The specific trial aim is to establish whether the use of a high, dynamic 8-12 cmH2O PEEP level strategy to support the lung during stabilisation at birth, compared with a static 5-6 cmH2O PEEP level strategy, increases the rate of survival without…
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Source
Brief title
Condition
- Neonatal respiratory disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Objective
The primary objective of this study is to evaluate the impact of dynamic PEEP
on the incidence of survival without BPD in extremely preterm infants born <29
weeks PMA compared with static PEEP.
Secondary outcome
The secondary objectives of this study are to compare the rates of common
neonatal morbidities. We will capture many of the same initial DR resuscitation
details, short-term respiratory morbidity, and potential harm secondary
outcomes as the SAIL Trial[33], plus the additional secondary outcomes specific
to applied positive pressures in the DR and NICU as detailed in Section 10.2.
In particular, the principal secondary outcomes of:
* Failure of non-invasive ventilation in first 72 hours (treatment failure)
* Oxygen requirement >=50% for 3 or more consecutive hours in first 72 hours
* Surfactant therapy in the first 7 days
* Air leak and/or pulmonary interstitial emphysema (defined on chest
radiograph; CXR) in the first 10 days of life
* Patent ductus arteriosus requiring therapy in the first 72 hours
* Imaging findings of intraventricular haemorrhage (grade III-IV)
Background summary
All infants born <29 weeks* postmenstrual age (PMA) require positive
end-expiratory pressure (PEEP) at birth. PEEP is a simple, feasible and
cost-effective therapy to support extremely preterm infants that is used
globally. The effective and safe level of PEEP to use after preterm birth
remains the most important unanswered question in neonatal respiratory
medicine. We will undertake an international multicentre randomised controlled
trial to address the following question:
In extremely preterm infants, does the use of a high, dynamic PEEP level
strategy to support the lung during stabilisation (*resuscitation*) at birth,
compared with the current practice of a static PEEP level, reduce the rate of
death or bronchopulmonary dysplasia (BPD)?
This trial will address four key knowledge gaps identified in the most recent
2015 International Liaison Committee of Resuscitation (ILCOR) Neonatal
consensus statement:
* Assessing whether individualising (dynamic) PEEP is superior to static PEEP
* The uncertainty regarding applied pressure strategies to support the lung
during stabilisation at birth arising from the lack of a properly powered,
well-designed randomised trial specifically addressing important outcomes for
respiratory support in the Delivery Room (DR)
* The optimal PEEP strategy to use
* Determining the differential effects of PEEP at different gestational ages.
Study objective
The specific trial aim is to establish whether the use of a high, dynamic 8-12
cmH2O PEEP level strategy to support the lung during stabilisation at birth,
compared with a static 5-6 cmH2O PEEP level strategy, increases the rate of
survival without bronchopulmonary dysplasia (BPD) in extremely preterm infants
born <29 weeks* PMA, and reduces rates of common neonatal morbidities.
Hypothesis
We hypothesise that in preterm infants born <29 weeks PMA who receive
respiratory support during stabilisation at birth, a high, dynamic PEEP
strategy (i.e., PEEP 8-12 cmH2O individualised to clinical need) as compared to
a static PEEP of 5-6 cmH2O, will:
1. Increase survival without BPD (primary outcome); and
2. Reduce rates of common neonatal morbidities such as failure of non-invasive
respiratory support in the first 72 hours of life (secondary outcome).
Study design
This is a phase III/IV, two parallel group, non-blinded, 1:1 randomised
controlled, multi-national, multi-centre, trial comparing dynamic PEEP (dynamic
group) with standard PEEP strategy (static group).
The intervention will take place in the Delivery Room. The intervention period
will be from the time of birth until 20 minutes after birth.
The follow-up period will extend to 36 weeks PMA (primary endpoint), and 24
months corrected GA to determine important long-term neurodevelopmental and
respiratory outcomes routinely collected as part of standard neonatal follow
up, such as cognitive delay, cerebral palsy, deafness, or blindness (detailed
in Section 10.2).
Intervention
Dynamic 8-12 cmH2O PEEP level strategy to support the lung during stabilisation
at birth, compared with a static 5-6 cmH2O PEEP level strategy
Study burden and risks
The extent of burden can be classified as low as the nCPAP with PEEP is already
part of standard of care. Participating to the POLAR trial will in our opinion
have a low additional risk as prematur infants have by default already risks on
pulmonary complications. Therefore the intervention will have a relatively low
additional risk but with context specific SAE's we keep track if complications
will unexpectedly increase.
Flemington Road 50
Melbourne 3052
AU
Flemington Road 50
Melbourne 3052
AU
Listed location countries
Age
Inclusion criteria
- infant born between 23 weeks 0 days and 28 weeks 6 days PMA
- planned to receive respiratory support intervention (resuscitation) at birth
with nCPAP and or positive pressure ventilation in the delivery room to support
transition and/or respiratory failure related to pretermaturity
- the infants has a parent or other legal representative capable of
understanding the informed consent document and providing consent on the
participants behalf either orospectively or after birth and randomsation if
prenatal consent was not possible
Exclusion criteria
- infants is not planned fot active care (based on the attending clinician or
by family decision)
- infant with potential severe pulmonary hypoplasia due to PPROM or hydrops
foetalis
- major congenital anomaly's
- refused informed consent
- no guardian who can provide informed consent
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT04372953 |
| CCMO | NL77338.018.21 |