An interventional study of Erythromycin 250mg + placebo and Azithromycin 500mg + placebo in PPROM and Preterm, sponsored by University of Melbourne. Not yet recruiting. Open to female participants. Per ClinicalTrials.gov, last updated 2025-04-02.
Sponsored by University of Melbourne · Not applicable, Interventional, and Prevention
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).
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:
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.
75 studies on the registry are indexed under Preterm Premature Rupture of the Membranes; 17 are open to participants now.
This study's planned enrollment of 3,900 is above the median of 95 across 49 interventional studies indexed under Preterm Premature Rupture of the Membranes.
Browse Preterm Premature Rupture of the Membranes studies →University of Melbourne is the lead sponsor of 86 studies on the registry; 22 are open to participants now.
Counted across the registry records on this site, refreshed daily.
PLATFORM ELIGIBILITY
Participants must meet all core PLATIPUS platform inclusion criteria:
Participants will be excluded from participation if they meet any core PLATIPUS platform exclusion criteria:
Pregnant women and people who meet ALL of the core platform inclusion criteria and none of the exclusion criteria will be considered for PROMOAT-specific eligibility.
PROMOAT-SPECIFIC ELIGIBILITY
Platform-eligible participants must meet all PROMOAT-specific inclusion criteria:
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:
Participants will be excluded from participation if they meet core PLATIPUS platform exclusion criteria:
Participants will be excluded from participation if they meet any PROMOAT-specific exclusion criteria:
Platform-eligible participants who meet all PROMOAT-specific inclusion criteria and none of the PROMOAT-specific exclusion criteria will be eligible to participate in PROMOAT.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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 daily for 7 days. Oral preparation only. Placebo tablets instead of penicillin for blinding purposes.
Drug: Azithromycin 500mg + placebo
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
Antibiotic.
Antibiotic.
Drug page: Erythromycin
Antibiotics.
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.
Time frame: At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).]
Time (randomisation) to birth
Number of days from randomisation to birth.
Time frame: From randomisation to birth
Estimated antepartum/intrapartum/postpartum (< 24 hours) blood loss
Estimated antepartum/intrapartum/postpartum (\<24 hours of birth) blood loss.
Time frame: Less than 24 hours of birth.
Rate of clinical chorioamnionitis
Clinical chorioamnionitis Clinical suspicion of intra-amniotic infection such as: maternal fever (\>/= 38C AND 2 of maternal tachycardia (\> 100 beats/min), fetal tachycardia 26,27(\> 160 beats/min), uterine tenderness, purulent/malodorous amniotic fluid, maternal leukocytosis (white blood cell count \>/= 15,000/mm3) AND Antibiotics commenced for treatment for clinically suspected chorioamnionitis.
Time frame: To birth.
Rate of histological chorioamnionitis/funisitis
Histological chorioamnionitis/funisitis • Presence of inflammation in the placenta, chorion, umbilical cord and/or amnion with or without fetal inflammatory response defined according to staging of maternal (MIR) or fetal inflammatory response (FIR).
Time frame: To birth
Rate of puerperal infection
Puerperal infection Infection of the maternal genital tract, urinary tract and wound infection from birth to day 42 postpartum AND Antibiotic treatment commenced
Time frame: From birth to day 42 postpartum
Rate of early onset neonatal sepsis
Isolation of a bacterial or fungal organism from at least one of blood or CSF culture or by PCR sampled within 48 hours of birth AND after consideration of clinical and laboratory evidence, a decision is made to give the infant antibiotics with therapeutic intent against this organism for \>5 days
Time frame: Within 48 hours of birth.
Duration of neonatal antibiotic use commenced within 48 hours of birth.
Duration of neonatal antibiotic treatment commenced within 48 hours of birth.
Time frame: Within 48 hours of birth.
Number of days of maternal antibiotic prescription after birth to day 42 postpartum
Estimated cumulative days of maternal antibiotic use from birth to day 42 postpartum
Time frame: From birth to Day 42 postpartum
Core Secondary Outcome 1: Number of maternal deaths within 42 days postpartum
Number of mother (or birth parent) deaths within 42 days of birth.
Time frame: From birth to 42 days postpartum
Core Secondary Outcome 2: Rate of severe maternal morbidity
Maternal or pregnant person morbidity is defined as: unplanned ICU admission, sepsis, eclampsia, amniotic fluid embolism, pregnancy-related hysterectomy, severe primary postpartum haemorrhage, uterine rupture, cardiac arrest, mechanical ventilation (not for birth), stroke.
Time frame: From platform entry to 42 days postpartum
Core Secondary Outcome 3: Duration of hospitalisation
Duration of maternal or pregnant person hospitalisation, in days, after platform entry
Time frame: From date of platform entry to date of first discharge home from hospital (birth admission).
Core Secondary Outcome 4: Rate of readmission to hospital
Rate of readmission to hospital, after first discharge home from hospital, within 42 days postpartum.
Time frame: From first discharge home from hospital (birth admission) to 42 days postpartum.
Core Secondary Outcome 5: Rate of mode of birth
Rates of vaginal birth vs assisted vaginal birth vs caesarean birth.
Time frame: At birth
Core Secondary Outcome 6: Infant gestational age at birth.
Calculated infant gestation age based on estimated date of delivery and date of birth.
Time frame: From estimated date of delivery to date of birth.
Core Secondary Outcome 7: Infant birth weight z-score.
Z-score generated from infant weight at birth and gestational age at birth.
Time frame: At birth
No study locations are listed for this record.
Plan to share: Yes — Data sharing will align with PLATIPUS (NCT06461429) policy. Version 1, Apr-2024 Once data unblinding no longer compromises the integrity of the trial, a de-identified data set collected for the analysis of domains within PLATIPUS will be made available. Conditions All domains in which the participant is co-enrolled are closed to recruitment* (*Where one or more domains in which a participant is co-enrolled are not yet closed to recruitment, the participant's data may be provided, without the treatment code, to prevent unblinding in unfinished domains). Primary domain conclusions/analyses have been published, AND The 2-year follow-up of participants within the domain/s of interest is/are complete. Supporting materials (Core Protocol, Domain-Specific Appendices, Data Dictionaries and Domain-Specific Statistical Analysis Plans) will be available. Contact: University of Melbourne - info@platipustrial.org.
Supporting information: Study protocol, Statistical analysis plan
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.
No publications or documents are linked to this record.
Start is estimated for Sep 2025; primary completion for Dec 2029, 51 months later.
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This study is not yet recruiting, as verified in Feb 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Erythromycin
Preterm Premature Rupture of the Membranes →
University of Melbourne