker; prediction; neprilysin

Outcome Measures

Primary Outcomes (1)

• 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.

  From enrollment through 48 hours

Secondary Outcomes (2)

• Predictive Performance of Plasma Neprilysin Combined With Sublingual Microcirculation Measures for Sepsis Within 48 Hours

  From enrollment through 48 hours

• Comparative Predictive Performance of Plasma Neprilysin and Conventional Biomarkers for Sepsis Within 48 Hours

  From enrollment through 48 hours

Other Outcomes (1)

• All-Cause Mortality Within 28 Days

  From enrollment through Day 28

Study Arms (1)

ICU Participants With Infection or Suspected Infection

Adults admitted to the intensive care unit with confirmed or suspected infection who do not meet the protocol-defined criteria for sepsis at enrollment. Participants will be observed for the development of sepsis through 48 hours and followed for survival through Day 28.

Diagnostic Test: Plasma Neprilysin Measurement; Diagnostic Test: Conventional Sepsis Biomarker Measurement; Diagnostic Test: Sublingual Microcirculation Assessment

Interventions

Plasma Neprilysin Measurement DIAGNOSTIC_TEST

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.

ICU Participants With Infection or Suspected Infection

Conventional Sepsis Biomarker Measurement DIAGNOSTIC_TEST

Plasma will be batch-tested for interleukin-6, C-reactive protein, and procalcitonin for comparison with plasma neprilysin.

ICU Participants With Infection or Suspected Infection

Sublingual Microcirculation Assessment DIAGNOSTIC_TEST

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.

ICU Participants With Infection or Suspected Infection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Zhujiang Hospital: lead
• Guangzhou First People's Hospital: collaborator
• Guangdong Basic and Applied Basic Science Foundation: collaborator

Study Sites (2)

Guangzhou First People's Hospital

Guangzhou, Guangdong, 510180, China

Location

Department of Critical Care Medicine of Zhujiang Hospital,Southern Medical University

Guangzhou, Guangdong, 510280, China

Location

Related Publications (1)

• Ranzani OT, Singer M, Salluh JIF, Shankar-Hari M, Pilcher D, Berger-Estilita J, Coopersmith CM, Juffermans NP, Laffey J, Reinikainen M, Neto AS, Tavares M, Timsit JF, Arias Lopez MDP, Arulkumaran N, Aryal D, Azoulay E, Celi LA, Chaudhuri D, De Lange D, De Waele J, Dos Santos CC, Du B, Einav S, Engelbrecht T, Fazla F, Ferrer R, Finazzi S, Fujii T, Gershengorn HB, Greene JD, Haniffa R, Hao S, Hasan MS, Hollenberg S, Ippolito M, Jung C, Kirov M, Kobari S, Lakbar I, Lipman J, Liu V, Liu X, Lobo SM, Magatti D, Martin GS, Metnitz B, Metnitz P, Myatra SN, Oczkowski S, Paiva JA, Paruk F, Pekkarinen PT, Piquilloud L, Polkki A, Prescott HC, Blaser AR, Rezende E, Robba C, Rochwerg B, Ruckly S, Samei R, Schenck EJ, Secombe P, Sendagire C, Siaw-Frimpong M, Simpkin AJ, Soares M, Summers C, Szczeklik W, Takala J, Tanaka S, Tricella G, Vincent JL, Wendon J, Zampieri FG, Rhodes A, Moreno R. Development and Validation of the Sequential Organ Failure Assessment (SOFA)-2 Score. JAMA. 2025 Dec 16;334(23):2090-2103. doi: 10.1001/jama.2025.20516.

  PMID: 41159833 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

plasma

MeSH Terms

Conditions

Sepsis; Infections

Condition Hierarchy (Ancestors)

Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Zhanguo Liu

  Department of Critical Care Medicine of Zhujiang Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhanguo Liu

CONTACT

+86 020 62782927; zhguoliu@163.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 26, 2026
• First Posted: September 1, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): April 30, 2028
• Last Updated: September 1, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)