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Trial registered on ANZCTR


Registration number
ACTRN12624000289516
Ethics application status
Approved
Date submitted
20/02/2024
Date registered
20/03/2024
Date last updated
21/07/2024
Date data sharing statement initially provided
20/03/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Giving Donor Milk Instead of Formula in Moderate-Late Preterm Infants: the GIFT trial
Scientific title
Effect of supplementary pasteurised donor human milk compared with infant formula on length of neonatal hospital stay, morbidity, breastfeeding, growth, development and health care costs in moderate and late preterm babies – a randomised controlled trial
Secondary ID [1] 310950 0
Nil known
Universal Trial Number (UTN)
Trial acronym
GIFT
Linked study record
ACTRN12621000529842 is a pilot study that informed this large multi-centre trial.

Health condition
Health condition(s) or problem(s) studied:
Feeding intolerance 332028 0
Condition category
Condition code
Oral and Gastrointestinal 328757 328757 0 0
Normal oral and gastrointestinal development and function
Reproductive Health and Childbirth 329838 329838 0 0
Breast feeding
Reproductive Health and Childbirth 329839 329839 0 0
Complications of newborn

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Pasteurised donor human milk provided by Australian Red Cross Lifeblood. All milk will undergo microbiological screening before and after Holder pasteurisation (30 minutes at 62.5°C) according to Lifeblood policies. Mother’s own breast milk will always be given first and if supplementary feeds are required, then study nutrition will be used. Feeds will start at 10-15 ml/kg/day, and increasing 10-15 ml/kg/day or as per clinician discretion. Study nutrition will be provided from the day of randomisation for 15 days or earlier if there is sufficient mother’s own breast milk to support the target fluid intake, or the infant is discharged from hospital, to postnatal ward or transferred to another hospital. A research nurse will monitor fluid balance charts to monitor adherence to the study protocol during the intervention phase.
Intervention code [1] 327377 0
Treatment: Other
Comparator / control treatment
Infant formula, with the type and brand to be determined by each site. Sites will be using either standard term formula or standard preterm formula routinely used at the site. Mother’s own breast milk will always be given first and if supplementary feeds are required, then study nutrition will be used. Feeds will start at 10-15 ml/kg/day, and increasing 10-15 ml/kg/day or as per clinician discretion. Study nutrition will be provided from the day of randomisation for 15 days or earlier if there is sufficient mother’s own breast milk to support the target fluid intake, or the infant is discharged from hospital, to postnatal ward or transferred to another hospital. A research nurse will monitor fluid balance charts to monitor adherence to the study protocol during the intervention phase.
Control group
Active

Outcomes
Primary outcome [1] 336562 0
Length of neonatal hospital stay (days)
Timepoint [1] 336562 0
At discharge from hospital
Secondary outcome [1] 431226 0
Frequency of feed intolerance
Timepoint [1] 431226 0
At discharge from hospital
Secondary outcome [2] 431227 0
Time to establish full oral feeds during hospital stay (days)
Timepoint [2] 431227 0
At discharge from hospital
Secondary outcome [3] 431228 0
Episodes of hypoglycaemia during hospital stay
Timepoint [3] 431228 0
At discharge from hospital
Secondary outcome [4] 431229 0
Frequency of jaundice requiring phototherapy during hospital stay
Timepoint [4] 431229 0
At discharge from hospital
Secondary outcome [5] 431230 0
Use and duration of supplements
Timepoint [5] 431230 0
Data during hospital stay will be collected at discharge from hospital
Data reported by parents will be collected at 2, 4, 6, 12 and 18 month corrected age
Secondary outcome [6] 431231 0
Use and duration of parenteral nutrition during hospital stay
Timepoint [6] 431231 0
At discharge from hospital
Secondary outcome [7] 431232 0
Duration of IV Glucose/Dextrose during hospital stay
Timepoint [7] 431232 0
At discharge from hospital
Secondary outcome [8] 431679 0
Type of feeding methods including Nasogastric Tube during hospital stay. This will be assessed separately.
Timepoint [8] 431679 0
At discharge from hospital
Secondary outcome [9] 431683 0
Proven late onset sepsis during hospital stay
Timepoint [9] 431683 0
At discharge from hospital
Secondary outcome [10] 431685 0
Proven necrotising enterocolitis during hospital stay
Timepoint [10] 431685 0
At discharge from hospital
Secondary outcome [11] 431690 0
Diagnoses and conditions
Timepoint [11] 431690 0
At discharge from hospital and at 2, 4, 6, 12 and 18 months corrected age
Secondary outcome [12] 431692 0
Frequency of breastfeeding
Timepoint [12] 431692 0
At discharge from hospital and at 2, 4, 6, 12 and 18 months corrected age
Secondary outcome [13] 431693 0
Self-reported breastfeeding challenges, use of medications and foods or ingredients to boost breast milk supply and type of feeding methods used. This will be assessed separately.
Timepoint [13] 431693 0
At discharge from hospital and at 2, 4 and 6 months corrected age
Secondary outcome [14] 431696 0
Mean fat free mass percentage of total body mass
Timepoint [14] 431696 0
At discharge from hospital and at 4 months corrected age in select sites
Secondary outcome [15] 431698 0
Mean total body fat percentage
Timepoint [15] 431698 0
At discharge from hospital and at 4 months corrected age in select sites
Secondary outcome [16] 431699 0
Time to regain birth weight (days)
Timepoint [16] 431699 0
At discharge from hospital
Secondary outcome [17] 431701 0
Infant weight z-score for gestational age at discharge
Timepoint [17] 431701 0
At discharge from hospital
Secondary outcome [18] 431702 0
Infant length z-score for gestational age at discharge
Timepoint [18] 431702 0
At discharge from hospital
Secondary outcome [19] 431703 0
Infant head circumference z-score for gestational age at discharge
Timepoint [19] 431703 0
At discharge from hospital
Secondary outcome [20] 431704 0
Weight z-score change from birth to discharge
Timepoint [20] 431704 0
At discharge from hospital
Secondary outcome [21] 431705 0
Length z-score change from birth to discharge
Timepoint [21] 431705 0
At discharge from hospital
Secondary outcome [22] 431706 0
Head circumference z-score change from birth to discharge
Timepoint [22] 431706 0
At discharge from hospital
Secondary outcome [23] 431707 0
Weight measurement (g)
Timepoint [23] 431707 0
At 2, 4, 6, 12 and 18 months corrected age
Secondary outcome [24] 431708 0
Frequency of breast milk feeds (including expressed breast milk given via bottle)
Timepoint [24] 431708 0
At discharge from hospital and at 2, 4, 6, 12 and 18 months corrected age
Secondary outcome [25] 431709 0
Parent-reported general development
Timepoint [25] 431709 0
At 12 and 18 months corrected age
Secondary outcome [26] 431710 0
Parent-reported feeding behaviours
Timepoint [26] 431710 0
At 18 months corrected age
Secondary outcome [27] 431711 0
Parental wellbeing
Timepoint [27] 431711 0
At discharge and 12 months corrected age
Secondary outcome [28] 431712 0
Ratings of experience of the trial
Timepoint [28] 431712 0
At 6 months corrected age
Secondary outcome [29] 431713 0
Care and degree of lactation support during the hospitalisation. This will be assessed as a composite outcome.
Timepoint [29] 431713 0
At enrolment and at discharge from hospital
Secondary outcome [30] 431714 0
Neonatal length of stay (days) sub-grouped by acuity of care (neonatal intensive care, special care and transitional care) reported separately
Timepoint [30] 431714 0
At discharge from hospital
Secondary outcome [31] 431715 0
Maternal length of stay in hospital (days)
Timepoint [31] 431715 0
At discharge from hospital
Secondary outcome [32] 431716 0
Costs associated with use of donor milk
Timepoint [32] 431716 0
During the study period
Secondary outcome [33] 431717 0
Costs associated with the neonatal hospitalisation
Timepoint [33] 431717 0
From birth to discharge from hospital
Secondary outcome [34] 431718 0
Costs associated with donor milk provision
Timepoint [34] 431718 0
During the study period
Secondary outcome [35] 431719 0
Admission costs by gestational age category
Timepoint [35] 431719 0
From birth to discharge from hospital
Secondary outcome [36] 431720 0
Health services utilisation from birth to 18 months corrected age
Timepoint [36] 431720 0
Birth to 18 months corrected age
Secondary outcome [37] 431721 0
Safety Adverse Events
Timepoint [37] 431721 0
During the intervention period
Secondary outcome [38] 431722 0
Safety Serious Adverse Events
Timepoint [38] 431722 0
During the study period
Secondary outcome [39] 431731 0
Volume and type of milk feeds during hospital stay. This will be assessed separately.
Timepoint [39] 431731 0
At discharge from hospital
Secondary outcome [40] 432492 0
Parental satisfaction
Timepoint [40] 432492 0
At discharge from hospital

Eligibility
Key inclusion criteria
- 32+0 and 36+6 completed weeks’ gestation at birth;*
- Birth weight >= 1500g;
- Admitted to the neonatal unit;**
- Clinically stable as determined by the treating physician;
- Ready to commence enteral feeds or commenced enteral feeds with human milk but insufficient maternal breast milk is available as decided by the treating health care team;
- Aged <= 96 hours;
- Has a parent or guardian who is at least 16 years of age and is capable of giving informed consent.

*Only infants with a gestation of >=34 weeks at birth will be enrolled at the Royal Brisbane and Women’s Hospital, this is consistent with the process undertaken in our pilot study.

**If it is anticipated that an infant will be transferred to the postnatal ward or another hospital quickly (e.g. within 8 hours) then they will not be eligible for the study, as for practical reasons the study nutrition will not be able to be administered on the postnatal ward or to non-participating hospitals.
Minimum age
0 Hours
Maximum age
96 Hours
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Documented, suspected or confirmed metabolic disorder that precludes breastfeeding;
- Major congenital malformation either likely to interfere with the ability to ingest milk or requiring surgery in the first 6 months of life ((including abnormalities of the central nervous system, cardiovascular system, urinary system, gastrointestinal system, chromosomal, metabolic, musculoskeletal, respiratory, diaphragmatic hernia, haematological, tumours or any other unspecified major abnormality);
- Has been 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)
Infants will be randomly allocated to either the intervention or control group with a 1:1 allocation using a secure web-based randomisation service on the REDCap platform.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computer-generated randomisation schedule using balanced variable blocks will be prepared by an independent statistician. Stratification will occur for site and gestational age (<34 weeks, >=34 weeks). A computer-generated randomisation schedule using balanced variable block design will be prepared and held by an independent statistician, not otherwise involved in the trial. Twins and triplets will be co-randomised to the same treatment arm.
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
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The primary outcome of length of neonatal hospital stay will be compared between the randomised groups using a linear regression model with robust variance estimation due to the likely skewed distribution of the data. Adjustment will be made for the stratification variables (gestational age, site) and pre-specified prognostic baseline variables (e.g., multiplicity). Sensitivity analyses will be performed using a linear regression model with bootstrap CIs and a generalised linear model with the distribution and link function informed by the data.
Secondary outcomes will be analysed using linear regression models for continuous outcomes and log binomial regression models for binary outcomes. For infant outcomes, generalised estimating equations will be used to account for clustering due to multiple births. All analyses will follow a pre-specified analysis plan.
Analysis of healthcare costs: The economic value of donor milk for this population will be assessed in terms of cost-savings due to reductions in the risk and severity of neonatal morbidities, and the length of the neonatal hospitalisation. Taking a healthcare system perspective, within-trial incremental costs associated with the two trial arms (including costs associated with the intervention and hospital services) will be estimated. Generalised linear models (GLM) will be fitted to estimate and compare costs between the donor milk and control groups. Goodness of fit will be tested using the modified Park test (for the GLM family) and the Pearson correlation test, the Pregibon link test, and the modified Hosmer and Lemeshow test (for the GLM link). A bootstrapping approach will be applied to represent sampling uncertainty. A costing model will be developed with data from the trial and published literature. This will be used to extrapolate the findings to the national level and assess parameter uncertainty, to predict the costs of alternative scenarios (e.g., current practice vs. expanding access to donor milk to this population).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA

Funding & Sponsors
Funding source category [1] 315210 0
Government body
Name [1] 315210 0
National Health and Medical Research Institute (NHMRC)
Country [1] 315210 0
Australia
Primary sponsor type
Other Collaborative groups
Name
South Australian Health and Medical Research Institute
Address
Country
Australia
Secondary sponsor category [1] 317817 0
None
Name [1] 317817 0
Address [1] 317817 0
Country [1] 317817 0
Other collaborator category [1] 282954 0
Charities/Societies/Foundations
Name [1] 282954 0
Australian Red Cross Lifeblood
Address [1] 282954 0
Country [1] 282954 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314135 0
Women's and Children's Health Network Human Research Ethics Committee
Ethics committee address [1] 314135 0
Ethics committee country [1] 314135 0
Australia
Date submitted for ethics approval [1] 314135 0
11/10/2023
Approval date [1] 314135 0
13/12/2023
Ethics approval number [1] 314135 0
2023/HRE00241

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 130538 0
Prof Alice Rumbold
Address 130538 0
South Australian Health and Medical Research Institute (SAHMRI), 72 King William Road, North Adelaide SA 5006 Australia
Country 130538 0
Australia
Phone 130538 0
+61881284194
Fax 130538 0
Email 130538 0
Contact person for public queries
Name 130539 0
Alice Rumbold
Address 130539 0
South Australian Health and Medical Research Institute (SAHMRI), 72 King William Road, North Adelaide SA 5006 Australia
Country 130539 0
Australia
Phone 130539 0
+61881284194
Fax 130539 0
Email 130539 0
Contact person for scientific queries
Name 130540 0
Alice Rumbold
Address 130540 0
South Australian Health and Medical Research Institute (SAHMRI), 72 King William Road, North Adelaide SA 5006 Australia
Country 130540 0
Australia
Phone 130540 0
+61881284194
Fax 130540 0
Email 130540 0

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.