Which oxygen saturation level should we use for very premature infants? A randomised controlled trial

ISRCTN	ISRCTN00842661
DOI	https://doi.org/10.1186/ISRCTN00842661
Secondary identifying numbers	G0400415

Submission date: 07/02/2006
Registration date: 23/03/2006
Last edited: 08/03/2016

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Neonatal Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

Not provided at time of registration

Study website

Contact information

Dr Peter Brocklehurst
Scientific

NPEU
University of Oxford
Old Road Campus
Oxford
OX3 7LF
United Kingdom

Phone	+44 (0)1865 289719
Email	Peter.Brocklehurst@npeu.ox.ac.uk

Study information

Study design	Double-blind randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Information leaflet for parents: http://www.npeu.ox.ac.uk/boost/downloads/boost_pil.pdf
Scientific title	Which oxygen saturation level should we use for very premature infants? A randomised controlled trial
Study acronym	BOOST-II UK
Study hypothesis	Does varying the concentration of inspired oxygen so as to target a low (85-89%) versus a high (91-95%) functional arterial oxygen saturation (SpO2), from the day of birth until the baby is breathing air (or until the baby has reached a postmenstrual age of at least 36 weeks) affect the incidence of: 1. Retinopathy of prematurity (plus disease or Grade 3 and 4) and its two year outcome? 2. Other surgery (for conditions such as patent ductus arteriosus, post-haemorrhagic ventriculomegaly or necrotising enterocolitis)? 3. Chronic lung disease? 4. Death or severe neurosensory disability on assessment 2 years after the child was due to be born? 5. Poor weight gain and head growth between birth and 36 weeks postmenstrual age, and between birth and 2 years of age?
Ethics approval(s)	Trent Multi-Centre Ethics Committee, 02/05/2007, ref: 06/MRE04/91
Condition	Prematurity
Intervention	The intervention is to maintain functional oxygen saturations in the range 85-89% or 91-95%. Masimo radical oximeters (Irvine, CA) will be used to monitor oxygen saturation levels. The oximeters will be modified to display and store a figure that is either 3% above or 3% below the 'true' oxygen saturation between 85% and 95% as computed by the machines' internal algorithm. Outside of these limits the oximeter will display the true value. Staff will aim for an oximeter reading of between 88 and 92%. This will, therefore, generate two trial groups: one for which oxygen saturation is maintained at 85-89%, and one for which it is maintained at 91-95%. Added 30/11/2015: The Masimo oximeters used in the trial were revised on 08/12/2008 to correct an artefact in their calibration algorithm. Achieved oxygen saturation distributions were clearly different with the revised oximeters. On 02/11/2009 the Data Monitoring Committee recommended that the Trial Steering Committee should consider whether the data from the two oximeter types should be considered separately. On 01/12/2010, blind to any outcome data, the Trial Steering Committee recommended to the Chief Investigator to change the protocol and to enrol the originally intended target sample size of 1,200 infants using the revised oximeters and to make this the primary analysis outcome population for the trial. A secondary analysis was planned to include the results of the infants treated with the original oximeters.
Intervention type	Other
Primary outcome measure	Death or serious neurosensory disability at 2 years corrected for prematurity Added 30/11/2015: Serious neurosensory disability was defined before recruitment commenced as: a cognitive score of <70 (i.e. more than 2 standard deviations below the mean) using the Bayley Scale of Infant Development (BSID-3); severe visual loss (certifiable as legally blind or partially sighted); severe cerebral palsy (unable to walk without help at 2 years); deafness requiring (or too severe to benefit from) a hearing aid. Before the neurodevelopmental assessments even began, a cut-off score <85 on the cognitive or language component of the Bayley-III was decided because this matched a cognitive score <70 on the BSID-II that was used from the outset in some of the NeOProM trials. Bayley-III assessments could not always be arranged. To minimize the risk of bias from post-randomization exclusions, alternative corroborative measures of cognition and language were therefore pre-specified in the Statistical Analysis Plan (SAP) on 27/11/2013 and in the final version of the SAP that was signed off on 31/03/2014 prior to unblinding or analysis of the results. Serious neurosensory disability was assessed blind to trial group assessment. Paediatricians completed a follow-up assessment including information about visual function, hearing, gross motor function, the results of the Bayley-III test or any other test of cognitive function, an assessment of language skills, an assessment of the degree of any developmental delay and information about general health. Parents were asked to fill in a parental questionnaire including information about general health, strengths and difficulties and Parent Report of Children’s Abilities–Revised (PARCA-R). If a Paediatrician report could not be obtained or was incomplete the missing information was sought from the family General Practitioner (GP). Tests reported on the Paediatrician form included the Wechsler Preschool and Primary Scales of Intelligence (WPPSI-III), the Denver Developmental Screening Test, the Griffiths Mental Development Scales, and the Schedule of Growing Skills. The primary outcome of death or serious neurosensory disability was first defined by death, severe visual loss, deafness or cerebral palsy. In the remaining infants the cognitive measure of serious neurosensory disability was first defined as a cognitive or language score <85 on the Bayley-III. If this was not available the outcome was classified using the Paediatrician’s assessment of developmental delay or language delay and then by the GP assessment. Free text on the forms returned by health professionals and parents was assessed independently by two assessors masked to group assignment to adjudicate cognitive outcome in a small number of cases. A secondary analysis of the results was pre-specified, excluding the alternative measures of disability.
Secondary outcome measures	1. Respiratory outcomes: 1.1. Days of endotracheal intubation 1.2. Days of nasal continuous positive airway pressure 1.3. Supplemental oxygen at a postmenstrual age of 36 weeks 1.4. Days of oxygen prior to home discharge 1.5. Days in oxygen after home discharge 2. Retinopathy of prematurity (ROP), plus disease, stage 3 and 4 disease 3. Patent ductus arteriosus requiring medical or surgical treatment 4. Necrotising enterocolitis, Bell stage 3 or 4 5. Changes in weight and head circumference from birth to 36 weeks postmenstrual age, and 2 years after delivery was due 6. Retinal structure when last seen for ophthalmic review; outcomes at age 2 years 7. Re-admissions to hospital until 2 years after delivery was due (and their cause) 8. Cerebral palsy (and its severity) 9. Visual disability 10. Deafness 11. Developmental delay using the Bayley Test Mental Developmental Index (MDI) 12. Other disability not classifiable as neurosensory in origin 13. All postneonatal (>27 days) deaths, together with their immediate and underlying cause
Overall study start date	01/04/2005
Overall study end date	31/05/2014

Eligibility

Participant type(s)	Patient
Age group	Neonate
Sex	Both
Target number of participants	1200 (973 recruited by end of recruitment)
Participant inclusion criteria	Infants are eligible if they are: 1. Less than 28 weeks gestation at birth 2. Less than 12 h old (24 h if the baby is outborn) 3. The clinician and parents are substantially uncertain which SpO2 is better
Participant exclusion criteria	Recruitment is not appropriate if there is no realistic prospect of survival, or follow-up is unlikely to be possible
Recruitment start date	29/09/2007
Recruitment end date	24/12/2010

Locations

Countries of recruitment

England
Ireland
United Kingdom

Study participating centre

University of Oxford

Oxford
OX3 7LF
United Kingdom

Sponsor information

University of Oxford (UK)
University/education

c/o Kathryn Dally (Acting Head)
Medical Research Services Office
Medical School Office
Level 3
John Radcliffe Hospital
Headington
Oxford
OX3 9DU
England
United Kingdom

Phone	+44 (0)1865 289728
Email	Kathryn.Dally@admin.ox.ac.uk
"ROR"	https://ror.org/052gg0110

Funders

Funder type

Government

Medical Research Council (UK)
Government organisation / National government

Alternative name(s): Medical Research Council (United Kingdom), UK Medical Research Council, MRC
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	30/05/2013		Yes	No
Results article	results	25/02/2016		Yes	No

Editorial Notes

08/03/2016: Publication reference added.
On 02/12/2013 the overall trial end date was changed from 30/11/2013 to 31/05/2014.
On 06/12/2012 Ireland was added to the countries of recruitment.