A Combination of Antibiotics to Decrease Neonatal Morbidity and Mortality for Previable Threatened Labor

NCT ID: NCT06572761

Last Updated: 2024-08-27

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 350 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-30
• Study Completion Date: 2028-05-31

Brief Summary

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.

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.

Conditions

Previable Labour With Intact Membranes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Combination of antibiotics

Combination of antibiotics (3rd generation of cephalosporin, clarithromycin, metronidazole)

+ routine care (emergency cerclage, vaginal progesterone)

Group Type: EXPERIMENTAL

Combination of antibiotics

Intervention Type: DRUG

Ceftriaxone : 1g/day parenteral clarithromycin 500 mg\*2/day orally metronidazole 500mg\*3/ day orally

Emergency cerclage

Intervention Type: DEVICE

Emergency cerclage

Vaginal progesterone

Intervention Type: DRUG

Vaginal progesterone

Routine care

Routine care (emergency cerclage, vaginal progesterone)

Group Type: ACTIVE_COMPARATOR

Emergency cerclage

Intervention Type: DEVICE

Emergency cerclage

Vaginal progesterone

Intervention Type: DRUG

Vaginal progesterone

Interventions

Combination of antibiotics

Ceftriaxone : 1g/day parenteral clarithromycin 500 mg\*2/day orally metronidazole 500mg\*3/ day orally

Intervention Type: DRUG

Emergency cerclage

Emergency cerclage

Intervention Type: DEVICE

Vaginal progesterone

Vaginal progesterone

Intervention Type: DRUG

Other Intervention Names

Ceftriaxone; clarithromycin, metronidazole

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thibaud QUIBEL, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Poissy-Saint Germain

Jean BOUYER

Role: STUDY_CHAIR

Institut National de la Santé Et de la Recherche Médicale, France

Locations

Centre Hospitalier Poissy-Saint Germain

Poissy, , France

Countries

France

Central Contacts

Thibaud QUIBEL, MD, PhD

Role: CONTACT

thibaud.quibel@ght-yvelinesnord.fr

0178636012

Charly LARRIEU

Role: CONTACT

charly.larrieu@aphp.fr

01 58 41 34 78

Facility Contacts

Thibaud QUIBEL, MD, PhD

Role: primary

0178636012

Other Identifiers

2023-505500-37-00

Identifier Type: CTIS

Identifier Source: secondary_id

APHP220670

Identifier Type: -

Identifier Source: org_study_id