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Appropriate Oxygen Levels for Extremely Preterm Infants: a Prospective Meta-analysis

Not Applicable
Completed
Conditions
Infant, Newborn, Diseases
Infant, Premature, Diseases
Bronchopulmonary Dysplasia
Retinopathy of Prematurity
Infant, Very Low Birth Weight
Interventions
Procedure: Higher oxygen saturation target range (91%-95%)
Procedure: Lower oxygen saturation (85%-89%)
Registration Number
NCT01124331
Lead Sponsor
University of Sydney
Brief Summary

The primary question to be addressed by this study is: compared with a functional oxygen saturation level (SpO2) of 91-95%, does targeting SpO2 85-89% in extremely preterm infants from birth or soon after, result in a difference in mortality or major disability in survivors by 2 years corrected age (defined as gestational age plus chronological age)?

Detailed Description

Oxygen has been used in the care of small and sick newborn babies for over 60 years. However, to date there has been no reliable evidence to guide clinicians regarding what is the best level to target oxygen saturation in preterm infants to balance the four competing risks of mortality, lung disease, eye damage and developmental disability.

Five high quality randomised controlled trials are now underway assessing two different levels of oxygen saturation targeting (USA - SUPPORT; Australia - BOOST II; New Zealand - BOOST NZ; UK - BOOST II UK; Canada - COT). The value of these gold-standard trials can be further enhanced when, with careful planning, they are synthesised into a prospective meta-analysis (PMA). A PMA is one where trials are identified for inclusion in the analysis before any of the individual results are known.

We have established the Neonatal Oxygenation Prospective Meta-analysis (NeOProM) Collaboration, comprising the investigators of these five trials and a methodology team. The trials are sufficiently similar with respect to design, participants and intervention and, with planning, will have enough common outcome measures to enable their results to be prospectively meta-analysed. Together they have a combined sample size of almost 5000 enrolled infants.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
4965
Inclusion Criteria
  • Infants < 28wks gestation
Exclusion Criteria
  • Infants > 28wks gestation

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
High Oxygen saturationHigher oxygen saturation target range (91%-95%)Higher (SpO2 91-95%) functional oxygen saturation target range from birth, or soon thereafter, for durations as specified in each trial protocol.
Lower oxygen saturationLower oxygen saturation (85%-89%)Lower (SpO2 85-89%) functional oxygen saturation target range from birth, or soon thereafter, for durations as specified in each trial protocol.
Primary Outcome Measures
NameTimeMethod
composite outcome of death or major disability by 18-24 months corrected ageby 18-24 months corrected age (gestational age plus chronological age)

Major disability is defined as any of the following:

* Bayley-III Developmental Assessment cognitive score \<85 and/or language score \<85

* Severe visual loss

* Cerebral palsy with Gross Motor Function Classification System (GMFCS) level 2 or higher or Manual Ability Classification System (MACS) level 2 or higher at 18-24 months postmenstrual age

* Deafness requiring hearing aids

Secondary Outcome Measures
NameTimeMethod
Re-admissions to hospitalup to 18-24 months postmenstrual age
deafness requiring hearing aidsat 18-24 months corrected age
Retinopathy of prematurity (ROP) treatment by laser photocoagulation or cryotherapy or anti-VEGF injectionat 18-24 months corrected age
deathat 18-24 months corrected age
measures of respiratory support36 weeks postmenstrual age

• Measures of respiratory support, including the following separate outcomes a. supplemental oxygen requirement at 36 weeks postmenstrual age, b. postmenstrual age ceased endotracheal intubation, c. postmenstrual age ceased continuous positive airway pressure (CPAP), d. postmenstrual age ceased supplemental oxygen, e. postmenstrual age ceased home oxygen (if received).

Patent ductus arteriosus diagnosed by ultrasound and receiving medical treatmentat 18-24 months corrected age
Patent ductus arteriosus receiving surgical treatmentat 18-24 months corrected age
Weight z-score based on WHO percentile charts (WHO Multicentre Growth Reference Study Group, 2006)at 36 weeks' postmenstrual age and discharge home
Severe visual impairment (cannot fixate or is legally blind:<6/60 vision , 1.3 logMAR in both eyes or equivalent as defined by trial)at 18-24 months corrected age
Cerebral palsy with GMFCS level 2 or higher or MACS level 2 or higher at 18-24 months corrected ageat 18-24 months corrected age
Bayley-III Developmental Assessment cognitive score <85 and/or language score <852 years corrected age

Trial Locations

Locations (9)

Liverpool Hospital

🇦🇺

Liverpool, New South Wales, Australia

Royal Prince Alfred Hospital Women and Babies

🇦🇺

Camperdown, New South Wales, Australia

John Hunter Hospital

🇦🇺

New Lambton, New South Wales, Australia

Royal North Shore Hospital, NSW

🇦🇺

St Leonards, New South Wales, Australia

Westmead Hospital,

🇦🇺

Westmead, New South Wales, Australia

Royal Women's Hospital

🇦🇺

Melbourne, Victoria, Australia

Royal Brisbane Women's Hospital

🇦🇺

Brisbane, Queensland, Australia

Monash Medical Centre

🇦🇺

Melbourne, Victoria, Australia

Canberra Hospital

🇦🇺

Canberra, Australian Capital Territory, Australia

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