<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/NCT03819192</url>
  </required_header>
  <id_info>
    <org_study_id>KG-PEONS</org_study_id>
    <nct_id>NCT03819192</nct_id>
  </id_info>
  <brief_title>Predicting EONS in PPROM Patients</brief_title>
  <acronym>PEONS</acronym>
  <official_title>Prediction of Early-Onset Neonatal Sepsis (EONS) in Pregnant Women With Preterm Premature Rupture of Membranes (PPROM) by Vaginal Microbiome Analysis - a Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jena University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Center of Fetal Surgery, University Hospital Halle Saale</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Section for Neonatology and Pediatric Intensive Care, University Hospital Halle Saale</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Jena University Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      An EONS occurred in nearly 14-22 % of the preterm infant of pregnant women with PPROM. To&#xD;
      this day no risk prediction is established. The main aim of this pilot study is generating&#xD;
      primary data with a focus on the vaginal microbiome to set-up a prospective, multi-centre&#xD;
      trial investigating the role of the vaginal microbiome for future EONS risk prediction.&#xD;
&#xD;
      The planned PEONS pilot trial is subdivided in three Work packages:&#xD;
&#xD;
        1. Recruitment, sample collection and routine clinical diagnostics&#xD;
&#xD;
        2. Microbiome analysis by 16S rRNA&#xD;
&#xD;
        3. Microbiome/ Metagenome analysis by &quot;Nanopore&quot; (proof-of-principle) and will enroll women&#xD;
           with a PPROM event hospitalized between 22+0 and 34+0 weeks of gestation and neonates&#xD;
           with signs of EONS (Subgroup 1) and without signs of EONS (Subgroup 2).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 1, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Development of EONS</measure>
    <time_frame>3 days after delivery</time_frame>
    <description>Primary outcome is the development of EONS defined as the presence of confirmed or suspected sepsis at ≤3 days after birth for which prolonged neonatal antibiotic treatment beyond 72 hours. Confirmed sepsis is established by positive blood cultures whilst suspected sepsis is diagnosed in the presence of clinical suspicion of sepsis (lethargy, apnoea, respiratory distress, hypotension (mean arterial blood pressure (MAD) &lt; gestational age), hypoperfusion and shock) supported by elevated neonatal C-reactive protein (CRP), interleukin-6 (IL6) or blood film suggestive of bacteraemia.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>vaginal CST in PPROM</measure>
    <time_frame>until delivery</time_frame>
    <description>the specific patterns of vaginal CST and vaginal microbiota composition (microbiome) in PPROM</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>neonatal microbial colonisation</measure>
    <time_frame>up to 2 days after delivery</time_frame>
    <description>neonatal microbial colonisation (microbiome) on 1st and 2nd day of life</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Anticipated">150</enrollment>
  <condition>PPROM</condition>
  <condition>Early-Onset Neonatal Sepsis</condition>
  <arm_group>
    <arm_group_label>neonates with signs of EONS</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>neonates without signs of EONS</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>pregnant women with PPROM</arm_group_label>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>microbiome analysis</intervention_name>
    <description>From all full age pregnant women with PPROM enrolled in this study vaginal smear samples will be taken at three time points:&#xD;
directly after hospitalization&#xD;
5-7 days after beginning of antibiotic treatment&#xD;
24 h before birth&#xD;
The microbiome of the neonates of these women will be analysed out of pharyngeal and rectal swabs and umbilical cord blood taken directly after birth and additionally out of the first Meconium.</description>
    <arm_group_label>neonates with signs of EONS</arm_group_label>
    <arm_group_label>neonates without signs of EONS</arm_group_label>
    <arm_group_label>pregnant women with PPROM</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Conventional cultures</intervention_name>
    <description>For every sample taken for microbiome analysis, a conventional culture is taken as control.</description>
    <arm_group_label>neonates with signs of EONS</arm_group_label>
    <arm_group_label>neonates without signs of EONS</arm_group_label>
    <arm_group_label>pregnant women with PPROM</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>CAAP48 measurement</intervention_name>
    <description>CAAP48 is an identified sepsis marker in adult patients. The samples are taken dependent on clinical monitoring to compare CAAP48 with established inflammation markers (CRP, IL-6, White blood cell count, Procalcitonin).</description>
    <arm_group_label>neonates with signs of EONS</arm_group_label>
    <arm_group_label>neonates without signs of EONS</arm_group_label>
    <arm_group_label>pregnant women with PPROM</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        PPROM cohort = PPROM patients (hospitalization between 22+0 - 34+0 weeks of gestation) and&#xD;
        their born preterm neonates, n = 65&#xD;
&#xD;
          -  Subgroup 1: with EONS, n = 15&#xD;
&#xD;
          -  Subgroup 2: without EONS, n = 50&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  full age pregnant woman with PPROM and their born preterm infants&#xD;
&#xD;
          -  hospitalization between 22+0 and 34+0 weeks of gestation&#xD;
&#xD;
          -  multipara possible&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  hospitalization with PPROM before limit of viability are reached&#xD;
&#xD;
          -  intrauterine fetal death&#xD;
&#xD;
          -  no study agreement&#xD;
&#xD;
          -  not able to consent&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Ekkehard Schleußner, Prof. Dr.</last_name>
    <phone>+49 3641</phone>
    <phone_ext>932 920</phone_ext>
    <email>gabriele.schack@med.uni-jena.de</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Janine Zöllkau, Dr.</last_name>
    <phone>+49 3641</phone>
    <phone_ext>932 92 18</phone_ext>
    <email>studien.geburtsmedizin@med.uni-jena.de</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University Hospital Halle/s.</name>
      <address>
        <city>Halle (Saale)</city>
        <state>Saxony-Anhalt</state>
        <zip>06097</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michael Bergner</last_name>
      <phone>+49345</phone>
      <phone_ext>557 3250</phone_ext>
      <email>michael.bergner@uk-halle.de</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Jena University Hospital</name>
      <address>
        <city>Jena</city>
        <state>Thuringe</state>
        <zip>0774</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jana Pastuschek, Dipl. Biol. M.Sc.</last_name>
      <phone>+49 3641</phone>
      <phone_ext>329295</phone_ext>
      <email>jana.pastuschek@med.uni-jena.de</email>
    </contact>
    <contact_backup>
      <last_name>Yvonne Heimann, M.Sc.</last_name>
      <phone>+49 3641</phone>
      <phone_ext>390 868</phone_ext>
      <email>yvonne.heimann@med.uni-jena.de</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>January 23, 2019</study_first_submitted>
  <study_first_submitted_qc>January 25, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <last_update_submitted>April 12, 2023</last_update_submitted>
  <last_update_submitted_qc>April 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 14, 2023</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>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/NCT03819192
org study id: KG-PEONS
nct id: NCT03819192
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
An EONS occurred in nearly 14-22 % of the preterm infant of pregnant women with PPROM. To
      this day no risk prediction is established. The main aim of this pilot study is generating
      primary data with a focus on the vaginal microbiome to set-up a prospective, multi-centre
      trial investigating the role of the vaginal microbiome for future EONS risk prediction.

      The planned PEONS pilot trial is subdivided in three Work packages:

        1. Recruitment, sample collection and routine clinical diagnostics

        2. Microbiome analysis by 16S rRNA

        3. Microbiome/ Metagenome analysis by "Nanopore" (proof-of-principle) and will enroll women
           with a PPROM event hospitalized between 22+0 and 34+0 weeks of gestation and neonates
           with signs of EONS (Subgroup 1) and without signs of EONS (Subgroup 2).
observational model: Case-Control
time perspective: Prospective
measure: Development of EONS
time frame: 3 days after delivery
description: Primary outcome is the development of EONS defined as the presence of confirmed or suspected sepsis at ≤3 days after birth for which prolonged neonatal antibiotic treatment beyond 72 hours. Confirmed sepsis is established by positive blood cultures whilst suspected sepsis is diagnosed in the presence of clinical suspicion of sepsis (lethargy, apnoea, respiratory distress, hypotension (mean arterial blood pressure (MAD) < gestational age), hypoperfusion and shock) supported by elevated neonatal C-reactive protein (CRP), interleukin-6 (IL6) or blood film suggestive of bacteraemia.
measure: vaginal CST in PPROM
time frame: until delivery
description: the specific patterns of vaginal CST and vaginal microbiota composition (microbiome) in PPROM
measure: neonatal microbial colonisation
time frame: up to 2 days after delivery
description: neonatal microbial colonisation (microbiome) on 1st and 2nd day of life
arm group label: neonates with signs of EONS
arm group label: neonates without signs of EONS
arm group label: pregnant women with PPROM
intervention type: Diagnostic Test
intervention name: microbiome analysis
description: From all full age pregnant women with PPROM enrolled in this study vaginal smear samples will be taken at three time points:
directly after hospitalization
5-7 days after beginning of antibiotic treatment
24 h before birth
The microbiome of the neonates of these women will be analysed out of pharyngeal and rectal swabs and umbilical cord blood taken directly after birth and additionally out of the first Meconium.
arm group label: neonates with signs of EONS
arm group label: neonates without signs of EONS
arm group label: pregnant women with PPROM
intervention type: Diagnostic Test
intervention name: Conventional cultures
description: For every sample taken for microbiome analysis, a conventional culture is taken as control.
arm group label: neonates with signs of EONS
arm group label: neonates without signs of EONS
arm group label: pregnant women with PPROM
intervention type: Diagnostic Test
intervention name: CAAP48 measurement
description: CAAP48 is an identified sepsis marker in adult patients. The samples are taken dependent on clinical monitoring to compare CAAP48 with established inflammation markers (CRP, IL-6, White blood cell count, Procalcitonin).
arm group label: neonates with signs of EONS
arm group label: neonates without signs of EONS
arm group label: pregnant women with PPROM
study pop: 
sampling method: Probability Sample
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ekkehard Schleußner, Prof. Dr.
phone: +49 3641
phone ext: 932 920
email: gabriele.schack@med.uni-jena.de
last name: Janine Zöllkau, Dr.
phone: +49 3641
phone ext: 932 92 18
email: studien.geburtsmedizin@med.uni-jena.de
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
country: Germany
responsible party type: Sponsor
mesh term: Sepsis
mesh term: Neonatal Sepsis
sharing ipd: No