For over 60 years the most appropriate oxygen level for preterm babies remains unknown. To answer this, we will combine data from over 5300 babies to be sure the expected benefits of lower oxygen for babies’ eyes and lungs does not come at the expense of increasing death or major disability in these children. Planning to do this before the results of any of the trials are known is called a prospective meta-analysis. This is the first time this technique has been used in neonatal medicine.

Official Title

Appropriate Levels of Oxygen Saturation for Extremely Preterm Infants: Prospective Individual Patient Data Meta-analysis

Conditions

  • Infant, Premature
  • Bronchopulmonary Dysplasia
  • Retinopathy of Prematurity
  • Infant, Newborn
  • Infant, Low Birth Weight

Study Type

Interventional

Study Design

Randomized, Parallel Assignment, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Treatment

Further Details

Primary Outcome Measures:

  • Composite outcome of death or major disability by 18-24 months corrected age
    [ Time Frame: by 18-24 months corrected age (gestational age plus chronological age) ] [ Designated as safety issue: Yes ]
  • Major disability defined as having any of the following:
    • cognitive score < 85 on Bayley Scales of Infant Development (BSID) III
    • severe visual loss
    • cerebral palsy with inability to walk at 2yrs
    • deafness requiring hearing aids

Secondary Outcome Measures:

  • Retinopathy of prematurity (ROP) treatment by laser photocoagulation or cryotherapy
    [ Time Frame: at 2 years corrected age ] [ Designated as safety issue: Yes ]
  • ROP treatment by laser photocoagulation or cryotherapy is performed if Type I ROP or threshold ROP occurs
  • Measures of respiratory support
    [ Time Frame: 36 weeks postmenstrual age ] [ Designated as safety issue: Yes ]
  • Measures of respiratory support, defined as (a) supplemental oxygen requirement at 36 weeks postmenstrual age, (b) days of endotracheal intubation (c) days of continuous positive airway pressure (CPAP), (d) days of supplemental oxygen, (e) days on home oxygen
  • Patent ductus arteriosus
    [ Time Frame: at 2 years corrected age ] [ Designated as safety issue: Yes ]
  • Patent ductus arteriosus diagnosed by ultrasound and requiring medical treatment
  • Patent ductus arteriosus requiring surgical treatment
    [ Time Frame: at 2 years corrected age ] [ Designated as safety issue: Yes ]
  • Necrotising enterocolitis requiring surgery
    [ Time Frame: at 2 years corrected age ] [ Designated as safety issue: Yes ]
  • Weight
    [ Time Frame: at birth, 36 weeks postmenstrual age, discharge home and 18-24 months corrected age ] [ Designated as safety issue: No ]
  • Re-admissions to hospital
    [ Time Frame: up to 18-24 months postmenstrual age ] [ Designated as safety issue: Yes ]
  • Cerebral palsy with Gross Motor Function Classification System (GMFCS) level 2 or higher or Manual Ability Classification System (MACS) level 2 or higher
    [ Time Frame: at 18-24 months corrected age ] [ Designated as safety issue: Yes ]
  • Blindness
    [ Time Frame: 2 years corrected age ] [ Designated as safety issue: Yes ]
  • Defined as <6/60 vision, 1.3 logMAR in both eyes
  • Deafness requiring hearing aids
    [ Time Frame: 2 years corrected age ] [ Designated as safety issue: Yes ]
  • Quantitative Bayley III scores
    [ Time Frame: 2 years corrected age ] [ Designated as safety issue: No ]
  • Death
    [ Time Frame: 2 years corrected age ] [ Designated as safety issue: Yes ]

 

Arms Assigned Interventions
High Oxygen saturation:
Experimental Procedure: Higher oxygen
saturation target range (91%-95%)

Higher oxygen saturation (91%-95%)
higher (SpO2 91-95%) functional oxygen saturation 
target range from birth, or soon thereafter

Lower oxygen saturation: Active Comparator 
Lower oxygen saturation (85%-89%) 
Lower (SpO2 85%-89%) functional oxygen
saturation target range from birth, or soon
thereafter

 

 

 

 

 

 

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 over 5,300 enrolled infants.

Study Start

March 2005 – April 2015

Eligibility & Criteria

  • Ages Eligible for Study: up to 24 Hours
  • Genders Eligible for Study: Both
  • Accepts Healthy Volunteers: No

Inclusion Criteria:
Infants < 28wks gestation


Exclusion Criteria:

Infants > 28wks gestation

Total Enrolment

5230

Contact Details

Lisa Askie  +61 2 9562 5000