Clinical trial NCT06461429: PLatform for Adaptive Trials In Perinatal UnitS - [Core Protocol]
Official title: Platform for Adaptive Trials in Perinatal Units (Core Protocol)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Preterm Birth
Keywords: Preterm infant
Pregnancy
Neonatal complications
Preterm labor
Lead sponsor: University of Melbourne
Sponsor class: OTHER
Collaborators: name: University of Auckland, New Zealand
name: Monash University
name: The University of Western Australia
name: La Trobe University
name: The University of New South Wales
name: University of Tasmania
name: Menzies School of Health Research
name: University of Adelaide
name: University of Sydney
name: Mater Medical Research Institute
First posted: 2024-06-17
Enrollment: 100000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: PLATIPUS is an Adaptive Platform Trial. Multiple interventions will be tested in this adaptive platform trial and each will be described in domain-specific platform appendices. Pregnant women and people at risk of preterm birth will participate in 'Pregnancy Domains'. Infants born preterm will participate in 'Neonatal Domains'.
Primary purpose: TREATMENT

Brief 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.

Detailed description: PLATIPUS is a multi-domain, multi-centre international adaptive platform trial and innovative approach to perinatal research.

Preterm birth (birth before 37 weeks' gestation) is a global issue. More than 15 million babies (1 in 10) are born preterm each year. Complications of preterm birth are the leading cause of death and disability among children under five years of age. These contribute to increased risk of all-cause mortality and early death from cardiovascular disease, diabetes and chronic lung disease in later life. There is no single cause of, or pathway to, preterm birth. Treatments during pregnancy aim to prevent or treat complications that can lead to preterm birth in pregnant women and people or reduce the impact of prematurity on neonatal outcomes. Treatments in the neonatal period (period shortly after birth) aim to improve survival and reduce potential morbidities in the preterm infant.

PLATIPUS will initially assess interventions given to pregnant women and people during pregnancy (Participant Group 1) and to preterm infants (Participant Group 2) in the first few days of life. Participants will be randomly allocated to all relevant domains for which they are eligible and provide consent. Using a trial-developed Ordinal Outcome Scale, the effect of pregnancy and/or neonatal interventions on neonatal outcome will be assessed at 42 weeks' post-menstrual age OR at primary hospital discharge, whichever occurs earliest. Secondary outcomes will examine the effect of interventions on individual pregnancy and/or neonatal endpoints, and may be domain-specific. All pregnancy domains will include a 'Maternal Outcome Set' to assess maternal health and intervention safety.

In contrast to conventional clinical trials, PLATIPUS has been designed to examine multiple different treatment options at once within the same platform. Both pregnant and neonatal participants will be randomly assigned to different concurrent treatment options, with an initial focus on treatments already considered as part of clinical care. As the trial advances, novel interventions may also be included. Interventions will be evaluated within domains. A domain is defined as a set of interventions that are intended for a specific health problem or specific therapeutic option.

Bayesian adaptive statistical modelling will be used to evaluate treatment efficacy at regular interim adaptive analyses of the pre-specified outcomes for each intervention in each domain. This will allow determination of the effectiveness of interventions once sufficient data has been accrued, rather than when a pre-specified sample size is reached. Adaptive analyses will compute the posterior probabilities of superiority, futility, inferiority, or equivalence for pre-specified comparisons within domains. Each of these potential conclusions will be pre-defined prior to commencing the intervention domain. Decisions about trial results (e.g., concluding superiority or equivalence) will be based on pre-specified threshold values for posterior probability.

All trial procedures are outlined in the "core" protocol described in this registration. Separate domain protocols with information specific to each intervention included in PLATIPUS will be linked to this registration at separate clinicaltrials.gov records:

Eligibility criteria: Potential participants with core platform eligibility AND who meet all domain-specific inclusion criteria and none of the domain-specific exclusion criteria for at least one PLATIPUS domain, will be eligible to 'enrol' in the PLATIPUS trial and randomised to all eligible domains, for which consent has been provided.

CORE PLATFORM ELIGIBILITY - PREGNANCY DOMAINS

Inclusion Criteria: Pregnant women and people must fulfil the following inclusion criteria to be eligible to participate in PLATIPUS:

1. Pregnant and at risk of preterm birth
2. Receiving care at a participating site at the time of eligibility assessment.
3. Meets the eligibility criteria for at least one domain.

Exclusion Criteria: Pregnant women and people who meet the following criteria will be excluded from participation in this trial:

1. Circumstances where death (pregnant woman or person/fetal) is deemed to be imminent and inevitable. The treating team may however decide that providing an opportunity for the pregnant woman or person to participate would be in their and/or their fetus/infant's interest. OR
2. Inability to consent, unless a waiver of consent has been deemed appropriate at domain-level.

CORE PLATFORM ELIGIBILITY - NEONATAL DOMAINS

Inclusion Criteria: Preterm infants must fulfil the following criteria to be eligible to participate in PLATIPUS, infants must be:

1. Born preterm (\<37 weeks' gestational age)
2. Receiving care at a participating site at the time of eligibility assessment.
3. Meet the eligibility criteria for at least one domain.

Exclusion Criteria: Preterm infants who meet the following criteria will be excluded from participation in this trial:

1. Circumstances where death (neonatal) is deemed to be imminent and inevitable. The treating team may however decide that providing an opportunity for the infant to participate is in the infant's interest. OR
2. Parental/guardian inability to consent, unless a waiver of consent has been deemed appropriate at domain-level.

DOMAIN-SPECIFIC ELIGIBILITY CRITERIA

Potential participants who meet core platform eligibility criteria will be assessed for eligibility to participate in trial domains available at their hospital. Domain-specific eligibility criteria are outlined in the related Domain-Specific Appendices.

Primary outcomes:
measure: Number of participants who progress by at least one level higher on the PLATIPUS Ordinal Outcome Scale
timeFrame: At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).
Secondary outcomes:
measure: Number of well liveborn infants
timeFrame: At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).
measure: Number of infants admitted to the neonatal unit during primary hospital admission for 48 hours or more.
timeFrame: At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).
measure: Number of infants admitted to neonatal unit during primary hospital admission for <48 hours.
timeFrame: At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).
measure: Number of infants who received non-invasive positive pressure respiratory support for ≥ 4 hours (excluding delivery room) and less than 5 days.
timeFrame: At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).
measure: Number of infants who received non-invasive positive pressure respiratory support for 5 days or more.
timeFrame: At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).
measure: Number of infants who received mechanical ventilation via endotracheal tube for ≥ 4 hours (excluding delivery room) and <7 days.
timeFrame: At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).
measure: Number of infants who received mechanical ventilation via endotracheal tube for 7 days or more.
timeFrame: At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).
measure: Number of infants with moderate respiratory morbidity.
timeFrame: At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).
measure: Number of infants with necrotising enterocolitis OR sepsis.
timeFrame: At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).
measure: Number of infants with severe respiratory morbidity.
timeFrame: At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).
measure: Number of participants who underwent major surgery.
timeFrame: At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).
measure: Number of infants with brain injury.
timeFrame: At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).
measure: Number of infants with TWO of Brain Injury OR Major Surgery OR Severe Respiratory Morbidity, who did not experience any worse scale outcomes.
timeFrame: At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).
measure: Number of infants with Brain injury AND Major surgery AND Severe respiratory morbidity.
timeFrame: At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).
measure: Number of infants who died
timeFrame: At any time prior to 42 weeks' postmenstrual age or first hospital discharge home from hospital (whichever is earlier).
measure: Total duration of infant's first hospitalisation, in days
timeFrame: 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.
measure: Any breastmilk feeding (yes/no) at 42 weeks' postmenstrual age or day of first discharge home from hospital (whichever occurs earliest)
timeFrame: At 42 weeks' postmenstrual age or on day of first discharge home from hospital (whichever occurs earliest)
measure: Number of infants with diagnosed patent ductus arteriosus (PDA)
timeFrame: At 42 weeks' postmenstrual age or on day of first discharge home from hospital (whichever occurs earliest)
measure: Number of infants diagnosed with retinopathy of prematurity (ROP)
timeFrame: At 42 weeks' postmenstrual age or on day of first discharge home from hospital (whichever occurs earliest)
measure: Number of infants who received postnatal corticosteroids
timeFrame: From date of trial entry to 42 weeks postmenstrual age or discharge home from hospital (whichever is earliest)
measure: Maternal Outcome Set: Infant's birth weight z-score
timeFrame: At birth
measure: Maternal Outcome Set: Infant's gestational age at birth
timeFrame: At birth
measure: Maternal Outcome Set: Number of maternal deaths
timeFrame: After trial entry and within 42 days postpartum
measure: Maternal Outcome Set: Number of participants with severe maternal morbidity Maternal Outcome Set: Severe maternal morbidity
timeFrame: After trial entry and within 42 days postpartum
measure: Maternal Outcome Set: Length of maternal hospitalisation, in days
timeFrame: From date of trial entry to date of discharge home from hospital (or date of death, whichever occurs earlier), assessed up to 12 months.
measure: Maternal Outcome Set: Number of participants readmitted to hospital
timeFrame: 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.
measure: Maternal Outcome Set: Mode of birth
timeFrame: At birth
Other outcomes:
Locations:
Study officials:
affiliation: University of Melbourne, Royal Women's Hospital, Melbourne.
name: Clare Whitehead, MBChB, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Melbourne, Royal Women's Hospital, Melbourne
name: Brett Manley, MBBS, PhD
role: PRINCIPAL_INVESTIGATOR
References: