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

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

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)?

Study Overview

• Status: Completed
• Conditions: Infant, Newborn, Diseases; Infant, Premature, Diseases; Retinopathy of Prematurity; Bronchopulmonary Dysplasia; Infant, Very Low Birth Weight
• Intervention / Treatment: Procedure: Higher oxygen saturation target range (91%-95%); Procedure: Lower oxygen saturation (85%-89%)

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.

• Study Type: Interventional
• Enrollment (Actual): 4965
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Canberra, Australian Capital Territory, Australia
      • Canberra Hospital
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital Women and Babies
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital
    • New Lambton, New South Wales, Australia, 2310
      • John Hunter Hospital
    • St Leonards, New South Wales, Australia
      • Royal North Shore Hospital, NSW
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital,
  • Queensland
    • Brisbane, Queensland, Australia, 4006
      • Royal Brisbane Women's Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3052
      • Royal Women's Hospital
    • Melbourne, Victoria, Australia, 3800
      • Monash Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 day (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Infants < 28wks gestation

Exclusion Criteria:

• Infants > 28wks gestation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: High Oxygen saturation; Higher (SpO2 91-95%) functional oxygen saturation target range from birth, or soon thereafter, for durations as specified in each trial protocol.	Procedure: Higher oxygen saturation target range (91%-95%); higher (SpO2 91-95%) functional oxygen saturation target range from birth, or soon thereafter
ACTIVE_COMPARATOR: Lower oxygen saturation; Lower (SpO2 85-89%) functional oxygen saturation target range from birth, or soon thereafter, for durations as specified in each trial protocol.	Procedure: Lower oxygen saturation (85%-89%); Lower (SpO2 85%-89%)functional oxygen saturation target range from birth, or soon thereafter

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
composite outcome of death or major disability by 18-24 months corrected 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	by 18-24 months corrected age (gestational age plus chronological age)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Retinopathy of prematurity (ROP) treatment by laser photocoagulation or cryotherapy or anti-VEGF injection		at 18-24 months corrected age
measures of respiratory support	• 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).	36 weeks postmenstrual age
Patent ductus arteriosus diagnosed by ultrasound and receiving medical treatment		at 18-24 months corrected age
Patent ductus arteriosus receiving surgical treatment		at 18-24 months corrected age
Weight z-score based on WHO percentile charts (WHO Multicentre Growth Reference Study Group, 2006)		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
Re-admissions to hospital		up to 18-24 months postmenstrual age
Cerebral palsy with GMFCS level 2 or higher or MACS level 2 or higher at 18-24 months corrected age		at 18-24 months corrected age
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
deafness requiring hearing aids		at 18-24 months corrected age
Bayley-III Developmental Assessment cognitive score <85 and/or language score <85		2 years corrected age
death		at 18-24 months corrected age

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subgroup analyses will be undertaken on all pre-specified primary and secondary outcomes.	Subgroups: Gestational ageless than 26 weeksgreater than or equal to 26 weeks; Inborn or outborn; Use of any antenatal corticosteroids = yes if any of the followingincomplete, less than 24 hours before birthcompletemore than 7 days before birthstarted less than 24h before birthstarted 24h or more before birth; Male or female gender; Small for gestation agebirth weight below trialist defined cut-pointbirth weight less than 10th percentile using WHO centile charts; Multiple or singleton birth; Mode of deliveryVaginal if any of the following: vaginal, vaginal-cephalic, vaginal-breechCaesarean if any of the following: caesarean, caesarean section before onset of labour, caesarean section after onset of labour, caesarean section; Time of intervention commencementless than 6 hours after birth6 hours or more after birth; Oximeter calibration softwareoriginalrevised	at 18-24 months corrected age

Collaborators and Investigators

• Sponsor: University of Sydney
• Collaborators: University of Pennsylvania; University of California, San Diego; University of Oxford; University of Otago
• Investigators: Principal Investigator: Lisa Askie, National Health and Medical Research Council, Australia

Publications and helpful links

General Publications

• Askie LM, Brocklehurst P, Darlow BA, Finer N, Schmidt B, Tarnow-Mordi W; NeOProM Collaborative Group. NeOProM: Neonatal Oxygenation Prospective Meta-analysis Collaboration study protocol. BMC Pediatr. 2011 Jan 17;11:6. doi: 10.1186/1471-2431-11-6.
• Askie LM, Darlow BA, Finer N, Schmidt B, Stenson B, Tarnow-Mordi W, Davis PG, Carlo WA, Brocklehurst P, Davies LC, Das A, Rich W, Gantz MG, Roberts RS, Whyte RK, Costantini L, Poets C, Asztalos E, Battin M, Halliday HL, Marlow N, Tin W, King A, Juszczak E, Morley CJ, Doyle LW, Gebski V, Hunter KE, Simes RJ; Neonatal Oxygenation Prospective Meta-analysis (NeOProM) Collaboration. Association Between Oxygen Saturation Targeting and Death or Disability in Extremely Preterm Infants in the Neonatal Oxygenation Prospective Meta-analysis Collaboration. JAMA. 2018 Jun 5;319(21):2190-2201. doi: 10.1001/jama.2018.5725. Erratum In: JAMA. 2018 Jul 17;320(3):308.

Study record dates

Study Major Dates

• Study Start: March 1, 2005
• Primary Completion (ACTUAL): August 1, 2014
• Study Completion (ACTUAL): August 1, 2014

Study Registration Dates

• First Submitted: May 13, 2010
• First Submitted That Met QC Criteria: May 14, 2010
• First Posted (ESTIMATE): May 17, 2010

Study Record Updates

• Last Update Posted (ACTUAL): March 13, 2019
• Last Update Submitted That Met QC Criteria: March 11, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: pulse oximetry; preterm infant; oxygen saturation; prospective meta-analysis
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Eye Diseases; Retinal Diseases; Body Weight; Lung Injury; Ventilator-Induced Lung Injury; Infant, Premature, Diseases; Birth Weight; Retinopathy of Prematurity; Bronchopulmonary Dysplasia; Infant, Newborn, Diseases
• Other Study ID Numbers: NeOProM