Plain English Summary
Not provided at time of registration
Study website
Contact information
Type
Scientific
Contact name
Dr Peter Brocklehurst
ORCID ID
Contact details
NPEU
University of Oxford
Old Road Campus
Oxford
OX3 7LF
United Kingdom
+44 (0)1865 289719
Peter.Brocklehurst@npeu.ox.ac.uk
Additional identifiers
EudraCT/CTIS number
IRAS number
ClinicalTrials.gov number
Protocol/serial number
G0400415
Study information
Scientific title
Which oxygen saturation level should we use for very premature infants? A randomised controlled trial
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
Study design
Double-blind randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Study setting(s)
Hospital
Study type
Treatment
Patient information sheet
Information leaflet for parents: http://www.npeu.ox.ac.uk/boost/downloads/boost_pil.pdf
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
Reason abandoned (if study stopped)
Eligibility
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 type(s)
Patient
Age group
Neonate
Sex
Both
Target number of participants
1200 (973 recruited by end of recruitment)
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
Organisation
University of Oxford (UK)
Sponsor details
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
+44 (0)1865 289728
Kathryn.Dally@admin.ox.ac.uk
Sponsor type
University/education
Website
ROR
Funders
Funder type
Government
Funder name
Medical Research Council (UK)
Alternative name(s)
UK Medical Research Council, MRC
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Individual participant data (IPD) sharing plan
IPD sharing plan summary
Not provided at time of registration
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 |