Preterm Rupture of Membranes Optimising Antibiotics Trial

NCT06906757 | Not Yet Recruiting DMC

• 1 other identifier: P-P01-PROMOAT
• Study Type: interventional
• Target: 3,900
• Locations: 0 countries
• Sites: N/A

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).

Conditions

PPROM; Preterm

Keywords

Pregnancy, Preterm, PPROM, Antibiotics; chorioamnionitis

Outcome Measures

Primary Outcomes (1)

• Number of participants who progress by at least one level higher on the PLATIPUS Ordinal Outcome Scale [PLATIPUS Core Primary Outcome]

  The PLATIPUS-Ordinal Outcome Scale ranks the most severe core short-term infant health outcome in the specified time frame. Levels 1-15: 1= Well, liveborn infant; 2= Neonatal unit admission for \<48 hours; 3= Neonatal unit admission for \>/= 48 hours; 4= Non-invasive respiratory support or oxygen therapy for ≥ 4 hours \& \< 5 days; 5= Non-invasive respiratory support or oxygen therapy \>/= 5 days; 6= Mechanical ventilation via endotracheal tube for ≥ 4 hours \& \<7 days; 7= Mechanical ventilation via endotracheal tube for \>/=7 days; 8= Moderate respiratory morbidity; 9=Necrotising enterocolitis AND/OR Sepsis; 10= Severe Respiratory Morbidity; 11= Major Surgery; 12= Brain Injury; 13= TWO of severe respiratory morbidity OR major surgery OR brain injury; 14= Severe respiratory morbidity \& major surgery \& brain injury; 15 = Death.

  At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).]

Secondary Outcomes (8)

• Time (randomisation) to birth

  From randomisation to birth

• Estimated antepartum/intrapartum/postpartum (< 24 hours) blood loss

  Less than 24 hours of birth.

• Rate of clinical chorioamnionitis

  To birth.

• Rate of histological chorioamnionitis/funisitis

  To birth

• Rate of puerperal infection

  From birth to day 42 postpartum

Other Outcomes (7)

• Core Secondary Outcome 1: Number of maternal deaths within 42 days postpartum

  From birth to 42 days postpartum

• Core Secondary Outcome 2: Rate of severe maternal morbidity

  From platform entry to 42 days postpartum

• Core Secondary Outcome 3: Duration of hospitalisation

  From date of platform entry to date of first discharge home from hospital (birth admission).

Study Arms (3)

Erythromycin 250mg + placebo

ACTIVE COMPARATOR

Erythromycin 250mg, four times a day, for 7 days. Oral preparation only. Placebo tablets instead of penicillin for blinding purposes.

Drug: Erythromycin 250mg + placebo

Azithromycin 500mg + placebo

ACTIVE COMPARATOR

Azithromycin 500mg daily for 7 days. Oral preparation only. Placebo tablets instead of penicillin for blinding purposes.

Drug: Azithromycin 500mg + placebo

Erythromycin 250mg and Amoxicillin 500mg

ACTIVE COMPARATOR

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

Drug: Erythromycin 250mg and Amoxicillin 500mg

Interventions

Erythromycin 250mg + placebo DRUG

Antibiotic.

Erythromycin 250mg + placebo

Azithromycin 500mg + placebo DRUG

Antibiotic.

Azithromycin 500mg + placebo

Erythromycin 250mg and Amoxicillin 500mg DRUG

Antibiotics.

Erythromycin 250mg and Amoxicillin 500mg

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Inability to consent for themselves
• Perinatal death is deemed to be imminent and inevitable during the next 24 hours (at time of screening).
• PROMOAT-SPECIFIC ELIGIBILITY
• 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
• Are eligible for at least two treatment arms within the domain
• The fetus/fetuses are alive at randomisation
• The pregnancy is continuing and active neonatal management is planned.
• Inability to consent for themselves OR
• Perinatal death is deemed to be imminent and inevitable during the next 24 hours (at time of screening).
• Antibiotic treatment for \> 24 hours administered with the aim of preventing infection from PPROM
• Suspected maternal or fetal infection (chorioamnionitis)
• Maternal or fetal indication for immediate birth

Sponsors & Collaborators

• University of Melbourne: lead

MeSH Terms

Conditions

Preterm Premature Rupture of the Membranes; Premature Birth; Chorioamnionitis

Interventions

Erythromycin; Azithromycin; Amoxicillin

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Fetal Diseases; Fetal Membranes, Premature Rupture; Placenta Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

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

Study Officials

• Clare Whitehead, MBChB, PhD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clare Whitehead, MBChB, PhD

CONTACT

00610383452000; clarew@unimelb.edu.au

Kelly Fredell

CONTACT

0061432975273; info@platipustrial.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All parties will be blinded to the assigned intervention.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: PROMOAT is a domain within the PLATIPUS adaptive platform trial (NCT06461429).

Study Record Dates

• First Submitted: February 18, 2025
• First Posted: April 2, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2050
• Last Updated: April 2, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: This is estimated to be approximately six months following the completion of the two-year follow-up of domain participants.
• Access Criteria: To be determined. Access requests will be subject to review by trial subcommittees. The Trial Steering Committee will approve or disapprove requests. A Data Transfer Agreement and Authorship Agreement signed by relevant parties and evidence of ethical approval will be required.