PEONS

Vorhersage einer neonatalen Sepsis (EONS) nach frühem vorzeitigen Blasensprung durch vaginale Mikrobiom-Analyse

Applicant/ Coordinating investigator	Prof. Dr. med. Ekkehard Schleußner, Department of Obstetrics, Jena University Hospital and Priv.-Doz. Dr. med. Kristin Dawczynski, Department of Pediatrics, Unit Neonatology, Jena University Hospital
Title of trial	PEONS pilot trial - Prediction of Early-Onset Neonatal Sepsis (EONS) in pregnant women with Preterm Premature Rupture of membranes (PPROM) by vaginal microbiome analysis – a pilot study
Research Field	B – Novel strategies for antimicrobial treatment D – Outcome Research
Medical condition	PPROM (Preterm Premature Rupture of Membranes) AIS (Amniotic Infection Syndrome), EONS (Early-Onset Neonatal Sepsis)
Objective(s)	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 four Work packages Chapter 3.6: 1 – Recruitment, sample collection and routine clinical diagnostics 2 – Microbiome analysis by 16S rRNA 3 – Microbiome/ Metagenome analysis by “Nanopore” (proof-of-principle) 4 – Blood biomarkers (CAAP48 peptide analysis) and will enroll hospitalized women with a PPROM event and between 22+0 and 34+0 weeks of gestation and neonates with signs of EONS (Subgroup 1) and without signs of EONS (Subgroup 2). Chapter 2.2
Intervention(s)	Experimental intervention/index test: Non-invasive sampling of vaginal fluids from PPROM patients (T0, T1, T2), sampling of umbilical cord blood (CB) as well as sampling of rectal (NR) and pharyngeal (NP) swabs and first meconium (NM) from the neonate. Control intervention/reference test: not planned / not applicable Follow-up per patient: Swabs Maternal: three times (T0= first clinical examination after PPROM event and before antibiotic therapy, T1= 5-7 days after start of antibiotic therapy, T2= within 24 h before delivery) Cord blood: one time (CB = delivery) Neonatal: two times (NP and NR = 1st day of life, NM= 1st - 2nd day of life) Plasma Maternal: one time, dependent of clinical monitoring Cord blood: one time, delivery Neonatal one time, dependent of clinical monitoring Duration of intervention per patient: Swab sampling: 5 min each; maternal and neonatal: each 3 x 5 min = 15 min; cord blood: 1 x 5 min = 5 min Plasma sampling: maternal and neonatal: clinical blood monitoring/ no additional intervention, cord blood: 1 x 5 min = 5 min
Key inclusion and exclusion criteria	Key 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 Key exclusion criteria: • hospitalization with PPROM before limit of viability are reached • intrauterine fetal death • no study agreement • not able to consent
Outcome(s)	Primary efficacy endpoint: The development of EONS defined as the presence of confirmed or suspected sepsis at ≤3 days after birth for which neonatal antibiotic treatment was prolonged beyond 72 hours. Chapter 3.3
Study type / design	Non-interventional, observational, prospective, controlled, non-randomized, Masking: Open-label Purpose: Diagnostic, prognostic
Biostatistical and bioinformatic analysis	General: Center for Clinical Studies (ZKS)/ Core Unit “Clinical Epidemiology”, University Hospital Jena under the guidance of Prof. Dr. André Scherag Vaginal and neonatal microbiome: Prof. Dr. Dietmar Pieper, Helmholtz Center for Infection Research (HZI), Braunschweig and Dr. Oliwia Makarewicz, Research Lab, Institute for Infectious Diseases and Infection Control (IIMK), Jena University Hospital according to e.g., Camarinha-Silva et al. and Schulz et al. (genera and species taxonomic levels). n = 75 n = 67 n = 65
Sample size	To be assessed for eligibility: n = 75 To be assigned to the trial: n = 67 To be analysed: n = 65
Trial duration	First patient in to last patient out (months): 12 month Duration of the entire trial (months): 18 month Recruitment period (months): 12 month
Participating centres	n = 2 (Jena University Hospital, University Hospital Halle/S.)