Late-Onset Neonatal SepsisEMERAUDENCT03299751
Evaluation of bioMarkErs to Reduce Antibiotics Use in hospitalizeD nEonates
A study testing Diagnostic performances of biomarkers combination in people with Late-Onset Neonatal Sepsis, run by Hospices Civils de Lyon at 2 sites in France.
Trial summary
Late-onset neonatal sepsis (LOS), occurring in newborn of at least 7 days of life, is frequently observed in Neonatal Intensive Care Units (NICUs) and potentially severe (mortality, neurologic and respiratory impairments). Despite its high prevalence, a reliable diagnostic remains difficult. Read more about this study
- Who is it for?
- Ages 7 days and older
- Conditions the study is for
- Late-Onset Neonatal Sepsis
- What is being tested?
- Diagnostic performances of biomarkers combination
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 233 participants
- Where
- 2 sitesFrance
- Study dates
- 22 Nov 2017to 20 Nov 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 7 days and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- patients hospitalized in NICU;
- patients with suggestive signs of LOS including at least one of the following:
- o Fever > 38°C; tachycardia > 160bpm160 bpm; capillary refill time > 3 seconds; grey and/or pale skin complexion; apnea/ bradycardia syndrome,; bloating; rectal bleeding; hypotonia; lethargy; seizures without other obvious cause; increased ventilatory support and/or increased FiO2; cutaneous rash; inflammation at the needle-puncture site of the central venous catheter;
- patients with a standard of care blood sampling, including at least a blood culture;
- consent form signed by at least one parent/ legal representative.
Who cannot join
- patients treated with antibiotics for a bacteriologically confirmed infection at the moment of/ or 48 hours before blood sampling
- patients who underwent surgery during the 7 days prior to inclusion
- patients vaccinated during the 7 days prior to inclusion
Trial locations and contacts
2 sites in 1 country.
About this study
Official title: Evaluation of Biomarkers Combination Performance for the Diagnosis of Neonatal Sepsis in NICU Hospitalized Newborns
Late-onset neonatal sepsis (LOS), occurring in newborn of at least 7 days of life, is frequently observed in Neonatal Intensive Care Units (NICUs) and potentially severe (mortality, neurologic and respiratory impairments).
Despite its high prevalence, a reliable diagnostic remains difficult. Currently, nonspecific clinical signs that might be linked to other neonatal conditions, such as prematurity and birth defects are used to determine the diagnosis of LOS. Laboratory results of biological markers, such as C-Reactive Protein (CRP) and Procalcitonin (PCT) are often delayed in comparison with LOS onset. Blood culture results are too late and lack sensitivity.
Read more
Excessive antibiotic use is observed in a large proportion of NICU hospitalized newborns. This results in an increased antibiotic resistance, microbiota modification, neonatal complications (pulmonary, ophthalmologic and neurologic) and mortality.
The primary objective is to identify, on a cohort of 250 patients, the optimal biomarker combination with good diagnostic performance (i.e. with maximal Area Under the ROC Curve) to early exclude a LOS diagnostic in newborns of at least 7 days of life with suggestive signs.
This identification will be carried out, as a secondary objective, with a sub-group of pre-term neonates whose birth weight is less than 1500 grams. The diagnostic value of the clinical signs that are suggestive of LOS will also be determined (sensitivity, specificity, negative and positive predictive values).
Once identified, the biomarker combination is expected to reduce unjustified antibiotic use.
- Conditions
- Late-Onset Neonatal Sepsis
- Being tested
- Diagnostic performances of biomarkers combination
- Keywords
- neonatal sepsis, biomarker combination, diagnostic, antibiotic use, newborn, preterm neonates, NICU
- Medical subject headings
- Neonatal Sepsis, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Diagnostic performances of biomarkers combinationBiological
A blood sample of 400µL will be drawn at inclusion, when neonatal sepsis is suspected, at the same time of a venipuncture prescribed for standard care.
The dosage of 11 biomarkers will be performed in a central laboratory. The adjudication committee composed with 3 neonatalogists will classify patients in 3 groups (infected, not infected or unclassified patients), based on their clinical and biological data obtained, through the standard of care practice, during the 48 hours following inclusion. The adjudication committee will be blinded to the biomarkers results.
The adjudication committee composed with 3 neonatalogists will classify patients in 3 groups (infected, not infected or unclassified patientsconfirmed infection, refuted infection), based on their clinical and biological data obtained, through the standard of care practice, during the 48 hours following inclusion. The adjudication committee will be blinded to the biomarkers results.
| Study group | Role | What they receive |
|---|---|---|
| NICU newborns of at least 7 days of life with suggestive signs | Experimental | Not described Receives: Biological: Diagnostic performances of biomarkers combination |
What is being measured
The primary outcome is the main question the study is designed to answer.
LOS diagnosis in NICU newborns of at least 7 days of life with suggestive clinical signs, confirmed by adjudication committee
The primary outcome measure will be determined by an independent adjudication committee that will classify the patients into the following categories: infected, not infected or unclassified patients. This committee will be blinded to the biomarkers that will be used to identify a combination with the best negative predictive value. It will be composed of two neonatologists and a pediatrician specialized in the child infectious diseases.
The diagnostic performance of the biomarkers combination will be based on the adjudication committee
Measured: hour 48
Secondary outcomes (1)
LOS diagnosis in NICU preterm neonates, whose weight at birth is less than 1500 grams, of at least 7 days of life, with suggestive clinical signs, confirmed by adjudication committee.
The primary outcome measure will be determined by an independent adjudication committee that will classify the patients into the following categories: infected, not infected or unclassified patients. This committee will be blinded to the biomarkers that will be used to identify a combination with the best negative predictive value. It will be composed of two neonatologists and a pediatrician specialized in the child infectious diseases.
The diagnostic performance of the biomarkers combination will be based on the adjudication committee classification (gold standard).
Measured: Hour 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2017
- Study start22 Nov 2017
- Primary completion20 Nov 2020
- Study completion20 Nov 2020
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 Late-Onset Neonatal SepsisStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 233 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03299751
- Sponsor's protocol ID
- 69HCL17_0492
- Acronym
- EMERAUDE
- Status last verified
- Aug 2025
- First submitted
- 28 Sep 2017
- Last updated
- 4 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Pons S, Trouillet-Assant S, Subtil F, Abbas-Chorfa F, Cornaton E, Berthiot A, Galletti S, Plat A, Rapin S, Trapes L, Generenaz L, Brengel-Pesce K, Callies A, Plaisant F, Claris O, Portefaix A, Flamant C, Butin M. Performance of 11 Host Biomarkers Alone or in Combination in the Diagnosis of Late-Onset Sepsis in Hospitalized Neonates: The Prospective EMERAUDE Study. Biomedicines. 2023 Jun 13;11(6):1703. doi: 10.3390/biomedicines11061703.
PubMed 37371798
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Biomarkers Combination Performance for the Diagnosis of Neonatal Sepsis in NICU Hospitalized Newborns
- ClinicalTrials.gov ID
- NCT03299751
- Acronym / sponsor ID
- EMERAUDE / 69HCL17_0492
- Conditions
- Late-Onset Neonatal Sepsis
- Keywords
- neonatal sepsis, biomarker combination, diagnostic, antibiotic use, newborn, preterm neonates, NICU
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 233 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 22 Nov 2017 (actual)
- Primary completion
- 20 Nov 2020 (actual)
- Study completion
- 20 Nov 2020 (actual)
- First posted
- 3 Oct 2017 (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.
Late-onset neonatal sepsis (LOS), occurring in newborn of at least 7 days of life, is frequently observed in Neonatal Intensive Care Units (NICUs) and potentially severe (mortality, neurologic and respiratory impairments).
Despite its high prevalence, a reliable diagnostic remains difficult. Currently, nonspecific clinical signs that might be linked to other neonatal conditions, such as prematurity and birth defects are used to determine the diagnosis of LOS. Laboratory results of biological markers, such as C-Reactive Protein (CRP) and Procalcitonin (PCT) are often delayed in comparison with LOS onset. Blood culture results are too late and lack sensitivity.
Excessive antibiotic use is observed in a large proportion of NICU hospitalized newborns. This results in an increased antibiotic resistance, microbiota modification, neonatal complications (pulmonary, ophthalmologic and neurologic) and mortality.
The primary objective is to identify, on a cohort of 250 patients, the optimal biomarker combination with good diagnostic performance (i.e. with maximal Area Under the ROC Curve) to early exclude a LOS diagnostic in newborns of at least 7 days of life with suggestive signs.
This identification will be carried out, as a secondary objective, with a sub-group of pre-term neonates whose birth weight is less than 1500 grams. The diagnostic value of the clinical signs that are suggestive of LOS will also be determined (sensitivity, specificity, negative and positive predictive values).
Once identified, the biomarker combination is expected to reduce unjustified antibiotic use.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NICU newborns of at least 7 days of life with suggestive signs | Experimental | Biological: Diagnostic performances of biomarkers combination |
Who may qualify
- Ages
- 7 days and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- patients hospitalized in NICU;
- patients with suggestive signs of LOS including at least one of the following:
- o Fever > 38°C; tachycardia > 160bpm160 bpm; capillary refill time > 3 seconds; grey and/or pale skin complexion; apnea/ bradycardia syndrome,; bloating; rectal bleeding; hypotonia; lethargy; seizures without other obvious cause; increased ventilatory support and/or increased FiO2; cutaneous rash; inflammation at the needle-puncture site of the central venous catheter;
- patients with a standard of care blood sampling, including at least a blood culture;
- consent form signed by at least one parent/ legal representative.
Key exclusion criteria (3 listed)
- patients treated with antibiotics for a bacteriologically confirmed infection at the moment of/ or 48 hours before blood sampling
- patients who underwent surgery during the 7 days prior to inclusion
- patients vaccinated during the 7 days prior to inclusion
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 |
|---|---|---|
| Diagnostic performances of biomarkers combinationA blood sample of 400µL will be drawn at inclusion, when neonatal sepsis is suspected, at the same time of a venipuncture prescribed for standard care. The dosage of 11 biomarkers will be performed in a central laboratory. The adjudication committee composed with 3 neonatalogists will classify patients in 3 groups (infected, not infected or unclassified patients), based on their clinical and biological data obtained, through the standard of care practice, during the 48 hours following inclusion. The adjudication committee will be blinded to the biomarkers results. The adjudication committee composed with 3 neonatalogists will classify patients in 3 groups (infected, not infected or unclassified patientsconfirmed infection, refuted infection), based on their clinical and biological data obtained, through the standard of care practice, during the 48 hours following inclusion. The adjudication committee will be blinded to the biomarkers results. | Biological | NICU newborns of at least 7 days of life with suggestive signs |
Primary outcome
LOS diagnosis in NICU newborns of at least 7 days of life with suggestive clinical signs, confirmed by adjudication committee
Time frame: hour 48
The primary outcome measure will be determined by an independent adjudication committee that will classify the patients into the following categories: infected, not infected or unclassified patients. This committee will be blinded to the biomarkers that will be used to identify a combination with the best negative predictive value. It will be composed of two neonatologists and a pediatrician specialized in the child infectious diseases. The diagnostic performance of the biomarkers combination will be based on the adjudication committee
1 secondary outcome
LOS diagnosis in NICU preterm neonates, whose weight at birth is less than 1500 grams, of at least 7 days of life, with suggestive clinical signs, confirmed by adjudication committee.
Time frame: Hour 48
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2025.
- Results publication: PubMed 37371798Pons S, Trouillet-Assant S, Subtil F, Abbas-Chorfa F, Cornaton E, Berthiot A, Galletti S, Plat A, Rapin S, Trapes L, Generenaz L, Brengel-Pesce K, Callies A, Plaisant F, Claris O, Portefaix A, Flamant C, Butin M. Performance of 11 Host Biomarkers Alone or in Combination in the Diagnosis of Late-Onset Sepsis in Hospitalized Neonates: The Prospective EMERAUDE Study. Biomedicines. 2023 Jun 13;11(6):1703. doi: 10.3390/biomedicines11061703.
- 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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Diagnostic performances of biomarkers combination in people with Late-Onset Neonatal Sepsis, run by Hospices Civils de Lyon at 2 sites in France.
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 3 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: finished, as of the sponsor's last update on 4 Sep 2025. 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 France. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
LOS diagnosis in NICU newborns of at least 7 days of life with suggestive clinical signs, confirmed by adjudication committee (time frame: hour 48). 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 NCT03299751, 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 4 Sep 2025.