Reduction of Spontaneous Prematurity by Antibiotic Treatment (Josamycin) (PREMYC)

Reduction of Spontaneous Prematurity: Impact of Antibiotic Treatment (Josamycin) in Case of Positive PCR for Ureaplasma Spp and/or Mycoplasma Hominis in Amniotic Fluid

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.

Study Overview

• Status: Completed
• Conditions: Prematurity
• Intervention / Treatment: Drug: Josamycin; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 3200
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Creteil, France, 94
    • Groupe Hospitalier Chenevier-Mondor, CHI

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2; Placebo	Drug: Placebo; Placebo with posology of 2 grams per day by oral way during 10 days
Experimental: 1; josamycin	Drug: Josamycin; josamycin with posology of 2 grams per day by oral way during 10 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Premature birth	between 22 and 37 completed weeks of pregnancy.

Secondary Outcome Measures

Outcome Measure	Time Frame
Antenatal :occurence of a miscarriage late	between 16 and 22 weeks of amenorrhoea
Antenatal : premature delivery	at week of amenorrhea <= 34, 32, 28
Antenatal : hospitalisation for risk of premature delivery	antenatal period
antenatal : Number of day of hospitalisation for risk of premature delivery	antenatal period
Antenatal : premature rupture of membranes	before 37 week of amenorrhea
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	antenatal period
During childbirth : Hyperthermia > 38°C	Childbirth period
During childbirth : fetal tachycardia > 160 bpm	childbirth period
Post-partum : Hyperthermia > 38°C for more than 24hours	post partum period
Post partum :need an antibiotic treatment for more than 48 hours	post partum period
Neonatal : neonatal mortality late	from day 7 to day 28
Neonatal : early neonatal mortality	from day 0 to day 6
Neonatal morbidity : immediate neonatal state	neonatal period
Neonatal morbidity : infection	neonatal period
Neonatal morbidity : respiratory disease	neonatal period
Neonatal morbidity : digestive disease	neonatal period

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Bayer
• Investigators: Principal Investigator: Gilles KAYEM, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: July 17, 2008
• First Submitted That Met QC Criteria: July 18, 2008
• First Posted (Estimate): July 21, 2008

Study Record Updates

• Last Update Posted (Estimate): December 29, 2011
• Last Update Submitted That Met QC Criteria: December 27, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: Prematurity; Ureaplasma spp; Mycoplasma Hominis; Amniotic fluid; Josamycine
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth; Anti-Infective Agents; Anti-Bacterial Agents; Josamycin
• Other Study ID Numbers: P060216