SepsisNEPSISNCT07796386
Plasma Neprilysin for Predicting Sepsis Within 48 Hours in ICU Patients With Infection or Suspected Infection
An observational study of Sepsis and Infection, run by Zhujiang Hospital at 2 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- Plasma Neprilysin Measurement, Conventional Sepsis Biomarker Measurement and Sublingual Microcirculation Assessment
- Type of treatment
- Pill or oral medicine
- How many people
- 488 participants
- Where
- 2 sitesChina
- Study dates
- 1 Aug 2026to 30 Apr 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites
Guangzhou First People's Hospital
Guangzhou, Guangdong, 510180
Wei Fu, vivid911@126.com, vivid911@126.com
Zhi Yang
Department of Critical Care Medicine of Zhujiang Hospital,Southern Medical University
Guangzhou, Guangdong, 510280
Jingjing Yang, +86 020 62782927, jingjingyang@smu.edu.cn
Jingjing Yang, +86 020 62782927
About this study
Official title: Plasma Neprilysin for Early Prediction of Sepsis Within 48 Hours in ICU Patients With Infection or Suspected Infection (NEPSIS): A Multicenter Prospective Cohort Study
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.
Read the 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.
- Being tested
- Plasma Neprilysin Measurement, Conventional Sepsis Biomarker Measurement, Sublingual Microcirculation Assessment
- Keywords
- sepsis, biomarker, prediction, neprilysin
- Medical subject headings
- Sepsis, Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Plasma Neprilysin MeasurementDiagnostic 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.
Conventional Sepsis Biomarker MeasurementDiagnostic test
Plasma will be batch-tested for interleukin-6, C-reactive protein, and procalcitonin for comparison with plasma neprilysin.
Sublingual Microcirculation AssessmentDiagnostic 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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Diagnostic Test: Plasma Neprilysin Measurement; Diagnostic Test: Conventional Sepsis Biomarker Measurement; Diagnostic Test: Sublingual Microcirculation Assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From enrollment through 48 hours
Secondary outcomes (2)
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.
Measured: From enrollment through 48 hours
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.
Measured: From enrollment through 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2026
- Study start1 Aug 2026 (estimated)
- Primary completion31 Dec 2027 (estimated)
- Study completion30 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- More trials run by Zhujiang HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 488 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zhujiang Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Guangzhou First People's Hospital, Guangdong Basic and Applied Basic Science Foundation
- Responsible party
- Principal investigator, Liu Zhanguo, Zhujiang Hospital
- Investigators
- Zhanguo Liu, Principal investigator, Department of Critical Care Medicine of Zhujiang Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07796386
- Sponsor's protocol ID
- 2026-KY-293-01
- Other IDs
- 2025A1515220030
- Acronym
- NEPSIS
- Status last verified
- Aug 2026
- First submitted
- 26 Aug 2026
- Last updated
- 1 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 41159833
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Plasma Neprilysin for Early Prediction of Sepsis Within 48 Hours in ICU Patients With Infection or Suspected Infection (NEPSIS): A Multicenter Prospective Cohort Study
- ClinicalTrials.gov ID
- NCT07796386
- Acronym / sponsor ID
- NEPSIS / 2026-KY-293-01
- Keywords
- sepsis, biomarker, prediction, neprilysin
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 488 participants (estimated)
- Lead sponsor
- Zhujiang HospitalUniversity, hospital or other
- Collaborators
- Guangzhou First People's Hospital, Guangdong Basic and Applied Basic Science Foundation
- Study start
- 1 Aug 2026 (estimated)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 30 Apr 2028 (estimated)
- First posted
- 1 Sep 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ICU Participants With Infection or Suspected Infection | – | Diagnostic Test: Plasma Neprilysin Measurement, Diagnostic Test: Conventional Sepsis Biomarker Measurement, Diagnostic Test: Sublingual Microcirculation AssessmentAdults 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Plasma Neprilysin MeasurementPlasma 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 test | ICU Participants With Infection or Suspected Infection |
| Conventional Sepsis Biomarker MeasurementPlasma will be batch-tested for interleukin-6, C-reactive protein, and procalcitonin for comparison with plasma neprilysin. | Diagnostic test | ICU Participants With Infection or Suspected Infection |
| Sublingual Microcirculation AssessmentSublingual 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. | Diagnostic test | ICU Participants With Infection or Suspected Infection |
Primary outcome
Development of sepsis within 48 hours
Time frame: 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.
2 secondary outcomes
Predictive Performance of Plasma Neprilysin Combined With Sublingual Microcirculation Measures for Sepsis Within 48 Hours
Time frame: From enrollment through 48 hours
Comparative Predictive Performance of Plasma Neprilysin and Conventional Biomarkers for Sepsis Within 48 Hours
Time frame: From enrollment through 48 hours
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2026.
- Results publication: PubMed 41159833Ranzani 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Zhanguo Liu principal investigator
Department of Critical Care Medicine of Zhujiang Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sepsis and Infection, run by Zhujiang Hospital at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 1 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Zhanguo Liu (+86 020 62782927, zhguoliu@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Development of sepsis within 48 hours (time frame: From enrollment through 48 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07796386, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2026.