PLatform for Adaptive Trials In Perinatal UnitS - [Core Protocol] (PLATIPUS)

University of Melbourne

Status: Not yet enrolling

Conditions: Preterm Birth

Treatments: Drug: Caffeine citrate 30 mg/kg load and 15 mg/kg daily maintenance.; Drug: Amoxicillin and Erythromycin; Drug: Azithromycin; Drug: Caffeine citrate 40 mg/kg load and 20 mg/kg daily maintenance; Drug: Erythromycin; Drug: Caffeine citrate 20 mg/kg load and 10 mg/kg daily maintenance.

Study type: Interventional

Funder types: Other

Identifiers

NCT06461429

P-CORE-01

Details and patient eligibility

About

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.

Full 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:

Enrollment: 100,000 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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100,000 participants in 2 patient groups

Pregnancy Domain 01 - PROMOAT: Preterm Rupture Of Membranes Optimal Antibiotics Trial

Experimental group

Description:

ClinicalTrial.gov Trial Registration: NCT06906757. Population: Pregnant women and people with PPROM \<37 weeks' gestation and active neonatal management anticipated. Interventions: Randomised to receive routinely used broad-spectrum antibiotic prophylaxis

Treatment:

Drug: Erythromycin

Drug: Azithromycin

Drug: Amoxicillin and Erythromycin

Neonatal Domain 01 - BabyCCINO: Caffeine Citrate to Improve Neonatal Outcomes

Experimental group

Description:

ClinicalTrial.gov Trial Registration: NCT06972849. Population: Very preterm infants born \<32 weeks' gestation, up to 10 days old, with any clinical indication to commence caffeine treatment (any of: prevention of apnoea, treatment of apnoea, or with the aim of improving longer-term outcomes. Interventions: Randomised to receive high, medium and low-dose caffeine citrate.

Treatment:

Drug: Caffeine citrate 20 mg/kg load and 10 mg/kg daily maintenance.

Drug: Caffeine citrate 40 mg/kg load and 20 mg/kg daily maintenance

Drug: Caffeine citrate 30 mg/kg load and 15 mg/kg daily maintenance.