Azithromycin and Ampicillin for Late PPROM

NCT07183462 | Recruiting Phase 4

• 2 other identifiers: SHEBA-05-1755-24-NG-CTILMOH_2025-04-30_014029
• Study Type: interventional
• Target: 311
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn whether adding azithromycin to the standard antibiotic treatment (ampicillin) improves newborn outcomes in women with preterm premature rupture of membranes (PPROM) between 34.0 and 36.6 weeks of pregnancy. The main question it aims to answer is: Does the combination of ampicillin and azithromycin lower the risk of serious neonatal health problems compared to ampicillin alone? Researchers will compare two antibiotic regimens: Ampicillin alone, which is the current standard care Ampicillin with azithromycin, a broader regimen that may better prevent infections and prolong pregnancy Participants will: Receive one of the two antibiotic treatments during hospitalization. Be monitored until delivery for signs of infection and labor All participants will stay in the hospital until delivery. The study also looks at how the antibiotic choice may affect the time between membrane rupture and delivery, maternal infections, and the need for neonatal intensive care.

Conditions

Pregnancy Complications, Infectious; Premature Birth; Neonatal Diseases and Abnormalities; Antibiotic Prophylaxis; Latency Period; Prematurity

Outcome Measures

Primary Outcomes (1)

• A composite of neonatal adverse outcomes

  A composite of neonatal adverse outcomes defined as the occurrence of one or more of the following events within 72 hours after birth: use of continuous positive airway pressure (CPAP) or high-flow nasal cannula, supplemental oxygen with a fraction of inspired oxygen (FiO2) ≥0.30 for ≥4 continuous hours, extracorporeal membrane oxygenation (ECMO), mechanical ventilation, neonatal sepsis (defined as positive blood culture), hypoglycemia requiring treatment, hyperbilirubinemia requiring phototherapy, stillbirth, or neonatal death within 72 hours after delivery The composite will be reported as the number of infants who experience at least one of the listed adverse outcomes. Unit of Measure: Number of infants with ≥1 adverse outcome

  From the time of birth until 72 hours postpartum

Secondary Outcomes (34)

• Number of Infants With Severe Respiratory Morbidity

  From delivery through neonatal hospitalization or up to 28 days of life, whichever comes first.

• Number of Infants Requiring Resuscitation at Birth

  At birth

• Number of Infants Diagnosed With Respiratory Distress Syndrome

  From delivery through neonatal hospitalization or up to 28 days of life, whichever comes first

• Number of Infants Receiving Surfactant Therapy

  From delivery through neonatal hospitalization or up to 28 days of life, whichever comes first.

• Number of Infants Diagnosed With Transient Tachypnea of the Newborn

  Within first 72 hours after birth

Study Arms (2)

Standard antibiotic regimen (Ampicillin and Amoxicillin)

ACTIVE COMPARATOR

Participants in the control arm receive the standard antibiotic regimen for late PPROM, consisting of intravenous Ampicillin 2g every 6 hours for 48 hours, followed by oral Amoxicillin 500mg every 8 hours for 5 days, administered according to current clinical guidelines

Drug: Ampicillin/Amoxicillin plus single-dose PO Azithromycin

Intervention Arm - Standard Antibiotics with Azithromycin

EXPERIMENTAL

Participants in this arm will receive the standard antibiotic regimen of intravenous Ampicillin followed by oral Amoxicillin, plus a single dose of 1 gram oral Azithromycin

Drug: Intravenous Ampicillin followed by Oral Amoxicillin

Interventions

Ampicillin/Amoxicillin plus single-dose PO Azithromycin DRUG

This intervention includes intravenous Ampicillin 2 grams every 6 hours for 48 hours, followed by oral Amoxicillin 500 mg every 8 hours for 5 days, plus a single dose of oral Azithromycin 1 gram administered once at the start of treatment

Standard antibiotic regimen (Ampicillin and Amoxicillin)

Intravenous Ampicillin followed by Oral Amoxicillin DRUG

This intervention consists of intravenous Ampicillin 2 grams every 6 hours for 48 hours, followed by oral Amoxicillin 500 mg every 8 hours for 5 days

Intervention Arm - Standard Antibiotics with Azithromycin

Eligibility Criteria

• Age: 18 Years - 50 Years
• Gender Eligibility Details: Eligibility is based on biological sex (female) and pregnancy status with PPROM between 34.0 and 36.6 weeks of gestation, irrespective of the participant's gender identity
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Maternal age 18-50
• Premature rupture of membranes
• Gestational age 34.0 and 36.4 weeks
• Singleton pregnancy

You may not qualify if:

• Multiple gestations
• Individuals in active labor (defined as 3 cm dilatation and 80% effacement or more. or regular uterine construction of more than 4 in 10 minutes)
• Meconium stain amniotic fluid
• Non-reassuring fetal heart rate or status
• Maternal or fetal indication for labor:
• Suspected Chorioamnionitis
• Suspected placental abruption
• Any maternal morbidity requiring labor
• Cervical cerclage in place.
• Major fetal malformation or known chromosomal abnormalities.
• Stillbirth.
• Sensitivity to Macrolides Antibiotics

Sponsors & Collaborators

• Sheba Medical Center: lead

Study Sites (1)

Sheba medical center

Ramat Gan, Israel, Israel

RECRUITING

MeSH Terms

Conditions

Pregnancy Complications, Infectious; Premature Birth; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Interventions

Ampicillin; Amoxicillin

Condition Hierarchy (Ancestors)

Infections; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Obstetric Labor, Premature; Obstetric Labor Complications

Intervention Hierarchy (Ancestors)

Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Noa Gonen, MD

  Sheba Medical Center

  STUDY CHAIR

Central Study Contacts

Noa Gonen, MD

CONTACT

972-54-3955584; gonen.noa7@gmail.com

Michal Fishel - Bartal, MD

CONTACT

972-52-8087034; michalbartal@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Participants are randomly assigned to one of two groups. One group receives the standard antibiotic regimen, while the other group receives the standard regimen plus a single dose of intravenous Azithromycin. Both groups are followed concurrently to compare outcomes.

Study Record Dates

• First Submitted: June 4, 2025
• First Posted: September 19, 2025
• Study Start: September 10, 2025
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): July 31, 2029
• Last Updated: December 18, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)