NCT06461429

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

Platform for Adaptive Trials in Perinatal Units (Core Protocol)

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 100,000 (estimated)
• Sponsor: University of Melbourne · Academic / Other
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

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:

Conditions

• Preterm Birth

Interventions

Type	Name	Description
DRUG	Erythromycin	Antibiotic. Standard of care. Antibiotics will be administered for 7 days or until delivery (whichever is sooner).
DRUG	Amoxicillin and Erythromycin	Antibiotic. Antibiotics will be administered for 7 days or until delivery (whichever is sooner).
DRUG	Azithromycin	Antibiotic. Antibiotics will be administered for 7 days or until delivery (whichever is sooner).
DRUG	Caffeine citrate 20 mg/kg load and 10 mg/kg daily maintenance.	Lower dose caffeine: 20mg/kg load and 10mg/kg/day maintenance. Standard of care. Caffeine will be administered until at least 34+0 weeks' post-menstrual age, with the aim to cease caffeine by 36+0 weeks' post-menstrual age. Caffeine use beyond 36+0 weeks' post-menstrual age will be open-label.
DRUG	Caffeine citrate 30 mg/kg load and 15 mg/kg daily maintenance.	Medium dose caffeine: 30mg/kg load and 15 mg/kg/day maintenance. Caffeine will be administered until at least 34+0 weeks' post-menstrual age, with the aim to cease caffeine by 36+0 weeks' post-menstrual age. Caffeine use beyond 36+0 weeks' post-menstrual age will be open-label.
DRUG	Caffeine citrate 40 mg/kg load and 20 mg/kg daily maintenance	Higher dose caffeine: 40mg/kg load and 20mg/kg/day maintenance. Caffeine will be administered until at least 34+0 weeks' post-menstrual age, with the aim to cease caffeine by 36+0 weeks' post-menstrual age. Caffeine use beyond 36+0 weeks' post-menstrual age will be open-label.

Timeline

• Start date: 2025-11-01
• Primary completion: 2050-12-31
• Completion: 2050-12-31
• First posted: 2024-06-17
• Last updated: 2025-06-13