Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000529842
Ethics application status
Approved
Date submitted
26/03/2021
Date registered
6/05/2021
Date last updated
17/03/2024
Date data sharing statement initially provided
6/05/2021
Date results information initially provided
19/09/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Giving donor milk instead of formula in moderate-late preterm infants: the pilot GIFT trial
Scientific title
Effect of supplementary pasteurised donor human milk compared with standard formula on time to full enteral feeds, feed tolerance, growth, breastfeeding and length of hospital stay in moderate and late preterm babies – a pilot randomised controlled trial
Secondary ID [1] 303808 0
None
Universal Trial Number (UTN)
Trial acronym
GIFT
Linked study record
Not applicable.

Health condition
Health condition(s) or problem(s) studied:
Preterm birth 321310 0
Poor neonatal nutrition 321780 0
Condition category
Condition code
Diet and Nutrition 319098 319098 0 0
Other diet and nutrition disorders
Reproductive Health and Childbirth 319106 319106 0 0
Complications of newborn
Reproductive Health and Childbirth 319107 319107 0 0
Breast feeding

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Pasteurised donor human milk, supplied by Australian Red Cross Lifeblood.

Infants will be fed with maternal breast milk each day (if available) and then supplemented with pasteurised donor human milk in a volume as determined by the treating health care team, based on the target volume of 150ml/kg/day or as specified in local unit protocols.

Infants will receive pasteurised donor human milk for up to 8 days, but this may be ceased earlier if maternal breast milk supply is sufficient to feed at a rate of 150ml/kg/day OR if the infant is discharged.

Adherence to the intervention will be monitored by review of fluid balance charts held in the infant medical record.
Intervention code [1] 320107 0
Treatment: Other
Comparator / control treatment
Standard term infant formula, providing 20 calories per 30ml (which is consistent across major brands). Formula will be provided by the neonatal unit during the hospitalisation.

Infants will be fed with maternal breast milk each day (if available), and then supplemented with standard infant formula in a volume as determined by the treating health care team, based on the target volume of 150ml/kg/day or local unit protocols..

Infants will receive the infant formula for up to 8 days, but this may be ceased earlier if maternal breast milk supply is sufficient to feed at a rate of 150ml/kg/day OR if the infant is discharged.
Control group
Active

Outcomes
Primary outcome [1] 326986 0
Time to full enteral feeds (days), assessed by review of infant medical records.
Timepoint [1] 326986 0
Time from randomisation until 150ml/kg/day enteral feeds is reached, assessed until hospital discharge.
Secondary outcome [1] 393346 0
Number of episodes of feed intolerance during the intervention phase, assessed by review of infant medical records.
Timepoint [1] 393346 0
The number of times there was a documented decision to delay or stop enteral feeds, from the time of randomisation until the end of the intervention period, assessed by review of infant medical records.
Secondary outcome [2] 393347 0
Total number of episodes of feed intolerance, assessed by review of infant medical records.
Timepoint [2] 393347 0
The number of times there was a documented decision to delay or stop enteral feeds, from the time of randomisation until discharge from the initial hospitalisation
Secondary outcome [3] 393348 0
Time to establish full suck feeds (days), assessed by review of infant medical records and parental report (if after hospital discharge).
Timepoint [3] 393348 0
Time from randomisation until full suck feeds is reached, followed up until the infant is 6 months' corrected age.
Secondary outcome [4] 393349 0
Duration of use of IV glucose, assessed by review of infant medical records.
Timepoint [4] 393349 0
Time from randomisation until IV glucose is ceased until discharge from hospital.
Secondary outcome [5] 393350 0
Duration of use of parenteral nutrition, assessed by review of infant medical records.
Timepoint [5] 393350 0
Time from randomisation until parenteral nutrition is ceased until discharge from hospital.
Secondary outcome [6] 393352 0
Time to regain birth weight (days), assessed using neonatal balance scales.
Timepoint [6] 393352 0
Time from randomisation until birth weight is gained, followed up until the infant is 6 months' corrected age.
Secondary outcome [7] 393353 0
Weight z-score for gestational age, assessed using neonatal balance scales and calculated using Fenton growth charts.
Timepoint [7] 393353 0
At discharge.
Secondary outcome [8] 393354 0
Change in weight z-score for gestational age, assessed using neonatal balance scales and calculated using Fenton growth charts.
Timepoint [8] 393354 0
Assessed using the weight measurement closest to randomisation and the last measurement prior to discharge from the initial hospitalisation
Secondary outcome [9] 393355 0
Weight, assessed using balance scales.
Timepoint [9] 393355 0
At discharge, 2 and 4 months' corrected age.
Secondary outcome [10] 393356 0
Length, assessed as recumbent length using a length board.
Timepoint [10] 393356 0
At discharge, 2 and 4 months' corrected age.
Secondary outcome [11] 393357 0
Head circumference, assessed using a tape measure.
Timepoint [11] 393357 0
At discharge, 2 and 4 months' corrected age.
Secondary outcome [12] 393358 0
% fat free mass, assessed using air displacement plethysmography.
Timepoint [12] 393358 0
At discharge, 2 and 4 months' corrected age.
Secondary outcome [13] 393359 0
% fed breast milk, assessed by parental report.
Timepoint [13] 393359 0
At discharge, 2, 4 and 6 month's corrected age.
Secondary outcome [14] 393394 0
Length of initial hospitalisation (days), assessed by review of infant medical records.
Timepoint [14] 393394 0
Time from randomisation until discharge from initial hospitalisation.
Secondary outcome [15] 393395 0
Number of episodes of hospital readmission, assessed by review of infant medical records, and parental report.
Timepoint [15] 393395 0
From the date of initial hospital discharge to 6 months' corrected age.
Secondary outcome [16] 393396 0
Length of hospital readmissions, assessed by parental report.
Timepoint [16] 393396 0
From the date of initial hospital discharge to 6 months' corrected age.
Secondary outcome [17] 393397 0
Confirmed sepsis, assessed by review of infant medical records.
Timepoint [17] 393397 0
From randomisation until initial hospital discharge.
Secondary outcome [18] 393398 0
Confirmed necrotising enterocolitis, assessed by review of infant medical records,
Timepoint [18] 393398 0
From randomisation until initial hospital discharge.
Secondary outcome [19] 393399 0
Method of feeding (breast, bottle, tube, mixed), assessed by parental report.
Timepoint [19] 393399 0
At discharge, 2, 4 and 6 months' corrected age.

Eligibility
Key inclusion criteria
Eligible infants must meet all of the following criteria:
1. 32+0 and 36+6 completed weeks’ gestation at birth;
2. Birth weight 1500g or more;
3, Admitted to the neonatal unit;
4. Clinically stable;
5. Ready to commence enteral feeds or commenced enteral feeds with human milk but insufficient maternal breast milk is available;
6. Aged less than or equal to 4 days old;
7. Has a parent or guardian capable of giving informed consent.
Minimum age
0 Hours
Maximum age
4 Days
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
An infant who meets any of the following criteria will be excluded from participation:
1. Metabolic disorder that precludes breastfeeding;
2. Major congenital malformation either likely to interfere with the ability to ingest milk or requiring surgery in the first 6 months of life;
3. Given infant formula prior to randomisation.

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 via computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
This is a pilot study intended to generate evidence to inform the development of a large multicenter trial.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
A sample size of 100 infants per group will provide over 80% power to detect a reduction in the mean time to full enteral feeds (days) between the treatment groups of 0.5 standard deviations, with a two-sided alpha of 0.05 and 5% loss to follow-up. This calculation assumes 24% of infants will be twins and allows for a worst-case scenario of perfect correlation between outcomes of twins. This sample size exceeds the minimum recommendations for pilot studies to provide accurate parameter estimates for planning a larger definitive trial.

The primary outcome of time to full enteral feeds will be analysed using linear regression; no censoring is expected due to the length of the follow-up period. Generalised estimating equations (GEEs) will be used to account for clustering due to multiple births. Analyses will be performed on an intention-to-treat basis and a two-sided P-value <0.05 will be considered statistically significant. Secondary outcomes will be analysed using linear regression models for continuous outcomes and log binomial regression models for binary outcomes, with adjustment for clustering using GEEs. A detailed statistical analysis plan will be developed prior to the commencement of the trial.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/06/2021
Actual
6/07/2021
Date of last participant enrolment
Anticipated
Actual
5/04/2023
Date of last data collection
Anticipated
30/11/2023
Actual
4/12/2023
Sample size
Target
200
Accrual to date
Final
201
Recruitment in Australia
Recruitment state(s)
QLD,SA

Funding & Sponsors
Funding source category [1] 308206 0
Charities/Societies/Foundations
Name [1] 308206 0
Ramaciotti Health Investment Grant
Country [1] 308206 0
Australia
Primary sponsor type
Other Collaborative groups
Name
South Australia Health and Medical Research Institute
Address
PO Box 11060, Adelaide SA 5001
Country
Australia
Secondary sponsor category [1] 308989 0
None
Name [1] 308989 0
Address [1] 308989 0
Country [1] 308989 0
Other collaborator category [1] 281701 0
Other
Name [1] 281701 0
Australian Red Cross Lifeblood
Address [1] 281701 0
17 O’Riordan Street
Alexandria NSW 2015
Country [1] 281701 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308187 0
Womens and Children's Health Network
Ethics committee address [1] 308187 0
Research Secretariat
Level 2, Samuel Way Building
72 King William Road
North Adelaide, SA 5006
Ethics committee country [1] 308187 0
Australia
Date submitted for ethics approval [1] 308187 0
Approval date [1] 308187 0
16/12/2020
Ethics approval number [1] 308187 0
HREC/20/WCHN/126

Summary
Brief summary
Babies that are born too soon (preterm) are at risk of slow growth and delayed development. This can affect lifelong health. Exclusive breastfeeding and use of breast milk is a key way to improve outcomes for babies born preterm but these babies often have problems breastfeeding and their mothers can find it hard to produce enough milk, especially in the first few weeks after birth. As a result, many are given infant formula, which can be difficult to digest and is sometimes harmful to preterm babies as they are born before their gut is fully developed. Feeding babies with pasteurised donor human milk has been shown to improve health outcomes for babies born very early but we do not know if it benefits babies born just a few weeks early (moderate to late preterm). The primary aim of this randomised controlled trial is to determine whether using donor human milk, instead of infant formula, in the critical early weeks after birth improves nutrition and growth of moderate to late preterm infants, and supports their mothers to continue breastfeeding in the first 6 months after birth. The trial will be conducted in partnership with Australian Red Cross Lifeblood.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 109854 0
A/Prof Alice Rumbold
Address 109854 0
SAHMRI Women and Kids
72 King William Road
North Adelaide, SA 5006
Country 109854 0
Australia
Phone 109854 0
+61881284194
Fax 109854 0
Email 109854 0
[email protected]
Contact person for public queries
Name 109855 0
A/Prof Alice Rumbold
Address 109855 0
SAHMRI Women and Kids
72 King William Road
North Adelaide, SA 5006
Country 109855 0
Australia
Phone 109855 0
+61881284194
Fax 109855 0
Email 109855 0
[email protected]
Contact person for scientific queries
Name 109856 0
A/Prof Alice Rumbold
Address 109856 0
SAHMRI Women and Kids
72 King William Road
North Adelaide, SA 5006
Country 109856 0
Australia
Phone 109856 0
+61881284194
Fax 109856 0
Email 109856 0
[email protected]

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?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
11184Study protocol  [email protected]



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Plain language summaryNo Findings are currently being written up for public... [More Details]

Documents added automatically
No additional documents have been identified.