<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03299751</url>
  </required_header>
  <id_info>
    <org_study_id>69HCL17_0492</org_study_id>
    <nct_id>NCT03299751</nct_id>
  </id_info>
  <brief_title>Evaluation of bioMarkErs to Reduce Antibiotics Use in hospitalizeD nEonates</brief_title>
  <acronym>EMERAUDE</acronym>
  <official_title>Evaluation of Biomarkers Combination Performance for the Diagnosis of Neonatal Sepsis in NICU Hospitalized Newborns</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospices Civils de Lyon</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospices Civils de Lyon</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Late-onset neonatal sepsis (LOS), occurring in newborn of at least 7 days of life, is&#xD;
      frequently observed in Neonatal Intensive Care Units (NICUs) and potentially severe&#xD;
      (mortality, neurologic and respiratory impairments).&#xD;
&#xD;
      Despite its high prevalence, a reliable diagnostic remains difficult. Currently, nonspecific&#xD;
      clinical signs that might be linked to other neonatal conditions, such as prematurity and&#xD;
      birth defects are used to determine the diagnosis of LOS. Laboratory results of biological&#xD;
      markers, such as C-Reactive Protein (CRP) and Procalcitonin (PCT) are often delayed in&#xD;
      comparison with LOS onset. Blood culture results are too late and lack sensitivity.&#xD;
&#xD;
      Excessive antibiotic use is observed in a large proportion of NICU hospitalized newborns.&#xD;
      This results in an increased antibiotic resistance, microbiota modification, neonatal&#xD;
      complications (pulmonary, ophthalmologic and neurologic) and mortality.&#xD;
&#xD;
      The primary objective is to identify, on a cohort of 250 patients, the optimal biomarker&#xD;
      combination with good diagnostic performance (i.e. with maximal Area Under the ROC Curve) to&#xD;
      early exclude a LOS diagnostic in newborns of at least 7 days of life with suggestive signs.&#xD;
&#xD;
      This identification will be carried out, as a secondary objective, with a sub-group of&#xD;
      pre-term neonates whose birth weight is less than 1500 grams. The diagnostic value of the&#xD;
      clinical signs that are suggestive of LOS will also be determined (sensitivity, specificity,&#xD;
      negative and positive predictive values).&#xD;
&#xD;
      Once identified, the biomarker combination is expected to reduce unjustified antibiotic use.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 22, 2017</start_date>
  <completion_date type="Actual">November 20, 2020</completion_date>
  <primary_completion_date type="Actual">November 20, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>LOS diagnosis in NICU newborns of at least 7 days of life with suggestive clinical signs, confirmed by adjudication committee</measure>
    <time_frame>hour 48</time_frame>
    <description>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.&#xD;
The diagnostic performance of the biomarkers combination will be based on the adjudication committee</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>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.</measure>
    <time_frame>Hour 48</time_frame>
    <description>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.&#xD;
The diagnostic performance of the biomarkers combination will be based on the adjudication committee classification (gold standard).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">233</enrollment>
  <condition>Late-Onset Neonatal Sepsis</condition>
  <arm_group>
    <arm_group_label>NICU newborns of at least 7 days of life with suggestive signs</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Diagnostic performances of biomarkers combination</intervention_name>
    <description>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.&#xD;
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.&#xD;
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.</description>
    <arm_group_label>NICU newborns of at least 7 days of life with suggestive signs</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  patients hospitalized in NICU;&#xD;
&#xD;
          -  patients with suggestive signs of LOS including at least one of the following:&#xD;
&#xD;
             o Fever &gt; 38°C; tachycardia &gt; 160bpm160 bpm; capillary refill time &gt; 3 seconds; grey&#xD;
             and/or pale skin complexion; apnea/ bradycardia syndrome,; bloating; rectal bleeding;&#xD;
             hypotonia; lethargy; seizures without other obvious cause; increased ventilatory&#xD;
             support and/or increased FiO2; cutaneous rash; inflammation at the needle-puncture&#xD;
             site of the central venous catheter;&#xD;
&#xD;
          -  patients with a standard of care blood sampling, including at least a blood culture;&#xD;
&#xD;
          -  consent form signed by at least one parent/ legal representative.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  patients treated with antibiotics for a bacteriologically confirmed infection at the&#xD;
             moment of/ or 48 hours before blood sampling&#xD;
&#xD;
          -  patients who underwent surgery during the 7 days prior to inclusion&#xD;
&#xD;
          -  patients vaccinated during the 7 days prior to inclusion&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>7 Days</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Hospices Civils de Lyon</name>
      <address>
        <city>Bron</city>
        <zip>69500</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Nantes</name>
      <address>
        <city>Nantes</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>September 28, 2017</study_first_submitted>
  <study_first_submitted_qc>September 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 3, 2017</study_first_posted>
  <last_update_submitted>September 16, 2022</last_update_submitted>
  <last_update_submitted_qc>September 16, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>neonatal sepsis</keyword>
  <keyword>biomarker combination</keyword>
  <keyword>diagnostic</keyword>
  <keyword>antibiotic use</keyword>
  <keyword>newborn</keyword>
  <keyword>preterm neonates</keyword>
  <keyword>NICU</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sepsis</mesh_term>
    <mesh_term>Neonatal Sepsis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03299751
org study id: 69HCL17_0492
nct id: NCT03299751
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
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
description: 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
measure: 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
description: 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).
arm group label: NICU newborns of at least 7 days of life with suggestive signs
arm group type: Experimental
intervention type: Biological
intervention name: Diagnostic performances of biomarkers combination
description: 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.
arm group label: NICU newborns of at least 7 days of life with suggestive signs
criteria: 
gender: All
minimum age: 7 Days
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
country: France
responsible party type: Sponsor
mesh term: Sepsis
mesh term: Neonatal Sepsis
sharing ipd: No