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

NCT06461429 | Not Yet Recruiting DMC

• 1 other identifier: P-CORE-01
• Study Type: interventional
• Target: 100,000
• Locations: 0 countries
• Sites: N/A

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. 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. 2.What effect/s do different treatments/care given to infants born preterm have on their health ? (Neonatal domains).

Conditions

Preterm Birth

Keywords

Preterm infant; Pregnancy; Neonatal complications; Preterm labor

Outcome Measures

Primary Outcomes (1)

• 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 for ≥ 4 hours \& \< 5 days; 5= Non-invasive respiratory support \>/= 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 Outcomes (27)

• Number of well liveborn infants

  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.

  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.

  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 positive pressure respiratory support 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 positive pressure respiratory support for 5 days or more.

  At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier).

Study Arms (2)

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

EXPERIMENTAL

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

Drug: Erythromycin; Drug: Amoxicillin and Erythromycin; Drug: Azithromycin

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

EXPERIMENTAL

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.

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

Interventions

Erythromycin DRUG

Antibiotic. Standard of care. Antibiotics will be administered for 7 days or until delivery (whichever is sooner).

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

Amoxicillin and Erythromycin DRUG

Antibiotic. Antibiotics will be administered for 7 days or until delivery (whichever is sooner).

Also known as: Amoxycillin

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

Azithromycin DRUG

Antibiotic. Antibiotics will be administered for 7 days or until delivery (whichever is sooner).

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

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

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.

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

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

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.

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

Caffeine citrate 40 mg/kg load and 20 mg/kg daily maintenance DRUG

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.

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

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may not qualify if:

• CORE PLATFORM ELIGIBILITY - PREGNANCY DOMAINS
• Pregnant and at risk of preterm birth
• Receiving care at a participating site at the time of eligibility assessment.
• Meets the eligibility criteria for at least one domain.
• 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
• Inability to consent, unless a waiver of consent has been deemed appropriate at domain-level.
• CORE PLATFORM ELIGIBILITY - NEONATAL DOMAINS
• Born preterm (\<37 weeks' gestational age)
• Receiving care at a participating site at the time of eligibility assessment.
• Meet the eligibility criteria for at least one domain.
• 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
• 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.

Sponsors & Collaborators

• University of Melbourne: lead
• University of Auckland, New Zealand: collaborator
• Monash University: collaborator
• The University of Western Australia: collaborator
• La Trobe University: collaborator
• The University of New South Wales: collaborator
• University of Tasmania: collaborator
• Menzies School of Health Research: collaborator
• University of Adelaide: collaborator
• University of Sydney: collaborator
• Mater Medical Research Institute: collaborator

Related Publications (1)

• Manley BJ, McKinlay CJD, Lee KJ, Groom KM, Whitehead CL. Adapt to survive and thrive: the time is now for adaptive platform trials for preterm birth. Lancet Child Adolesc Health. 2025 Feb;9(2):131-137. doi: 10.1016/S2352-4642(24)00328-6.

  PMID: 39855752 DERIVED

MeSH Terms

Conditions

Premature Birth; Obstetric Labor, Premature

Interventions

Erythromycin; Amoxicillin; Azithromycin; caffeine citrate

Condition Hierarchy (Ancestors)

Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Polyketides; Lactones; Organic Chemicals; Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Clare Whitehead, MBChB, PhD

  University of Melbourne, Royal Women's Hospital, Melbourne.

  PRINCIPAL INVESTIGATOR

• Brett Manley, MBBS, PhD

  University of Melbourne, Royal Women's Hospital, Melbourne

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clare Whitehead, MBChB, PhD

CONTACT

+61; clarew@unimelb.edu.au

Kelly Fredell

CONTACT

+61432975273; kelly.fredell@unimelb.edu.au

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The default position is that domains run on the PLATIPUS platform will be randomisation provided on a blinded basis. Blinding, however, may not always be feasible for some interventions and this will be specified in the related Domain-Specific protocol.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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'.

Study Record Dates

• First Submitted: May 2, 2024
• First Posted: June 17, 2024
• Study Start: November 1, 2025
• Primary Completion (Estimated): December 31, 2050
• Study Completion (Estimated): December 31, 2050
• Last Updated: June 13, 2025

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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.