Maternal- Fetal Infection

Neonatal Infection Clinical Trial

— InSPIRe  

Official title:

Innovative Strategies for Perinatal Infectious Risk Reduction

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03371056
• Other study ID #: K170907J
• Status: Recruiting
• Phase: N/A
• Start date: August 28, 2018
• Est. completion date: December 30, 2023

Study information

• Verified date: September 2022
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Laurent Mandelbrot, MD, PhD
• Phone: +33 1 47 60 63 39
• Email: Laurent.mandelbrot[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2600
• Est. completion date: December 30, 2023
• Est. primary completion date: August 30, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• Infections
• Neonatal Infection

Intervention

Biological:
• Bacteriological analyses on clinical samples performed with swabs
Bacteriological analyses will be performed to assess the InSPIRe kit

Locations

Country	Name	City	State
France	Hopital Louis Mourier	Colombes
France	Hopital Bichat	Paris
France	Hôpital Cochin	Paris

Sponsors (6)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Bforcure, BPIfrance, INSERM IAME UMR 1137, INSERM U1153, Institut Cochin

Country where clinical trial is conducted

France, 

References & Publications (7)

Delorme P, Goffinet F, Ancel PY, Foix-L'Hélias 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. — View 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. — View Citation

Joubrel C, Tazi A, Six A, Dmytruk N, Touak G, Bidet P, Raymond J, Trieu Cuot P, Fouet A, Kernéis 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. — View Citation

Kayem G, Batteux F, Girard N, Schmitz T, Willaime M, Maillard F, Jarreau PH, Goffinet F. Predictive value of vaginal IL-6 and TNFa 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. — View 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. — View 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® 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. — View 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. Erratum in: J Clin Microbiol. 2016 Jul;54(7):1932. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Presence of Streptococcus B		Day 0
Primary	Presence of Streptococcus B		until 20 weeks
Secondary	Maternal fetal infection	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.	until 20 weeks + 3 days
Secondary	A positive bacteriological result in the vaginal sample	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)	Day 0
Secondary	A positive bacteriological result in the vaginal sample	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)	until 20 weeks
Secondary	Vaginal dysmorphism	Defined by lactobacillus's decrease or loss in association with the spread of anaerobic flora.	day 0
Secondary	Vaginal dysmorphism	Defined by lactobacillus's decrease or loss in association with the spread of anaerobic flora.	until 20 weeks
Secondary	Antibiotic resistance	Highlighted by a resistant profile in bacteriological culture for various classes of antibiotics such as ß-lactamines, macrolides or aminoamides.	Day 0
Secondary	Antibiotic resistance	Highlighted by a resistant profile in bacteriological culture for various classes of antibiotics such as ß-lactamines, macrolides or aminoamides.	until 20 weeks
Secondary	Highlighting specific virulence markers	Like GBS clone CC17, Enterobacteriaceae that produce capsular antigen type K1. By usual molecular techniques.	Day 0
Secondary	Highlighting specific virulence markers	Like GBS clone CC17, Enterobacteriaceae that produce capsular antigen type K1. By usual molecular techniques.	until 20 weeks
Secondary	Maternal local biomarkers definition	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.	Day 0
Secondary	Maternal local biomarkers definition	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.	until 20 weeks
Secondary	Bacteriological signature definition	Presence or lack of specific bacteriological sequences detected by global sequencing and metagenomics analyses	Day 0
Secondary	Bacteriological signature definition	Presence or lack of specific bacteriological sequences detected by global sequencing and metagenomics analyses	until 20 weeks
Secondary	Chorioamnionitis	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.	Day 0
Secondary	Chorioamnionitis	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.	until 20 weeks