Preterm Rupture of Membranes Optimising Antibiotics Trial

NCT ID: NCT06906757

Last Updated: 2025-04-02

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 3900 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-30
• Study Completion Date: 2050-12-31

Brief Summary

The goal of this clinical trial is to learn which antibiotic regimen works best to prevent infection in pregnant women whose waters break early (preterm, pre-labour rupture of membranes, or PPROM) and assess the health outcomes of babies born to pregnant women who have received these antibiotics.

PROMOAT aims to answer the question: Which antibiotic or combined antibiotic regimen most effectively prevents infection in pregnant women with PPROM < 37+0 weeks' gestation.

Researchers will compare three antibiotic regimens already used in clinical practice to prevent infection in pregnant women with PPROM.

Participants will be randomly allocated to the antibiotic regimen they will follow for seven days, or until birth (whichever is earlier). All antibiotics will be taken orally.

Neonatal health outcomes will be collected at 42 weeks postmenstrual age and maternal birth and postpartum care outcomes assessed at 42 days postpartum.

Questionnaires will capture maternal mood at time of consent and at 42 days postpartum. Antibiotic tolerance will be assessed at the time antibiotic treatment is ceased.

This trial will be undertaken as part of the PLATIPUS trial (NCT06461429).

Detailed Description

PROMOAT aims to determine which of the most common antibiotic regimens are most effective in preventing infection in pregnant people with PPROM to improve health outcomes for their infants. PROMOAT is a pregnancy domain within the PLATIPUS adaptive platform trial (NCT06461429).

Preterm prelabour rupture of membranes (PPROM) precedes 30-40% of spontaneous preterm births and is an important cause of maternal and neonatal infection. Membrane rupture provides an entry point for microbes from the vagina to ascend into the uterine cavity, exposing the mother and the fetus to infectious pathogens leading to poor maternal and neonatal outcomes. Mothers with PPROM are at increased risk of haemorrhage, hysterectomy, sepsis, intensive care admission and death. Preterm infants exposed to in-utero infection are at higher risk of poor short- and long-term outcomes, including neonatal sepsis, neurodevelopmental delay, cerebral palsy, chronic lung disease and death.

Neonatal sepsis is the third most common cause of newborn deaths (~340,000 per year) and prevention is a major research priority, Neonatal sepsis due to pathogens acquired after PPROM may present in the first days of life and result in bacteraemia, pneumonia and meningitis. The most common pathogens associated with early-onset neonatal sepsis are Streptococcus agalactiae (aka Group B Streptococcus: GBS), Escherichia coli and Ureaplasma sp. Mortality is highest in the most immature infants, with a 54% case fatality rate in infants born before 24 weeks' gestation.

The goal in managing pregnancies complicated by PPROM is to prolong the pregnancy to enable fetal maturity without an increased risk of infection (acquired while the fetus remains in utero). Antibiotic prophylaxis has been shown to increase latency to birth but there is limited evidence to guide antibiotic choice to prevent infection in PPROM.

In PROMOAT, pregnant women with PPROM will be randomly assigned to receive one of the three intervention arms:

• Erythromycin
• Azithromycin, or
• Erythromycin and Amoxicillin.

Health outcomes will be assessed using the PLATIPUS Ordinal Outcome Scale, at 42 weeks' postmenstrual age or discharge home, whichever is earliest.

A short questionnaire at Day 7 (or birth, whichever is earlier) will measure compliance and antibiotic tolerance. A maternal and family health questionnaire will be collected at Day 42 postpartum.

Conditions

PPROM; Preterm

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Erythromycin 250mg + placebo

Erythromycin 250mg, four times a day, for 7 days. Oral preparation only.

Placebo tablets instead of penicillin for blinding purposes.

Group Type: ACTIVE_COMPARATOR

Erythromycin 250mg + placebo

Intervention Type: DRUG

Antibiotic.

Azithromycin 500mg + placebo

Azithromycin 500mg daily for 7 days. Oral preparation only.

Placebo tablets instead of penicillin for blinding purposes.

Group Type: ACTIVE_COMPARATOR

Azithromycin 500mg + placebo

Intervention Type: DRUG

Antibiotic.

Erythromycin 250mg and Amoxicillin 500mg

Erythromycin 250mg, four times a day AND Amoxicillin 500mg three times a day, for 7 days. Oral preparations only.

Group Type: ACTIVE_COMPARATOR

Erythromycin 250mg and Amoxicillin 500mg

Intervention Type: DRUG

Antibiotics.

Interventions

Erythromycin 250mg + placebo

Antibiotic.

Intervention Type: DRUG

Azithromycin 500mg + placebo

Antibiotic.

Intervention Type: DRUG

Erythromycin 250mg and Amoxicillin 500mg

Antibiotics.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Considered to be at risk of birth before 37 weeks gestation (spontaneous and provider-initiated)
• Receiving pregnancy care at a participating site (hospital) at the time of eligibility assessment and
• Meet eligibility criteria for one or more platform domains.

PROMOAT-SPECIFIC ELIGIBILITY

1. Women with singleton or multiple pregnancies complicated by preterm prelabour rupture of membranes (PPROM) < 37+0 weeks' gestation as determined by the treating clinician and standard criteria:

• Maternal history consistent with loss of fluid per vagina
• Evidence of a pool of fluid in the vagina on sterile speculum examination
• +/- positive testing for IGFBP-1 (Actim PROM) or PAMG-1 (Amnisure) AND

2. Are eligible for at least two treatment arms within the domain

3. The fetus/fetuses are alive at randomisation

4. The pregnancy is continuing and active neonatal management is planned.

Exclusion Criteria

• Inability to consent for themselves
• Perinatal death is deemed to be imminent and inevitable during the next 24 hours (at time of screening).

• Inability to consent for themselves OR
• Perinatal death is deemed to be imminent and inevitable during the next 24 hours (at time of screening).

1. Antibiotic treatment for > 24 hours administered with the aim of preventing infection from PPROM

2. Suspected maternal or fetal infection (chorioamnionitis)

3. Maternal or fetal indication for immediate birth

4. Established preterm labour (cervical dilatation ≥ 3cm AND regular contractions)

5. No appropriate antibiotic available within domain intervention arms due to allergy, contraindications, drug interactions, drug availability, or previous history of antibiotic-resistant infection/s

6. Women with a previous infant affected by GBS sepsis

7. Major congenital fetal anomaly.

• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of Melbourne

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clare Whitehead, MBChB, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Melbourne and Royal Women's Hospital (Melbourne)

Central Contacts

Clare Whitehead, MBChB, PhD

Role: CONTACT

clarew@unimelb.edu.au

00610383452000

Kelly Fredell

Role: CONTACT

info@platipustrial.org

0061432975273

Other Identifiers

P-P01-PROMOAT

Identifier Type: -

Identifier Source: org_study_id