Clinical trial NCT03371056: Maternal- Fetal Infection
Official title: Innovative Strategies for Perinatal Infectious Risk Reduction
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Neonatal Infection
Keywords: Neonatal infections
maternal-fetal infection
group B streptococcus
vaginal sample
antibiotic prophylaxis
bacterial resistance
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Bforcure
name: BPIfrance
name: Institut National de la Santé Et de la Recherche Médicale, France
name: Institut Cochin
First posted: 2017-12-13
Enrollment: 2600
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: There are 4 pre-specified groups
Primary purpose: SCREENING

Brief summary: The purpose of the protocol is to validate a novel point of care multiplex system to detect and characterize microorganisms responsible for neonatal sepsis, as well as biomarkers of infection, from a simple vaginal sample, in order to improve the prevention of perinatal bacterial infections.

Detailed description: Early-onset neonatal sepsis (EOS) is a major global public health challenge. Prevention during pregnancy and delivery, early diagnosis and treatment of perinatal infections are essential to avoid EOS. Risk factors for include prematurity, maternal Group B streptococcus (GBS) colonization, premature rupture of membranes (PROM), and chorioamnionitis. Screening and intrapartum antimicrobial prophylaxis administered to GBS-colonized women has reduced early onset GBS infections. However, other pathogens are frequently involved in EOS following preterm PROM and preterm birth (PTB), such as Gram-negative bacteria and Staphylococci, which are not covered by penicillin prophylaxis. The prevalence of neonatal infection arising from antibiotic-resistant bacteria is increasing, thus the challenge is to eliminate the widespread unnecessary use of broad-spectrum antibiotics to treat non-infected infants, while recognizing when antibiotics are truly needed. Rapid diagnostic test(s) to detect and quantify specifically pathogens in vaginal samples, could be a major breakthrough. Several rT- PCR ( reverse Transcriptase Polymerase Chain Reaction) tests are on the market, however so far no test is able to detect, quantify and characterize in terms of antibiotic resistance and virulence genes, a range of pathogens.

A novel multiplex platform, using microfluidics technology, is under development by Elvesys, Inc in France. This platform will be able to offer results within 15 minutes on-site.

In addition, the study of the vaginal microbiome may identify signatures associated with a risk of maternal-fetal infection, particularly in case of PROM or PTB. Advanced sequencing technology and metagenomics will be used to characterize these signatures, and may lead to further markers to be included in the point-of-care test. Finally, biomarkers of inflammation will be detected, including IL-6 (Interleukin).

In this study, the InSPIRe platform will be compared in the laboratory to conventional microbiological and immunological detection.

Four groups of pregnant women will be recruited in prospective cohorts : uneventful pregnancies, term PROM, preterm labor and preterm PROM.

The purpose of the InSPIRe project is to improve the prevention of perinatal bacterial infections, with the novel Elvesys point of care system to rapidly detect and characterize microorganisms responsible for neonatal sepsis from a single vaginal sample.

Eligibility criteria: Inclusion Criteria:

* Pregnant woman,
* Gestational age over 22 SA,
* Patient agreeing to sign informed consent,
* Patient aged at least 18 years old,
* Patient with health insurance,
* Singleton, twin or multiple pregnancy.

Exclusion Criteria:

* Fetal death or non-viable fetus,
* maternal age under 18,
* Patient unable to express her consent,
* Patient under guardianship.

Primary outcomes:
measure: Presence of Streptococcus B
timeFrame: Day 0
measure: Presence of Streptococcus B
timeFrame: until 20 weeks
Secondary outcomes:
measure: Maternal fetal infection
timeFrame: until 20 weeks + 3 days
measure: A positive bacteriological result in the vaginal sample
timeFrame: Day 0
measure: A positive bacteriological result in the vaginal sample
timeFrame: until 20 weeks
measure: Vaginal dysmorphism
timeFrame: day 0
measure: Vaginal dysmorphism
timeFrame: until 20 weeks
measure: Antibiotic resistance
timeFrame: Day 0
measure: Antibiotic resistance
timeFrame: until 20 weeks
measure: Highlighting specific virulence markers
timeFrame: Day 0
measure: Highlighting specific virulence markers
timeFrame: until 20 weeks
measure: Maternal local biomarkers definition
timeFrame: Day 0
measure: Maternal local biomarkers definition
timeFrame: until 20 weeks
measure: Bacteriological signature definition
timeFrame: Day 0
measure: Bacteriological signature definition
timeFrame: until 20 weeks
measure: Chorioamnionitis
timeFrame: Day 0
measure: Chorioamnionitis
timeFrame: until 20 weeks
Other outcomes:
Locations:
city: Colombes
country: France
facility: Hopital Louis Mourier
city: Paris
country: France
facility: Hôpital Cochin
city: Paris
country: France
facility: Hopital Bichat
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Laurent Mandelbrot, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Assistance Publique - Hôpitaux de Paris
name: Claire Poyart, MD, PhD
role: STUDY_DIRECTOR
affiliation: Assistance Publique - Hôpitaux de Paris
name: Pierre Yves Ancel, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Joubrel C, Tazi A, Six A, Dmytruk N, Touak G, Bidet P, Raymond J, Trieu Cuot P, Fouet A, Kerneis S, Poyart C. Group B streptococcus neonatal invasive infections, France 2007-2012. Clin Microbiol Infect. 2015 Oct;21(10):910-6. doi: 10.1016/j.cmi.2015.05.039. Epub 2015 Jun 5.
citation: Dussaux C, Senat MV, Bouchghoul H, Benachi A, Mandelbrot L, Kayem G. Preterm premature rupture of membranes: is home care acceptable? J Matern Fetal Neonatal Med. 2018 Sep;31(17):2284-2292. doi: 10.1080/14767058.2017.1341482. Epub 2017 Jul 6.
citation: Kayem G, Batteux F, Girard N, Schmitz T, Willaime M, Maillard F, Jarreau PH, Goffinet F. Predictive value of vaginal IL-6 and TNFalpha bedside tests repeated until delivery for the prediction of maternal-fetal infection in cases of premature rupture of membranes. Eur J Obstet Gynecol Reprod Biol. 2017 Apr;211:8-14. doi: 10.1016/j.ejogrb.2017.01.013. Epub 2017 Jan 12.
citation: Lorthe E, Ancel PY, Torchin H, Kaminski M, Langer B, Subtil D, Sentilhes L, Arnaud C, Carbonne B, Debillon T, Delorme P, D'Ercole C, Dreyfus M, Lebeaux C, Galimard JE, Vayssiere C, Winer N, L'Helias LF, Goffinet F, Kayem G. Impact of Latency Duration on the Prognosis of Preterm Infants after Preterm Premature Rupture of Membranes at 24 to 32 Weeks' Gestation: A National Population-Based Cohort Study. J Pediatr. 2017 Mar;182:47-52.e2. doi: 10.1016/j.jpeds.2016.11.074. Epub 2017 Jan 9.
citation: Delorme P, Goffinet F, Ancel PY, Foix-L'Helias L, Langer B, Lebeaux C, Marchand LM, Zeitlin J, Ego A, Arnaud C, Vayssiere C, Lorthe E, Durrmeyer X, Sentilhes L, Subtil D, Debillon T, Winer N, Kaminski M, D'Ercole C, Dreyfus M, Carbonne B, Kayem G. Cause of Preterm Birth as a Prognostic Factor for Mortality. Obstet Gynecol. 2016 Jan;127(1):40-48. doi: 10.1097/AOG.0000000000001179.
citation: Plainvert C, El Alaoui F, Tazi A, Joubrel C, Anselem O, Ballon M, Frigo A, Branger C, Mandelbrot L, Goffinet F, Poyart C. Intrapartum group B Streptococcus screening in the labor ward by Xpert(R) GBS real-time PCR. Eur J Clin Microbiol Infect Dis. 2018 Feb;37(2):265-270. doi: 10.1007/s10096-017-3125-2. Epub 2017 Oct 29.
citation: Six A, Firon A, Plainvert C, Caplain C, Bouaboud A, Touak G, Dmytruk N, Longo M, Letourneur F, Fouet A, Trieu-Cuot P, Poyart C. Molecular Characterization of Nonhemolytic and Nonpigmented Group B Streptococci Responsible for Human Invasive Infections. J Clin Microbiol. 2016 Jan;54(1):75-82. doi: 10.1128/JCM.02177-15. Epub 2015 Oct 21.