<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/NCT04470596</url>
  </required_header>
  <id_info>
    <org_study_id>CLEEONI</org_study_id>
    <nct_id>NCT04470596</nct_id>
  </id_info>
  <brief_title>Clinical Evaluation of Early Onset Neonatal Infection</brief_title>
  <acronym>CLEEONI</acronym>
  <official_title>Clinical Evaluation of Early Onset Neonatal Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fondation Hôpital Saint-Joseph</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fondation Hôpital Saint-Joseph</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>
      Early bacterial neonatal infection (INBP) defined as occurring in the first 3 days and by&#xD;
      extension in the first week of life, remains to this day the leading cause of neonatal&#xD;
      morbidity and mortality in developed countries. The germs most frequently found are&#xD;
      Streptococcus B (SB) for term newborns (&gt; 37 Weeks of Amenorrhea SA) and Escherichia coli (E.&#xD;
      coli) in premature newborns. Although in France, its incidence of 0.4 / 1000 is lower than in&#xD;
      other developed countries (0.8 / 1000 general incidence), it remains a major public health&#xD;
      concern.&#xD;
&#xD;
      The infection criteria were defined by the National Agency for Health Accreditation and&#xD;
      Assessment (ANAES) in 2002, allowing to differentiate between proven infections and highly&#xD;
      probable cases of infection. Infection is considered to be proven when SB or E. coli is&#xD;
      detected in blood culture or in cerebrospinal fluid. An infection is considered to be highly&#xD;
      probable in the event of association of clinical signs (fever, polypnea, desaturation,&#xD;
      tachycardia, etc.) evoking a beginning sepsis associating with a disturbance of the&#xD;
      biological balance sheet (elevation of CRP, hyperleukocytosis, evidence of colonization on&#xD;
      peripheral samples). These criteria remain valid to this day to define the infection.&#xD;
&#xD;
      In order to define the newborns to be monitored, risk factors were established after a review&#xD;
      of the literature in 2002. They make it possible to decide on diagnostic management and / or&#xD;
      the setting up of a treatment.&#xD;
&#xD;
      Since the recommendations of the ANAES of 2002, the rule, from the presence of a major&#xD;
      criterion, was to carry out bacteriological samples peripheral to the birth (gastric liquid,&#xD;
      swab of ear and anus) and to systematically collect a CRP of the child between H12 and H48.&#xD;
      In the presence of an isolated minor risk factor, simple clinical monitoring (routine) was&#xD;
      recommended for 48 hours without deciding firmly on the need for a biological sample.&#xD;
      However, it is important to note that these two categories of signs are defined and&#xD;
      classified in descending order of risk. This classification does not prejudge a systematic&#xD;
      therapeutic attitude. In many situations, the choice is actually left to the practitioner&#xD;
      depending on the context.&#xD;
&#xD;
      In 2017, new recommendations were implemented by the French Society of Pediatrics (SFP) and&#xD;
      the French Society of Neonatology (SFN) regarding the prevention of INBP. These take up the&#xD;
      risk factors of the 2002 ANAES by adding PCR SB at the same level as the traditional PV. They&#xD;
      define 3 categories of children according to the risk of INBP and the associated care.&#xD;
&#xD;
      In most cases, these new practices make it possible to dispense with costly blood and&#xD;
      bacteriological samples, which cause discomfort and pain for children. In addition, the use&#xD;
      of gastric fluid is not internationally validated, its use in the management case remains&#xD;
      very controversial. In case of delayed CRP or positive peripheral samples to the germs&#xD;
      generated, and even in the absence of clinical signs, antibiotic therapy was almost&#xD;
      systematically initiated. Unnecessary exposure to antibiotics promotes the development of&#xD;
      bacteriological resistance and unbalances the neonatal flora.&#xD;
&#xD;
      Following the implementation of these new recommendations at the Notre Dame de Bon Secours&#xD;
      maternity hospital, which is the case in few centers today and no national survey has yet&#xD;
      been carried out on their application, it therefore seems necessary to us evaluate the&#xD;
      application of these new recommendations and verify that they allow the detection of all&#xD;
      probable or proven infections.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 9, 2020</start_date>
  <completion_date type="Actual">December 31, 2021</completion_date>
  <primary_completion_date type="Actual">December 31, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Newborn screening</measure>
    <time_frame>Month 3</time_frame>
    <description>This outcome corresponds to percentage of asymptomatic infants at risk for INBP in whom close clinical surveillance has shown no signs of infectious disease, and who have had a probable or proven infection between the discharge from maternity and the age of 1 and 3 months.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>negative predictive value of SB PCR for children with proven group B Streptococcus infection</measure>
    <time_frame>Month 3</time_frame>
    <description>This outcome corresponds to percentage of newborns infected with group B Streptococcus (proven infection) during the postnatal stay and whose mothers' PCRs were negative per partum, whether or not they were monitored.</description>
  </secondary_outcome>
  <enrollment type="Actual">936</enrollment>
  <condition>Newborn</condition>
  <eligibility>
    <study_pop>
      <textblock>
        - Newborns over 36 weeks old, born between 01/01/2019 and 31/12/2019 at the GHPSJ&#xD;
        maternity, having benefited from close infectious surveillance according to the criteria of&#xD;
        the 2017 recommendations (Groups B and C).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Newborns over 36 weeks old, born between 01/01/2019 and 31/12/2019 at the GHPSJ&#xD;
             maternity&#xD;
&#xD;
          -  Newborn having benefited from close infectious surveillance according to the criteria&#xD;
             of the 2017 recommendations (Groups B and C)&#xD;
&#xD;
          -  In birth suites near their mother&#xD;
&#xD;
          -  Francophone parents&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Parents objecting to participation in the study&#xD;
&#xD;
          -  Parents deprived of their liberty&#xD;
&#xD;
          -  Parents under guardianship or curatorship&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>36 Weeks</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Elizabeth WALTER, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fondation Hôpital Saint-Joseph</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Groupe Hospitalier Paris Saint-Joseph</name>
      <address>
        <city>Paris</city>
        <zip>75014</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <results_reference>
    <citation>Weston EJ, Pondo T, Lewis MM, Martell-Cleary P, Morin C, Jewell B, Daily P, Apostol M, Petit S, Farley M, Lynfield R, Reingold A, Hansen NI, Stoll BJ, Shane AL, Zell E, Schrag SJ. The burden of invasive early-onset neonatal sepsis in the United States, 2005-2008. Pediatr Infect Dis J. 2011 Nov;30(11):937-41. doi: 10.1097/INF.0b013e318223bad2.</citation>
    <PMID>21654548</PMID>
  </results_reference>
  <results_reference>
    <citation>Stoll BJ, Hansen NI, Sanchez PJ, Faix RG, Poindexter BB, Van Meurs KP, Bizzarro MJ, Goldberg RN, Frantz ID 3rd, Hale EC, Shankaran S, Kennedy K, Carlo WA, Watterberg KL, Bell EF, Walsh MC, Schibler K, Laptook AR, Shane AL, Schrag SJ, Das A, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Early onset neonatal sepsis: the burden of group B Streptococcal and E. coli disease continues. Pediatrics. 2011 May;127(5):817-26. doi: 10.1542/peds.2010-2217. Epub 2011 Apr 25. Erratum In: Pediatrics. 2011 Aug;128(2):390.</citation>
    <PMID>21518717</PMID>
  </results_reference>
  <results_reference>
    <citation>El Helali N, Nguyen JC, Ly A, Giovangrandi Y, Trinquart L. Diagnostic accuracy of a rapid real-time polymerase chain reaction assay for universal intrapartum group B streptococcus screening. Clin Infect Dis. 2009 Aug 1;49(3):417-23. doi: 10.1086/600303.</citation>
    <PMID>19580414</PMID>
  </results_reference>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>July 9, 2020</study_first_submitted>
  <study_first_submitted_qc>July 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 14, 2020</study_first_posted>
  <last_update_submitted>December 31, 2021</last_update_submitted>
  <last_update_submitted_qc>December 31, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
  </condition_browse>
  <!-- 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/NCT04470596
org study id: CLEEONI
nct id: NCT04470596
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Early bacterial neonatal infection (INBP) defined as occurring in the first 3 days and by
      extension in the first week of life, remains to this day the leading cause of neonatal
      morbidity and mortality in developed countries. The germs most frequently found are
      Streptococcus B (SB) for term newborns (> 37 Weeks of Amenorrhea SA) and Escherichia coli (E.
      coli) in premature newborns. Although in France, its incidence of 0.4 / 1000 is lower than in
      other developed countries (0.8 / 1000 general incidence), it remains a major public health
      concern.

      The infection criteria were defined by the National Agency for Health Accreditation and
      Assessment (ANAES) in 2002, allowing to differentiate between proven infections and highly
      probable cases of infection. Infection is considered to be proven when SB or E. coli is
      detected in blood culture or in cerebrospinal fluid. An infection is considered to be highly
      probable in the event of association of clinical signs (fever, polypnea, desaturation,
      tachycardia, etc.) evoking a beginning sepsis associating with a disturbance of the
      biological balance sheet (elevation of CRP, hyperleukocytosis, evidence of colonization on
      peripheral samples). These criteria remain valid to this day to define the infection.

      In order to define the newborns to be monitored, risk factors were established after a review
      of the literature in 2002. They make it possible to decide on diagnostic management and / or
      the setting up of a treatment.

      Since the recommendations of the ANAES of 2002, the rule, from the presence of a major
      criterion, was to carry out bacteriological samples peripheral to the birth (gastric liquid,
      swab of ear and anus) and to systematically collect a CRP of the child between H12 and H48.
      In the presence of an isolated minor risk factor, simple clinical monitoring (routine) was
      recommended for 48 hours without deciding firmly on the need for a biological sample.
      However, it is important to note that these two categories of signs are defined and
      classified in descending order of risk. This classification does not prejudge a systematic
      therapeutic attitude. In many situations, the choice is actually left to the practitioner
      depending on the context.

      In 2017, new recommendations were implemented by the French Society of Pediatrics (SFP) and
      the French Society of Neonatology (SFN) regarding the prevention of INBP. These take up the
      risk factors of the 2002 ANAES by adding PCR SB at the same level as the traditional PV. They
      define 3 categories of children according to the risk of INBP and the associated care.

      In most cases, these new practices make it possible to dispense with costly blood and
      bacteriological samples, which cause discomfort and pain for children. In addition, the use
      of gastric fluid is not internationally validated, its use in the management case remains
      very controversial. In case of delayed CRP or positive peripheral samples to the germs
      generated, and even in the absence of clinical signs, antibiotic therapy was almost
      systematically initiated. Unnecessary exposure to antibiotics promotes the development of
      bacteriological resistance and unbalances the neonatal flora.

      Following the implementation of these new recommendations at the Notre Dame de Bon Secours
      maternity hospital, which is the case in few centers today and no national survey has yet
      been carried out on their application, it therefore seems necessary to us evaluate the
      application of these new recommendations and verify that they allow the detection of all
      probable or proven infections.
observational model: Cohort
time perspective: Retrospective
measure: Newborn screening
time frame: Month 3
description: This outcome corresponds to percentage of asymptomatic infants at risk for INBP in whom close clinical surveillance has shown no signs of infectious disease, and who have had a probable or proven infection between the discharge from maternity and the age of 1 and 3 months.
measure: negative predictive value of SB PCR for children with proven group B Streptococcus infection
time frame: Month 3
description: This outcome corresponds to percentage of newborns infected with group B Streptococcus (proven infection) during the postnatal stay and whose mothers' PCRs were negative per partum, whether or not they were monitored.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 36 Weeks
maximum age: N/A
healthy volunteers: No
last name: Elizabeth WALTER, MD
role: Principal Investigator
affiliation: Fondation Hôpital Saint-Joseph
facility: 
country: France
citation: Weston EJ, Pondo T, Lewis MM, Martell-Cleary P, Morin C, Jewell B, Daily P, Apostol M, Petit S, Farley M, Lynfield R, Reingold A, Hansen NI, Stoll BJ, Shane AL, Zell E, Schrag SJ. The burden of invasive early-onset neonatal sepsis in the United States, 2005-2008. Pediatr Infect Dis J. 2011 Nov;30(11):937-41. doi: 10.1097/INF.0b013e318223bad2.
PMID: 21654548
citation: Stoll BJ, Hansen NI, Sanchez PJ, Faix RG, Poindexter BB, Van Meurs KP, Bizzarro MJ, Goldberg RN, Frantz ID 3rd, Hale EC, Shankaran S, Kennedy K, Carlo WA, Watterberg KL, Bell EF, Walsh MC, Schibler K, Laptook AR, Shane AL, Schrag SJ, Das A, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Early onset neonatal sepsis: the burden of group B Streptococcal and E. coli disease continues. Pediatrics. 2011 May;127(5):817-26. doi: 10.1542/peds.2010-2217. Epub 2011 Apr 25. Erratum In: Pediatrics. 2011 Aug;128(2):390.
PMID: 21518717
citation: El Helali N, Nguyen JC, Ly A, Giovangrandi Y, Trinquart L. Diagnostic accuracy of a rapid real-time polymerase chain reaction assay for universal intrapartum group B streptococcus screening. Clin Infect Dis. 2009 Aug 1;49(3):417-23. doi: 10.1086/600303.
PMID: 19580414
responsible party type: Sponsor
mesh term: Infections