A Combination of Antibiotics to Decrease Neonatal Morbidity and Mortality for Previable Threatened Labor (ECHEC-MAT)

A Combination of Antibiotics to Decrease Neonatal Mortality and Morbidity for Pregnancies Complicated With Previable Labour and Intact Membranes: a Multicenter, Open-label, Randomized and Controlled Trial

The purpose of this study is to determine whether a combination of antibiotics (cephalosporin 3rd generation, clarithromycin, metronidazole) are effective to prolong pregnancies complicated with previable threatened labour with intact membranes.

Study Overview

• Status: Not yet recruiting
• Conditions: Previable Labour With Intact Membranes
• Intervention / Treatment: Drug: Combination of antibiotics; Device: Emergency cerclage; Drug: Vaginal progesterone

Detailed Description

Observational data suggest that subclinical infectious conditions can lead to spontaneous preterm labor. 10% of births are premature, but the morbidity/mortality of premature babies is concentrated mainly among newborns born before 30 weeks of gestation or weighing less than 1500 g. The relationship to infection/inflammation and premature birth is not constant throughout pregnancy, but this infectious risk increases the earlier the gestational age of spontaneous labor is (before 30 weeks). The pathogens that have the strongest associations with premature birth are Gardnerella vaginalis, Ureaplasma urealyticum and Mycoplasma hominis, but also Streptococcus B, Escherichia coli, Klebsiella spp, or Haemophilus influenzae.

Antibiotic treatment to treat an intra-amniotic infection is considered ineffective. Indeed, the last randomized trial (Oracle 2, 2001), which studied several antibiotic regimens for threatened premature delivery with intact membranes, did not find a significant reduction in neonatal morbidity/mortality after administration of co-beta-lactam, erythromycin or the combination of both. In addition, this large trial dominates the results of the latest Cochrane meta-analysis which evaluated preventive antibiotic therapy to stop premature labor with intact membranes.

Recently, it has been showed that a new combination of antibiotics (ceftriaxone, clarithromycin and metronidazole) reduced the risk of infection and intra-amniotic inflammation in preterm labor with intact membranes. This retrospective study deserves to be confirmed by a randomized study

The investigator's goal is to study whether a new combination of antibiotics in a very limited population of pregnancies complicated by the threat of late miscarriage would make it possible to prolong pregnancies in order to improve neonatal outcomes.

• Study Type: Interventional
• Enrollment (Estimated): 350
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Thibaud QUIBEL, MD, PhD; Phone Number: 0178636012; Email: thibaud.quibel@ght-yvelinesnord.fr
• Study Contact Backup: Name: Charly LARRIEU; Phone Number: 01 58 41 34 78; Email: charly.larrieu@aphp.fr

Study Locations

• France
  • Poissy, France, 78300
    • Centre Hospitalier Poissy-Saint Germain
    • Contact: Thibaud QUIBEL, MD, PhD; Phone Number: 0178636012

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Threatened previable prelabor with intact membranes between 18weeks of gestation +0/7 and 23 weeks of gestation 6/7 SA defined on endovaginal ultrasound by a short cervix ≤10 mm, and/or protrusion of the membranes on speculum examination.
• Maternal age >18 years
• Affiliated with social security
• Correct understanding of the French language
• Singleton pregnancy
• Foetus alive at time of inclusion
• Absence of regular and painful uterine contractions

Exclusion Criteria:

• Premature labor defined by regular, painful uterine contractions and a short cervix
• Protected person (patient under guardianship/curatorship/or legal protection)
• Multiple pregnancies
• Premature rupture of membranes
• Acute chorioamnionitis
• Contraindication to protocol antibiotics
• Chromosomal abnormality, congenital malformation
• Patients who received antibiotics before randomization, or requiring antibiotics for another indication (chorioamnionitis, pyelonephritis, etc.)
• Participation in another research (Specify the category: RIPH, EC, IC, etc.) or being in the exclusion period following previous research involving humans, if applicable
• Patient under AME (if no exemption from affiliation)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combination of antibiotics; Combination of antibiotics (3rd generation of cephalosporin, clarithromycin, metronidazole) + routine care (emergency cerclage, vaginal progesterone)	Drug: Combination of antibiotics; Ceftriaxone : 1g/day parenteral clarithromycin 500 mg*2/day orally metronidazole 500mg*3/ day orally; Other Names: Ceftriaxone; clarithromycin, metronidazole; Device: Emergency cerclage; Emergency cerclage; Drug: Vaginal progesterone; Vaginal progesterone
Active Comparator: Routine care; Routine care (emergency cerclage, vaginal progesterone)	Device: Emergency cerclage; Emergency cerclage; Drug: Vaginal progesterone; Vaginal progesterone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A perinatal composite outcome	Late miscarriage; Perinatal mortality; Bronchodysplasia,; Sepsis proven by blood culture,; Intraventricular hemorrhage ≥3,; Periventricular leukomalacia ≥2,; Ulcero-necrotizing enterocolitis at stage ≥2 according to the Bell classification.	Up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gestationnal age at delivery	Gestationnal age at delivery ≥ 24 weeks of gestation (wg) 0/7, 28 wg0/7, 32 wg0/7, 34 wg0/7 et 37 wg0/7; Latency period between randomisation and delivery (≥2 days, ≥7 days, ≥14 days et ≥28 days)	6 months
Maternal Morbidty	Chorioamniotitis, postpartum endometritis , sepsis proven par positive hemocultures	6 months
Bacteriological	Acquisition of multi-resistant germs during childbirth	6 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: URC-CIC Paris Descartes Necker Cochin
• Investigators: Principal Investigator: Thibaud QUIBEL, MD, PhD, Centre Hospitalier Poissy-Saint Germain; Study Chair: Jean BOUYER, Institut National de la Santé Et de la Recherche Médicale, France

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): May 1, 2030
• Study Completion (Estimated): May 1, 2030

Study Registration Dates

• First Submitted: August 23, 2024
• First Submitted That Met QC Criteria: August 23, 2024
• First Posted (Actual): August 27, 2024

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: preterm; previable labour
• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Premature Birth; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Imidazoles; Amides; Macrolides; Lactones; beta-Lactams; Lactams; Cephalosporins; Thiazines; Nitroimidazoles; Nitro Compounds; Erythromycin; Polyketides; Cefotaxime; Cephacetrile; Ceftriaxone; Metronidazole; Clarithromycin
• Other Study ID Numbers: APHP220670; 2023-505500-37-00 (Ctis)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No