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Maternal- Fetal Infection (InSPIRe)

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ClinicalTrials.gov Identifier: NCT03371056
Recruitment Status : Not yet recruiting
First Posted : December 13, 2017
Last Update Posted : August 28, 2018
Sponsor:
Collaborators:
Elvesys
BPIfrance
INSERM U1153
Institut Cochin
INSERM IAME UMR 1137
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

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.

Condition or disease Intervention/treatment Phase
Neonatal Infection Biological: Bacteriological analyses on clinical samples performed with swabs Not Applicable

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2500 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: There are 4 pre-specified groups
Masking: None (Open Label)
Primary Purpose: Screening
Official Title: Innovative Strategies for Perinatal Infectious Risk Reduction
Estimated Study Start Date : August 27, 2018
Estimated Primary Completion Date : June 30, 2022
Estimated Study Completion Date : December 30, 2022

Arm Intervention/treatment
Experimental: Woman at low risk of infection
Women with systematic vaginal sample for detection of GBS will be included.
Biological: Bacteriological analyses on clinical samples performed with swabs
Bacteriological analyses will be performed to assess the InSPIRe kit

Experimental: Woman with high risk of infection > 37 SA
Women with premature rupture of membranes (> 12 hours before labor) but > 37 SA will be included.
Biological: Bacteriological analyses on clinical samples performed with swabs
Bacteriological analyses will be performed to assess the InSPIRe kit

Experimental: Women with premature rupture of membranes (<37SA)
Woman with high risk of infection <37SA
Biological: Bacteriological analyses on clinical samples performed with swabs
Bacteriological analyses will be performed to assess the InSPIRe kit

Experimental: Women with premature delivery or premature delivery threat
Woman with high risk of infection <37SA and Women with premature delivery or premature delivery threat
Biological: Bacteriological analyses on clinical samples performed with swabs
Bacteriological analyses will be performed to assess the InSPIRe kit




Primary Outcome Measures :
  1. Presence of Streptococcus B [ Time Frame: Day 0 ]
  2. Presence of Streptococcus B [ Time Frame: until 20 weeks ]

Secondary Outcome Measures :
  1. Maternal fetal infection [ Time Frame: until 20 weeks + 3 days ]
    Infection is proved if at least a sample, generally sterile, is positive to a germ in association with a positive clinical, biological or radiologic sign of infection such as C-reactive protein or chest radiography.

  2. A positive bacteriological result in the vaginal sample [ Time Frame: Day 0 ]

    A positive result is defined as the presence of one of the subsequent germ in the bacteriological culture:

    • Escherichia coli (E. coli)
    • Streptococcus pneumoniae,
    • Group A Streptococcus
    • Haemophilus ssp (influenzae, parainfluenzae)
    • Staphylococcus aureus
    • Streptococcus milleri group
    • Enterococcus faecalis
    • Other Gram-negative bacilli type enterobacteria (Klebsiella pneumonia, Proteus mirabilis)
    • Anaerobics (Prevotella sp, bacteroid fragilis)

  3. A positive bacteriological result in the vaginal sample [ Time Frame: until 20 weeks ]

    A positive result is defined as the presence of one of the subsequent germ in the bacteriological culture:

    • Escherichia coli (E. coli)
    • Streptococcus pneumoniae,
    • Group A Streptococcus
    • Haemophilus ssp (influenzae, parainfluenzae)
    • Staphylococcus aureus
    • Streptococcus milleri group
    • Enterococcus faecalis
    • Other Gram-negative bacilli type enterobacteria (Klebsiella pneumonia, Proteus mirabilis)
    • Anaerobics (Prevotella sp, bacteroid fragilis)

  4. Vaginal dysmorphism [ Time Frame: day 0 ]
    Defined by lactobacillus's decrease or loss in association with the spread of anaerobic flora.

  5. Vaginal dysmorphism [ Time Frame: until 20 weeks ]
    Defined by lactobacillus's decrease or loss in association with the spread of anaerobic flora.

  6. Antibiotic resistance [ Time Frame: Day 0 ]
    Highlighted by a resistant profile in bacteriological culture for various classes of antibiotics such as β-lactamines, macrolides or aminoamides.

  7. Antibiotic resistance [ Time Frame: until 20 weeks ]
    Highlighted by a resistant profile in bacteriological culture for various classes of antibiotics such as β-lactamines, macrolides or aminoamides.

  8. Highlighting specific virulence markers [ Time Frame: Day 0 ]
    Like GBS clone CC17, Enterobacteriaceae that produce capsular antigen type K1. By usual molecular techniques.

  9. Highlighting specific virulence markers [ Time Frame: until 20 weeks ]
    Like GBS clone CC17, Enterobacteriaceae that produce capsular antigen type K1. By usual molecular techniques.

  10. Maternal local biomarkers definition [ Time Frame: Day 0 ]
    Presence or lack of RNA sequences and/or human specific protein detected by RT-PCR or ELISA-PCR depending on the presence or lack of a proved or suspected maternal fetal infection.

  11. Maternal local biomarkers definition [ Time Frame: until 20 weeks ]
    Presence or lack of RNA sequences and/or human specific protein detected by RT-PCR or ELISA-PCR depending on the presence or lack of a proved or suspected maternal fetal infection.

  12. Bacteriological signature definition [ Time Frame: Day 0 ]
    Presence or lack of specific bacteriological sequences detected by global sequencing and metagenomics analyses

  13. Bacteriological signature definition [ Time Frame: until 20 weeks ]
    Presence or lack of specific bacteriological sequences detected by global sequencing and metagenomics analyses

  14. Chorioamnionitis [ Time Frame: Day 0 ]

    Clinical or paraclinical factors associated with risk of chorioamnionitis or maternal fetal infection such as prematurity, clinical signs (maternal fever, fetal tachycardia, increase in C-reactive protein, hyperleukocytosis, pus-like amniotic fluid) , oligohydramnios (defined by the greatest cistern < 25 mm); increase in pro-calcitonin in umbilical cord ok histological signs of placental inflammation.

    Clinical chorioamnionitis is defined as a maternal fever> 39° (in one shot) with no other cause or >38°(confirmed) in association with abnormal fetal heartbeat (>160/min exceeding 10 min), maternal hyperleukocytosis (>15000/mm3 without corticotherapy) or pus-like amniotic fluid.

    Histological chorioamnionitis is defined by the presence of neutrophil polynuclears in amnion or chorion in association with the presence of neutrophil polynuclears in umbilical cord blood vessels.


  15. Chorioamnionitis [ Time Frame: until 20 weeks ]

    Clinical or paraclinical factors associated with risk of chorioamnionitis or maternal fetal infection such as prematurity, clinical signs (maternal fever, fetal tachycardia, increase in C-reactive protein, hyperleukocytosis, pus-like amniotic fluid) , oligohydramnios (defined by the greatest cistern < 25 mm); increase in pro-calcitonin in umbilical cord ok histological signs of placental inflammation.

    Clinical chorioamnionitis is defined as a maternal fever> 39° (in one shot) with no other cause or >38°(confirmed) in association with abnormal fetal heartbeat (>160/min exceeding 10 min), maternal hyperleukocytosis (>15000/mm3 without corticotherapy) or pus-like amniotic fluid.

    Histological chorioamnionitis is defined by the presence of neutrophil polynuclears in amnion or chorion in association with the presence of neutrophil polynuclears in umbilical cord blood vessels.




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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03371056


Contacts
Contact: Laurent Mandelbrot, MD, PhD 1 47 60 63 39 ext +33 Laurent.mandelbrot@aphp.fr
Contact: Laurence Lecomte, PhD 1 58 41 35 45 ext +33 laurence.lecomte@aphp.fr

Locations
France
Hopital Louis Mourier Not yet recruiting
Colombes, France, 92700
Contact: Laurent Mandelbrot, MD, PhD    1 47 60 63 39 ext +33    Laurent.mandelbrot@aphp.fr   
Hôpital Cochin Not yet recruiting
Paris, France, 75014
Contact: François Goffinet, MD, PhD    1 58 41 37 98 ext + 33    francois.goffinet@aphp.fr   
Hopital Bichat Not yet recruiting
Paris, France, 75018
Contact: Dominique Luton, MD PhD    1.40.25.76.83 ext +33    dluton@free.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Elvesys
BPIfrance
INSERM U1153
Institut Cochin
INSERM IAME UMR 1137
Investigators
Principal Investigator: Laurent Mandelbrot, MD, PhD Assistance Publique - Hôpitaux de Paris
Study Director: Claire Poyart, MD, PhD Assistance Publique - Hôpitaux de Paris
Study Director: Pierre Yves Ancel, MD, PhD Assistance Publique - Hôpitaux de Paris

Publications:

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03371056     History of Changes
Other Study ID Numbers: K170907J
First Posted: December 13, 2017    Key Record Dates
Last Update Posted: August 28, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Neonatal infections
maternal-fetal infection
group B streptococcus
vaginal sample
antibiotic prophylaxis
bacterial resistance

Additional relevant MeSH terms:
Infection
Communicable Diseases