Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000778886
Ethics application status
Approved
Date submitted
23/03/2021
Date registered
22/06/2021
Date last updated
8/03/2022
Date data sharing statement initially provided
22/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of targeting brain oxygenation on neuro-developmental outcomes in extremely pre-term infants: A pilot blinded randomised controlled trial
Scientific title
Does Near Infra-Red spectroscopy Targeted Use Reduce adverse outcomes in Extremely preterm infants? (NIRTURE trial)
Secondary ID [1] 303764 0
None
Universal Trial Number (UTN)
U1111-1265-9746
Trial acronym
NIRTURE
Linked study record
None

Health condition
Health condition(s) or problem(s) studied:
Premature birth 321251 0
brain injury 321252 0
Condition category
Condition code
Reproductive Health and Childbirth 319033 319033 0 0
Complications of newborn
Neurological 319034 319034 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
NIRTURE trial will be a single-blinded randomised controlled trial with two parallel groups that are stratified for site and gestational age (less than 26 weeks and greater than or equal to 26+0 – 28+6 weeks gestation). Enrolment will occur after birth of the baby. After enrolment, infants will be randomised to either control group or intervention group. For all enrolled babies, monitoring of cerebral oxygenation will be commenced by placement of a non-adhesive probe on the fronto-parietal region of the forehead within 6 hours of birth and monitoring will be continued for 5 days.

For the intervention group, the cerebral oxygenation (crSO2) reading is visible and the baby will be treated according to a dedicated clinical guideline when the cerebral oxygenation is outside the range of 65% to 90%. The probe will be moved every 4 hours. The intervention will be delivered by the bedside medical and nursing team using a treatment algorithm. Research team will review the adherence to the protocol with bedside forms when the crSo2 is is less than 65% or more than 90%. The dedicated clinical guideline was designed based on the evidence that affected regional oxygen saturation. Cerebral oxygen monitoring and intervention will cease after 5 days of age.
Intervention code [1] 320076 0
Prevention
Intervention code [2] 320454 0
Treatment: Devices
Intervention code [3] 320455 0
Treatment: Other
Comparator / control treatment
For the Control group, cerebral oxygenation reading is NOT visible and the baby will be treated according to standard clinical practice (as per local site practices, that is if the baby has hypotension based on blood pressure monitoring, then a bolus of normal saline followed by inotropes if required is commenced). We will perform blinded cerebral oxygenation monitoring (we will cover the monitor) and the information will not be available to clinicians to act upon.
Control group
Active

Outcomes
Primary outcome [1] 326938 0
cerebral oxygen saturation assessed using a near-infrared spectroscopy probe placed on the fronto-parietal region of the forehead
Timepoint [1] 326938 0
Monitored continuously from within 6 hours of birth to 5 days post-birth
Secondary outcome [1] 393187 0
• Newborn mortality rates assessed by accessing patient medical records
Timepoint [1] 393187 0
prior to home discharge.
Secondary outcome [2] 393189 0
• Motor performance assessment (General movements assessment)
Timepoint [2] 393189 0
during NICU stay and at 4 months corrected age follow up.
Secondary outcome [3] 393190 0
• Neuro-developmental outcomes using Bayley Scales of Infant Development (BSID) IVth Edition tool (cognition scaled score, cognition standard score, receptive language scaled score, expressive language scaled score, language standard score, fine motor scaled score, gross motor scaled score, motor standard score)
Timepoint [3] 393190 0
2 years post-intervention completion.
Secondary outcome [4] 393191 0
• Measurement of heart rate (assessed by oximeter)
Timepoint [4] 393191 0
Monitored continuously from within 6 hours of birth to 5 days post-birth
Secondary outcome [5] 394943 0
• Brain injury based on cerebral imaging (head ultrasound and / MRI brain),
Timepoint [5] 394943 0
Prior to home discharge
Secondary outcome [6] 394944 0

chronic lung disease
Timepoint [6] 394944 0
Prior to home discharge by accessing patient medical records
Secondary outcome [7] 394945 0
• Neuro-developmental outcomes using Wechsler Preschool and Primary Scale of Intelligence tool (verbal comprehension, visual spatial, fluid reasoning, working memory, processing speed, Full scale IQ)
Timepoint [7] 394945 0
5 years post intervention
Secondary outcome [8] 396532 0
Monitoring of peripheral saturation (assessed by oximeter)
Timepoint [8] 396532 0
Monitored continuously from within 6 hours of birth to 5 days post-birth
Secondary outcome [9] 396533 0
Necrotising enterocolitis
Timepoint [9] 396533 0
Prior to home discharge by accessing patient medical records
Secondary outcome [10] 396534 0
Retinopathy of prematurity
Timepoint [10] 396534 0
Prior to home discharge by accessing patient medical records

Eligibility
Key inclusion criteria
• Preterm infants (singleton or twin births) less than 29 weeks gestation who are either inborn (born at the local study site hospital) or outborn (born outside the local study site hospital) and less than 6 hours of age when admitted to the study site NICU.
Minimum age
0 Hours
Maximum age
6 Hours
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

• Infants with an antenatal or postnatal diagnosis of major congenital anomaly requiring major surgery or a genetic disorder associated with neurological impairment.
• Multiple births beyond twins are excluded for practical reasons (sites may not have additional NIRS monitors and the rates of multiple births beyond twins in Australia and New Zealand is very low < 2%).

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
central randomisation by phone/fax/computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
variable block randomisation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?

The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
A 50% reduction in mean burden of hypoxia and hyperoxia in active treatment relative to control would be considered worthwhile. This corresponds to a reduction of 0.3 in the mean of log-transformed burden. In the Safe BoosC II study (BoosC results) a 58% reduction was achieved. Assuming a standard deviation of 0.5 in log-transformed burden (Ref – BoosC protocol), this would require 45 babies per group to achieve 80% power at 5% two-sided alpha. To account for the clustering effect of twins being allocated to the same treatment, we assume that 30% of babies are twins (giving an average cluster size of 1.3, and a within-twin correlation of 0.1 in the outcome. This gives a design effect of 1.03 by which the sample size is adjusted, leading to a sample size of 47 per group, 94 babies in total. We aim to recruit 100 babies to account for some loss to follow-up or missing data.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
26/07/2021
Actual
14/10/2021
Date of last participant enrolment
Anticipated
30/12/2022
Actual
Date of last data collection
Anticipated
30/12/2027
Actual
Sample size
Target
100
Accrual to date
30
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 18989 0
Westmead Hospital - Westmead
Recruitment hospital [2] 18990 0
Nepean Hospital - Kingswood
Recruitment hospital [3] 18991 0
Royal Hospital for Women - Randwick
Recruitment postcode(s) [1] 33506 0
2031 - Randwick
Recruitment postcode(s) [2] 33504 0
2145 - Westmead
Recruitment postcode(s) [3] 33505 0
2747 - Kingswood
Recruitment outside Australia
Country [1] 23558 0
New Zealand
State/province [1] 23558 0
Wellington
Country [2] 23559 0
United States of America
State/province [2] 23559 0
Connecticut

Funding & Sponsors
Funding source category [1] 308170 0
Charities/Societies/Foundations
Name [1] 308170 0
Research Foundation, Cerebral Palsy Alliance
Country [1] 308170 0
Australia
Primary sponsor type
Government body
Name
Western Sydney Local Health District
Address
Research Office
Western Sydney Local Health District
Westmead Hospital
Hawkesbury and Darcy Rds.
Westmead NSW 2145
Country
Australia
Secondary sponsor category [1] 308942 0
None
Name [1] 308942 0
Address [1] 308942 0
Country [1] 308942 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308155 0
The Sydney Children's Ethics Committee
Ethics committee address [1] 308155 0
Corner Hawkesbury Road and Hainsworth Street
Locked Bag 4001
Westmead NSW 2145
Sydney Australia
DX 8213 Parramatta
Ethics committee country [1] 308155 0
Australia
Date submitted for ethics approval [1] 308155 0
27/11/2020
Approval date [1] 308155 0
08/12/2020
Ethics approval number [1] 308155 0
2020/ETH02903

Summary
Brief summary
Preterm babies can develop brain injury which leads to long-term developmental problems. Most brain injuries occur within the first 5 days of life and protection of the brain during this critical period is essential. Fluctuating brain oxygen levels is one reason for brain injury to develop, which can also cause bleeding in the brain. Keeping brain oxygen levels in a specific range may be protective. The purpose of the study is to investigate in preterm babies, whether it is possible to keep brain oxygen levels in a specific range for the first 5 days by NIRS monitoring and following a dedicated clinical treatment guideline. We hypothesise that a combination of brain oxygen monitoring and offering treatment when brain oxygen levels are outside the range may reduce fluctuations in brain oxygen levels and reduce brain injury. Babies in this study will have either (a) the usual treatment (given to all babies), or (b) they will be in the group where the focus is on keeping brain oxygen levels in a specific range for the first 5 days of life using NIRS monitoring.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 109726 0
Dr Pranav Jani
Address 109726 0
Neonatal Intensive Care Unit
Level 3
Westmead Hospital
Hawkesbury and Darcy Rds
Westmead NSW 2145
Country 109726 0
Australia
Phone 109726 0
+61 2 8890 8911
Fax 109726 0
+61 2 8890 7490
Email 109726 0
pranav.jani@health.nsw.gov.au
Contact person for public queries
Name 109727 0
Himanshu Popat
Address 109727 0
Grace Centre for Newborn Care
The Children's Hospital at Westmead Hawkesbury and Darcy Rds
Westmead, NSW 2145.
Country 109727 0
Australia
Phone 109727 0
+61 2 9845 2715
Fax 109727 0
+61 2 9845 2251
Email 109727 0
Himanshu.Popat@health.nsw.gov.au
Contact person for scientific queries
Name 109728 0
Traci-Anne Goyen
Address 109728 0
Neonatal Intensive Care Unit
Level 3
Westmead Hospital
Hawkesbury and Darcy Rds
Westmead NSW 2145
Country 109728 0
Australia
Phone 109728 0
+61 2 8890 7375
Fax 109728 0
+61 2 8890 7490
Email 109728 0
traci-anne.goyen@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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
No additional documents have been identified.