PLatform for Adaptive Trials In Perinatal UnitS - [Core Protocol]
NCT Number: NCT06461429
Acronym: PLATIPUS
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Preterm Birth
Interventions: DRUG: Erythromycin|DRUG: Amoxicillin and Erythromycin|DRUG: Azithromycin|DRUG: Caffeine citrate: Low dose|DRUG: Caffeine citrate: Medium dose|DRUG: Caffeine citrate: High dose
Sponsor: University of Melbourne
Collaborators: University of Auckland, New Zealand|Monash University|The University of Western Australia|La Trobe University|The University of New South Wales|University of Tasmania|Menzies School of Health Research|University of Adelaide|University of Sydney|Mater Medical Research Institute
Sex: ALL
Age: CHILD, ADULT, OLDER_ADULT
Enrollment: 100000
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2025-02-01
Completion Date: 2050-12-31

Summary:
PLATIPUS is an adaptive platform trial aimed at improving the health of infants born preterm (before 37 weeks' gestation). PLATIPUS will compare how different treatments and care provided to pregnant women and people at risk of preterm birth and infants born preterm affect infant health.

The main questions PLATIPUS aims to answer are:

1. What effect/s do different treatments/care provided to pregnant women and people at risk of preterm birth have on the health of their infants? (Pregnancy domains)
2. What effect/s do different treatments/care given to infants born preterm have on their health ? (Neonatal domains).

This registration record relates to the PLATIPUS Core (or 'master') protocol which provides guidance for the overall running of the trial. Additional appendices will outline the aims, questions, treatments, and activities for each separate research question (domain). Each Domain-Specific Appendix will be registered separately on ClinicalTrials.gov and will link to this record.

Primary Outcome Measures: Number of participants who progress by at least one level higher on the PLATIPUS Ordinal Outcome Scale, 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 Outcome Measures: Number of well liveborn infants, Well, liveborn infants who have not met the diagnostic criteria for worse scale outcomes.

The ordinal outcome scale ranks short-term neonatal outcomes associated with longer-term health in ascending severity. An infant is assigned the outcome that is the highest (worst) for which they have met diagnostic criteria at any time prior to 42 weeks PMA or first hospital discharge (whichever is earlier)., At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).|Number of infants admitted to the neonatal unit during primary hospital admission for 48 hours or more., Infants admitted to the neonatal unit during primary hospital admission for 48 hours or more., At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).|Number of infants admitted to neonatal unit during primary hospital admission for <48 hours., Infants admitted to any level of neonatal unit during the birth admission, for less than 48 hours., At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).|Number of infants who received non-invasive respiratory support or oxygen therapy for ≥ 4 hours (excluding delivery room) and less than 5 days., Infants who received non-invasive respiratory support or oxygen therapy for ≥ 4 hours (excluding delivery room) and less than 5 days., At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).|Number of infants who received non-invasive respiratory support or oxygen therapy for 5 days or more., Infants who received non-invasive respiratory support or oxygen therapy for 5 days or more., At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).|Number of infants who received mechanical ventilation via endotracheal tube for ≥ 4 hours (excluding delivery room) and <7 days., Infants who received mechanical ventilation via endotracheal tube for ≥ 4 hours (excluding delivery room) and \<7 days., At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).|Total duration of infant's first hospitalisation, in days, Total duration of infant's first hospitalisation, in days. An average of three months., From date of infant birth to date of first discharge home from hospital (or date of death, whichever occurs earlier), assessed up to 12 months.|Number of infants who received mechanical ventilation via endotracheal tube for 7 days or more., Infants who received mechanical ventilation via endotracheal tube for 7 days or more., At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).|Number of infants with moderate respiratory morbidity., Infants with a gestational age \<37 weeks who received oxygen therapy at 40 weeks' postmenstrual age., At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).|Number of infants with necrotising enterocolitis OR sepsis., A. Necrotising enterocolitis (NEC) Infants with imaging suggestive of NEC (radiograph or ultrasound) including pneumatosis intestinalis, portal venous gas, persistently dilated loop of bowel, AND broad-spectrum antibiotics for ≥7 days.

Note: any infant requiring surgery for NEC should be ranked as 'major surgery'.

OR

B. Sepsis Infants with organism isolated in blood or Cerebral Spinal Fluid (CSF) (via culture or polymerase chain reaction (PCR)) AND treatment with antimicrobials for 5 days or more., At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).|Number of infants with severe respiratory morbidity., Infants with severe respiratory morbidity defined as one or more of the following:

1. Gestational age \<37 weeks and respiratory support (HF \>2L/min, Continuous Positive Airway Pressure (CPAP), Non-Invasive Positive Pressure Ventilation (NIPPV), Nasal High Frequency Oscillatory Ventilation (nHFOV), mechanical ventilation via an endotracheal tube) for more than 24 hours at 40 weeks' postmenstrual age.
2. Discharged home with oxygen and/or respiratory support.
3. Tracheostomy., At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).|Number of participants who underwent major surgery., Infants who underwent major surgery, defined as one of the following:

1. Laparotomy
2. Thoracotomy
3. Craniotomy
4. Ligation of a ductus arteriosus
5. Required surgery for NEC.
6. Excludes inguinal hernia repair, tracheostomy, neurosurgical intervention for post hemorrhagic hydrocephalus., At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).|Any breastmilk feeding (yes/no) at 42 weeks' postmenstrual age or day of first discharge home from hospital (whichever occurs earliest), Any breastmilk feeding at 42 weeks' postmenstrual age or on day of first hospital discharge home (whichever occurs earliest). Data will be collected as yes/no., At 42 weeks' postmenstrual or on day of first discharge home from hospital (whichever occurs earliest)|Number of infants with TWO of Brain Injury OR Major Surgery OR Severe Respiratory Morbidity, who did not experience any worse scale outcomes., Infants that meet the definition of TWO of Brain Injury OR Major Surgery OR Severe Respiratory Morbidity (as defined in Scale Categories 10, 11 and 12), At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).|Number of infants with Brain injury AND Major surgery AND Severe respiratory morbidity., Infants that meet the definition of Brain Injury AND Major Surgery AND Severe Respiratory Morbidity (as defined in Scale Categories 10, 11 and 12), At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).|Number of infants with brain injury., Infants with brain injury can be diagnosed on ultrasound or magnetic resonance imaging. Brain injury includes one or more of the following:

a. Major intraventricular haemorrhage, unilateral or bilateral, defined as i. Papile Grade 3 or 4 AND/OR ii. Moderate-severe periventricular haemorrhagic infarction b. Cystic periventricular leukomalacia, unilateral or bilateral c. Moderate or severe white matter injury on MRI at near-term or term equivalent age d. Any cerebellar haemorrhage e. Other major ischaemic injury such as arterial stroke or hypoxic ischaemic injury f. Post haemorrhagic hydrocephalus requiring drainage., At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).|Number of infants who died, Death includes fetal death in utero, intrapartum stillbirth, neonatal death, and death before hospital discharge of a liveborn infant., At any time prior to 42 weeks' postmenstrual age or first hospital discharge home from hospital (whichever is earlier).|Maternal Outcome Set: Infant's birth weight z-score, Infants birth weight z-score.

This is a secondary outcome for Pregnancy Domains only., At birth|Maternal Outcome Set: Infant's gestational age at birth, Infant's gestational age at birth.

This is a secondary outcome for Pregnancy Domains only., At birth|Maternal Outcome Set: Number of maternal deaths, Death of the mother or pregnant person.

This is a secondary outcome for Pregnancy Domains only., After trial entry and within 42 days postpartum|Maternal Outcome Set: Number of participants with severe maternal morbidity Maternal Outcome Set: Severe maternal morbidity, Includes Intensive Care Unit (ICU) admission to an intensive care unit, sepsis, eclampsia, amniotic fluid embolism, pregnancy-related hysterectomy, severe primary postpartum haemorrhage, uterine rupture, cardiac arrest, mechanical ventilation (not for birth), stroke).

This is a secondary outcome for Pregnancy Domains only., After trial entry and within 42 days postpartum|Maternal Outcome Set: Length of maternal hospitalisation, in days, Number of days from trial entry to hospital discharge, in days. An average of three weeks.

This is a secondary outcome for Pregnancy Domains only., From date of trial entry to date of discharge home from hospital (or date of death, whichever occurs earlier), assessed up to 12 months.|Maternal Outcome Set: Number of participants readmitted to hospital, Readmission to hospital (any reason) after first hospital discharge and before 42 days postpartum.

This is a secondary outcome for Pregnancy Domains only., After trial entry AND after first discharge home from hospital AND within 42 days postpartum. Measured at 42 days postpartum, YES/NO and reason for re-admission.|Maternal Outcome Set: Mode of birth, Includes: vaginal birth, assisted vaginal birth, caesarean.

This is a secondary outcome for Pregnancy Domains only., At birth