Clinical trial NCT00718705: Reduction of Spontaneous Prematurity by Antibiotic Treatment (Josamycin)
Official title: Reduction of Spontaneous Prematurity: Impact of Antibiotic Treatment (Josamycin) in Case of Positive PCR for Ureaplasma Spp and/or Mycoplasma Hominis in Amniotic Fluid
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prematurity
Keywords: Prematurity
Ureaplasma spp
Mycoplasma Hominis
Amniotic fluid
Josamycine
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2008-07-21
Enrollment: 3200
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to test the effectiveness of an antibiotic treatment (Josamycin) in the case of positive PCR for Ureaplasma spp. and/or Mycoplasma hominis in the second quarter on the risk of premature birth.

Detailed description: Infection would be the cause of 40 % of spontaneous premature deliveries. The physiopathological hypothesis accepted is a premature ascent of present bacteria in the low genital ways towards the decidual, the foetal membranes then the amniotic liquid. These bacteria are responsible for an inflammatory reaction to the interface feto-maternal characterized by the production of proinflammatory cytokines and pro-contractants agents (prostaglandins, oxytocin) by the decidual and the membranes.

These mediators cause uterine contractions, a maturation of the uterine collar, a rupture of the membranes then a premature birth.

Several recent publications show on the one hand that Mycoplasma hominis and Ureaplasma spp. are the bacteria most frequently found in the amniotic liquid in the second quarter of the pregnancy and that a positive PCR for these bacteria is associated with a premature birth.

A probable assumption would be that Mycoplasma hominis or Ureaplasma spp. cause a premature birth by infecting the fetal membranes and the decidual, then activating the immune system and the pro-inflammatory production of cytokines. These bacteria are sensitive to antibiotic treatment.

Nevertheless, no randomized controlled trials have been carried out to determine wether an antibiotic treatment would decrease spontaneous prematurity in the case of positive PCR in the amniotic liquid.

Eligibility criteria: Inclusion Criteria:

* Patient older ≥ 18 years
* French speaking
* Women who have an amniocentesis between 15 and 20 weeks of amenorrhoea for an antenatal diagnosis
* Affiliated to social security or an equivalent system
* Karyotype analysis and ultrasound morphological normal (apart from minor signs of trisomy 21)
* Clear amniotic fluid (not contaminated by the mother's blood)
* Gestational age is between 15 WA(day+0) and 20 WA(day+6)
* Patient have not allergy to macrolides
* Do not have cure underway by macrolide
* Patient followed during her pregnancy in an investigator site
* Informed consent and signed

Exclusion Criteria:

* No speaking french
* Having an allergy to macrolides
* Having a multiple pregnancy
* Morphological Anomaly
* Patient no consented
* Lactose Intolerance
* Not agreed to participate

Primary outcomes:
measure: Premature birth
timeFrame: between 22 and 37 completed weeks of pregnancy.
Secondary outcomes:
measure: Antenatal :occurence of a miscarriage late
timeFrame: between 16 and 22 weeks of amenorrhoea
measure: Antenatal : premature delivery
timeFrame: at week of amenorrhea <= 34, 32, 28
measure: Antenatal : hospitalisation for risk of premature delivery
timeFrame: antenatal period
measure: antenatal : Number of day of hospitalisation for risk of premature delivery
timeFrame: antenatal period
measure: Antenatal : premature rupture of membranes
timeFrame: before 37 week of amenorrhea
measure: Antenatal : occurence of chorioamnionitis defined by 2 of the following criteria :maternal temperature > 38°C, uterine contractions, Fetid leucorrhoeas, foetal tachycardia > 160bpm, C reactive protein >10mg/l
timeFrame: antenatal period
measure: During childbirth : Hyperthermia > 38°C
timeFrame: Childbirth period
measure: During childbirth : fetal tachycardia > 160 bpm
timeFrame: childbirth period
measure: Post-partum : Hyperthermia > 38°C for more than 24hours
timeFrame: post partum period
measure: Post partum :need an antibiotic treatment for more than 48 hours
timeFrame: post partum period
measure: Neonatal : neonatal mortality late
timeFrame: from day 7 to day 28
measure: Neonatal : early neonatal mortality
timeFrame: from day 0 to day 6
measure: Neonatal morbidity : immediate neonatal state
timeFrame: neonatal period
measure: Neonatal morbidity : infection
timeFrame: neonatal period
measure: Neonatal morbidity : respiratory disease
timeFrame: neonatal period
measure: Neonatal morbidity : digestive disease
timeFrame: neonatal period
Other outcomes:
Locations:
city: Creteil
country: France
facility: Groupe Hospitalier Chenevier-Mondor, CHI
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Gilles KAYEM
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kayem G, Doloy A, Schmitz T, Chitrit Y, Bouhanna P, Carbonne B, Jouannic JM, Mandelbrot L, Benachi A, Azria E, Maillard F, Fenollar F, Poyart C, Bebear C, Goffinet F. Antibiotics for amniotic-fluid colonization by Ureaplasma and/or Mycoplasma spp. to prevent preterm birth: A randomized trial. PLoS One. 2018 Nov 7;13(11):e0206290. doi: 10.1371/journal.pone.0206290. eCollection 2018.