The Centre for the Studies of Asphyxia and Resuscitation

Population

Preterm infants born at 23+0 to 28+6 weeks’ gestation

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Primary Objective

The null hypothesis for this study is that the incidence of mortality or abnormal neurodevelopmental outcomes at 24 +6 months corrected age will be no different by using either higher initial oxygen concentration of 60% compared to using lower initial oxygen concentration of 30% for resuscitation of preterm infants of 230-286 weeks’ gestation.

 

Primary Hypothesis: Population (P), Intervention (I), Comparison (C), Outcome (O), Timeline (T):  

P In preterm infants born at 23+0-28+6 weeks’ gestation  

I does initiating resuscitation with a higher oxygen concentration of 60%

C compared to initiating with a lower oxygen concentration of 30%  

O increase or decrease the incidence of mortality or the presence of major neurodevelopmental outcomes as defined by either: i) cerebral palsy with an inability to walk unassisted; ii) major developmental delay involving cognition or speech, iii) visual (cannot fixate/ legally blind, or corrected acuity <6/60 in both eyes), or hearing impairment (requiring a hearing aid or cochlear implants)

T at 24+6 months corrected age?  

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Design and Sample Size

This cluster crossover design unmasked randomized controlled trial (RCT) will compare two oxygen concentrations at initiation of resuscitation.   1250 infants – 625 control / 625 intervention  

 

Inclusion Criteria

Infants with gestational age between 23+0 to 28+6 based on best available obstetrical estimate

ii) Infants designated to receive full resuscitation, i.e., no parental request or pre-determined decision to forego resuscitation

iii) No known major congenital or chromosomal malformation

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Exclusion Criteria 

i) Infant born outside of study centres and transported to centre after delivery

ii) Parents’ refusal to give consent to this study  

 

Efficacy Endpoints 

Primary:

• Composite between 24 +6  months corrected age of all-cause mortality or the presence of a major neurodevelopmental outcome defined as any one of: (i) non-ambulatory cerebral palsy; (ii) severe cognitive delay, (iii) hearing impairment (requiring a hearing aid or cochlear implants), and (iv) visual (cannot fixate/ legally blind, or corrected acuity <6/60 in both eyes)

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Secondary: 

• Delivery room interventions

• Neonatal UTSTEIN

• All-cause in-hospital mortality

• Severe brain injury, defined as Grade 3 and 4 IVH / intraparenchymal hemorrhage or echodense intraparenchymal lesions, periventricular leukomalacia, porencephalic cysts or ventriculomegaly on cranial ultrasound

• Bronchopulmonary dysplasia

• Severe retinopathy of prematurity (stage 3 or 4 or treated cases)

• among others

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Safety Evaluations 

Adverse events

 

Statistical Methodology

Interim analyses will be conducted when 20%, 33%, and 66% participants completed primary outcome. The final analysis will be conducted after the study is completed, unblinded, and the database is released for analysis.

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Clinical Centers

Canada and Ireland

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Enrolment Period: 4 years

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ClinicalTrials.Gov Trial: ​​NCT03825835

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Published Trial protocol: https://pmc.ncbi.nlm.nih.gov/articles/PMC10996184/​