Predicting EONS in PPROM Patients (PEONS)

Prediction of Early-Onset Neonatal Sepsis (EONS) in Pregnant Women With Preterm Premature Rupture of Membranes (PPROM) by Vaginal Microbiome Analysis - a Pilot Study

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).

Study Overview

• Status: Recruiting
• Conditions: PPROM; Early-Onset Neonatal Sepsis
• Intervention / Treatment: Diagnostic test: microbiome analysis; Diagnostic test: Conventional cultures; Diagnostic test: CAAP48 measurement

• Study Type: Observational
• Enrollment (Anticipated): 150

Contacts and Locations

• Study Contact: Name: Ekkehard Schleußner, Prof. Dr.; Phone Number: 932 920 +49 3641; Email: gabriele.schack@med.uni-jena.de
• Study Contact Backup: Name: Janine Zöllkau, Dr.; Phone Number: 932 92 18 +49 3641; Email: studien.geburtsmedizin@med.uni-jena.de

Study Locations

• Germany
  • Saxony-Anhalt
    • Halle (Saale), Saxony-Anhalt, Germany, 06097
      • Recruiting
      • University Hospital Halle/s.
      • Contact: Michael Bergner; Phone Number: 557 3250 +49345; Email: michael.bergner@uk-halle.de
  • Thuringe
    • Jena, Thuringe, Germany, 0774
      • Recruiting
      • Jena University Hospital
      • Contact: Jana Pastuschek, Dipl. Biol. M.Sc.; Phone Number: 329295 +49 3641; Email: jana.pastuschek@med.uni-jena.de
      • Contact: Yvonne Heimann, M.Sc.; Phone Number: 390 868 +49 3641; Email: yvonne.heimann@med.uni-jena.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

PPROM cohort = PPROM patients (hospitalization between 22+0 - 34+0 weeks of gestation) and their born preterm neonates, n = 65

• Subgroup 1: with EONS, n = 15
• Subgroup 2: without EONS, n = 50

Description

Inclusion Criteria:

• full age pregnant woman with PPROM and their born preterm infants
• hospitalization between 22+0 and 34+0 weeks of gestation
• multipara possible

Exclusion Criteria:

• hospitalization with PPROM before limit of viability are reached
• intrauterine fetal death
• no study agreement
• not able to consent

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
neonates with signs of EONS	Diagnostic test: microbiome analysis; 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.; Diagnostic test: Conventional cultures; For every sample taken for microbiome analysis, a conventional culture is taken as control.; Diagnostic test: CAAP48 measurement; 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).
neonates without signs of EONS	Diagnostic test: microbiome analysis; 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.; Diagnostic test: Conventional cultures; For every sample taken for microbiome analysis, a conventional culture is taken as control.; Diagnostic test: CAAP48 measurement; 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).
pregnant women with PPROM	Diagnostic test: microbiome analysis; 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.; Diagnostic test: Conventional cultures; For every sample taken for microbiome analysis, a conventional culture is taken as control.; Diagnostic test: CAAP48 measurement; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Development of EONS	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.	3 days after delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
vaginal CST in PPROM	the specific patterns of vaginal CST and vaginal microbiota composition (microbiome) in PPROM	until delivery
neonatal microbial colonisation	neonatal microbial colonisation (microbiome) on 1st and 2nd day of life	up to 2 days after delivery

Collaborators and Investigators

• Sponsor: Jena University Hospital
• Collaborators: Center of Fetal Surgery, University Hospital Halle Saale; Section for Neonatology and Pediatric Intensive Care, University Hospital Halle Saale

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2019
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: January 23, 2019
• First Submitted That Met QC Criteria: January 25, 2019
• First Posted (Actual): January 28, 2019

Study Record Updates

• Last Update Posted (Actual): April 14, 2023
• Last Update Submitted That Met QC Criteria: April 12, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Infant, Newborn, Diseases; Sepsis; Neonatal Sepsis
• Other Study ID Numbers: KG-PEONS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No