Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12605000055606
Ethics application status
Approved
Date submitted
14/07/2005
Date registered
1/08/2005
Date last updated
8/06/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
BOOST II: Benefits Of Oxygen Saturation Targeting Study
Scientific title
Which oxygen saturation level should we use for very premature infants? A randomised controlled trial to investigate the effect of two slightly different oxygen levels on the health of very premature infants
Secondary ID [1] 259746 0
Oxygen trial
Secondary ID [2] 259750 0
Oxygen trial
Universal Trial Number (UTN)
Trial acronym
BOOST II
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Preterm infants 126 0
Condition category
Condition code
Reproductive Health and Childbirth 142 142 0 0
Normal pregnancy
Reproductive Health and Childbirth 143 143 0 0
Childbirth and postnatal care

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Lower Oxygen Saturation (85%-89%) versus Higher Oxygen Saturation (91%-95%)
Intervention code [1] 23 0
None
Comparator / control treatment
This is a comparison study and aims to compare the two ranges within the normal clinical practice of 85-95% oxygen saturations. At the moment neither the Lower (85-89%) nor the Higher Oxygen Saturations (91-95%) is seen as the standard, and the purpose of the study is to compare both against each other in order to determine the ideal target within that range.
Control group
Dose comparison

Outcomes
Primary outcome [1] 182 0
Prior to unblinding the data for analysis, a Statistical Analysis Plan was produced and signed off by Prof Tarnow-Mordi, Dr Adrienne Kirby and Prof Val Gebski on 10th February, 2014.

A specific process for determining the primary outcome of death or disability was included, as follows (Section 5.5.)

Infants will be classified as having had the primary endpoint if (a) they have died prior to 2 years corrected gestational age; or (b) assessment at 2 years corrected gestational age shows major disability.

If an infant’s survival status at 2 years is unknown, or they are known to be alive but information on major disability is not available, their primary outcome will be missing.

The classification of infants as having a major disability is determined from:
* Bayley III Developmental Assessment completed by a blinded psychologist; or in some cases Bayley II Developmental Assessment
* Health Status assessment completed by a blinded paediatrician; or in some cases a Short Health Status Questionnaire collected mainly via phone call to parents or a GP visit if this is not available

An infant will be classified as having major disability if they are alive at 2 years corrected gestational age and meet at least one of the following criteria:
* Cerebral palsy with GMFCS level >= 2, as indicated on the health status (Q29) or short health status (Q1) assessments
* Legal blindness, as indicated on the on the health status (Q7) or short health status (Q2) assessments
* Hearing loss requiring hearing aids, as indicated on the health status (Q11) or short health status (Q3) assessments
* Composite cognitive score < 85 or composite language score < 85 on the Bayley III assessment; or cognition Mental Development Index (MDI) < 70 on the Bayley II assessment

If cognitive disability cannot be determined because the relevant Bayley III or Bayley II items are missing, the final criterion above can be replaced by any one of the following from the health status assessment:
* Uses less than 10 words (Q13); or language problems indicated on the short health assessment (Q4)
* Delayed development by more than 12 months (Q32)
* Other severe impairment (Q34)

If the infant does not meet any of the first three criteria, and all information on the Bayley assessment and these substitute criteria is also missing, the infant’s primary endpoint status will be missing.
Timepoint [1] 182 0
At 2 years old corrected for gestation at birth.
Secondary outcome [1] 392 0
ROP of prematurity
Timepoint [1] 392 0
At 2 years old corrected for gestation at birth.
Secondary outcome [2] 393 0
Duration of oxygen therapy
Timepoint [2] 393 0
At 2 years old corrected for gestation at birth.
Secondary outcome [3] 394 0
Duration of respiratory support
Timepoint [3] 394 0
At 2 years old corrected for gestation at birth.
Secondary outcome [4] 395 0
PDA
Timepoint [4] 395 0
At 2 years old corrected for gestation at birth.
Secondary outcome [5] 396 0
NEC
Timepoint [5] 396 0
At 2 years old corrected for gestation at birth.
Secondary outcome [6] 397 0
Chronic lung disease
Timepoint [6] 397 0
Treated with oxygen at 36 weeks gestational age.
Secondary outcome [7] 398 0
Growth
Timepoint [7] 398 0
At 2 years old corrected for gestation at birth.
Secondary outcome [8] 399 0
Re-admissions to hospital
Timepoint [8] 399 0
Up to 2 years old
Secondary outcome [9] 400 0
Cerebral palsy and unable to walk
Timepoint [9] 400 0
At 2 years corrected gestational age.
Secondary outcome [10] 401 0
Blindness (<6/60 vision)
Timepoint [10] 401 0
At 2 years old corrected for gestation at birth.
Secondary outcome [11] 402 0
Deaf using hearing aid
Timepoint [11] 402 0
At 2 years old corrected for gestation at birth.
Secondary outcome [12] 403 0
Mean MDI and PDI scores on Bayley Scales
Timepoint [12] 403 0
At 2 years old corrected for gestation at birth.
Secondary outcome [13] 404 0
Death
Timepoint [13] 404 0
After 4 weeks primarily attributable to pulmonary causes.

Eligibility
Key inclusion criteria
a) born <28 weeks gestation b) less than 24 hours of agec) there is informed consent by parent(s) or legal guardian
Minimum age
0 Days
Maximum age
1 Days
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
a) There is a known congenital anomaly that could affect oxygenation or developmentb) attendance for follow-up for 2 years is judged unlikely.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by phone
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Interactive voice response system (IVRS) and the stratification variables are site, gender, inborn/outborn, gestation and single versus multiple birth.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Prior to unblinding the data for analysis, a Statistical Analysis Plan was produced and signed off by Prof Tarnow-Mordi, Dr Adrienne Kirby and Prof Val Gebski on 10th February, 2014.

A specific process for determining the primary outcome of death or disability was included, as follows (Section 5.5.)

Infants will be classified as having had the primary endpoint if (a) they have died prior to 2 years corrected gestational age; or (b) assessment at 2 years corrected gestational age shows major disability.

If an infant’s survival status at 2 years is unknown, or they are known to be alive but information on major disability is not available, their primary outcome will be missing.

The classification of infants as having a major disability is determined from:
* Bayley III Developmental Assessment completed by a blinded psychologist; or in some cases Bayley II Developmental Assessment
* Health Status assessment completed by a blinded paediatrician; or in some cases a Short Health Status Questionnaire collected mainly via phone call to parents or a GP visit if this is not available

An infant will be classified as having major disability if they are alive at 2 years corrected gestational age and meet at least one of the following criteria:
* Cerebral palsy with GMFCS level >= 2, as indicated on the health status (Q29) or short health status (Q1) assessments
* Legal blindness, as indicated on the on the health status (Q7) or short health status (Q2) assessments
* Hearing loss requiring hearing aids, as indicated on the health status (Q11) or short health status (Q3) assessments
* Composite cognitive score < 85 or composite language score < 85 on the Bayley III assessment; or cognition Mental Development Index (MDI) < 70 on the Bayley II assessment

If cognitive disability cannot be determined because the relevant Bayley III or Bayley II items are missing, the final criterion above can be replaced by any one of the following from the health status assessment:
* Uses less than 10 words (Q13); or language problems indicated on the short health assessment (Q4)
* Delayed development by more than 12 months (Q32)
* Other severe impairment (Q34)

If the infant does not meet any of the first three criteria, and all information on the Bayley assessment and these substitute criteria is also missing, the infant’s primary endpoint status will be missing.


.

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Safety concerns
Date of first participant enrolment
Anticipated
1/08/2005
Actual
25/03/2006
Date of last participant enrolment
Anticipated
Actual
22/12/2010
Date of last data collection
Anticipated
Actual
30/09/2013
Sample size
Target
1200
Accrual to date
Final
1135
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,TAS,WA,VIC
Recruitment outside Australia
Country [1] 7839 0
Taiwan, Province Of China
State/province [1] 7839 0

Funding & Sponsors
Funding source category [1] 198 0
Government body
Name [1] 198 0
NHMRC Grant
Country [1] 198 0
Australia
Primary sponsor type
Government body
Name
NHMRC Clinical Trials Centre
Address
Locked Bag 77, Camperdown, NSW 1450
Country
Australia
Secondary sponsor category [1] 147 0
None
Name [1] 147 0
N/A
Address [1] 147 0
Country [1] 147 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 956 0
Westmead Hospital
Ethics committee address [1] 956 0
Ethics committee country [1] 956 0
Australia
Date submitted for ethics approval [1] 956 0
Approval date [1] 956 0
25/11/2005
Ethics approval number [1] 956 0
Ethics committee name [2] 957 0
Flinders Medical Centre
Ethics committee address [2] 957 0
Ethics committee country [2] 957 0
Australia
Date submitted for ethics approval [2] 957 0
Approval date [2] 957 0
Ethics approval number [2] 957 0
Ethics committee name [3] 958 0
Royal Women's Hospital
Ethics committee address [3] 958 0
Ethics committee country [3] 958 0
Australia
Date submitted for ethics approval [3] 958 0
Approval date [3] 958 0
Ethics approval number [3] 958 0
Ethics committee name [4] 959 0
King Edward Memorial Hospital for Women
Ethics committee address [4] 959 0
Ethics committee country [4] 959 0
Australia
Date submitted for ethics approval [4] 959 0
Approval date [4] 959 0
Ethics approval number [4] 959 0

Summary
Brief summary
Oxygen is the commonest neonatal therapy. Unfortunately, both too much and too little oxygen may be harmful for very premature infants. We now measure the oxygen in a baby's blood by oxygen saturation but the optimum range in the first few weeks is unknown and no randomised controlled trial (RCT) has addressed this question. This proposal is for Australian arm of a major international study involving 5000 babies, born at less than 28 weeks, to address this question. Babies will be randomised to a higher or lower target range of oxygen saturation from birth (85-89% or 91-95%). For all oximeters staff will target a masked range of 88-92%. We will assess which of the two target ranges is associated with the best overall outcome, which is a composite measure of survival, disability on a standard test of neurodevelopment (Bayley scales), and visual function at 2 years of age.
Trial website
http://www.ctc.usyd.edu.au/BoostII/main_body/Home.htm
Trial related presentations / publications
1. Outcomes of Two Trials of Oxygen-Saturation Targets in Preterm Infants.
N Engl J Med. 2016 Feb 10.
2. Oxygen saturation and outcomes in preterm infants.
N Engl J Med. 2013 May 30;368(22):2094-104. doi: 10.1056/NEJMoa1302298. Epub 2013 May 5
Public notes

Contacts
Principal investigator
Name 35875 0
Prof William Tarnow-Mordi
Address 35875 0
NHMRC Clinical Trials Centre
Locked Bag 77
Camperdown
NSW1450
Australia
Country 35875 0
Australia
Phone 35875 0
+61 2 9562 5000
Fax 35875 0
Email 35875 0
[email protected]
Contact person for public queries
Name 9212 0
Dr Alpana Ghadge
Address 9212 0
NHMRC Clinical Trials Centre
Locked Bag 77
Building F 88 Mallett Street
Camperdown Sydney NSW 2050
Country 9212 0
Australia
Phone 9212 0
+61 2 95625000
Fax 9212 0
+61 2 95651863
Email 9212 0
[email protected]
Contact person for scientific queries
Name 140 0
Prof Prof William Tarnow-Mordi
Address 140 0
Professor of Neonatal Medicine
NHMRC Clinical Trials Centre
University of Sydney
Camperdown
NSW 2050
Country 140 0
Australia
Phone 140 0
+61 2 98458900
Fax 140 0
+61 2 98457490
Email 140 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseOptimal oxygenation of extremely low birth weight infants: A meta-analysis and systematic review of the oxygen saturation target studies.2014https://dx.doi.org/10.1159/000356561
EmbaseUsual care and informed consent in clinical trials of oxygen management in extremely premature infants.2016https://dx.doi.org/10.1371/journal.pone.0155005
Dimensions AIIncreased 36-Week Survival with High Oxygen Saturation Target in Extremely Preterm Infants2011https://doi.org/10.1056/nejmc1101319
Dimensions AINeOProM: Neonatal Oxygenation Prospective Meta-analysis Collaboration study protocol2011https://doi.org/10.1186/1471-2431-11-6
N.B. These documents automatically identified may not have been verified by the study sponsor.