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Trial registered on ANZCTR


Registration number
ACTRN12611000247976
Ethics application status
Approved
Date submitted
3/03/2011
Date registered
7/03/2011
Date last updated
4/03/2019
Date data sharing statement initially provided
4/03/2019
Date results information initially provided
4/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Does lactoferrin improve survival free from morbidity in very low birth weight
infants?
Lactoferrin Infant Feeding Trial: a randomised controlled trial
Scientific title
Does lactoferrin improve survival free from morbidity in very low birth weight
infants?
Lactoferrin Infant Feeding Trial: a randomised controlled trial
Secondary ID [1] 259730 0
Nil
Universal Trial Number (UTN)
Trial acronym
LIFT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Premature babies 261310 0
sepsis 261314 0
Condition category
Condition code
Infection 259460 259460 0 0
Other infectious diseases
Reproductive Health and Childbirth 259463 259463 0 0
Complications of newborn

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Bovine Lactoferrin (BLF): Dosage - 200 mg/kg/day added to breast milk or formula, once daily.
Study intervention is administered until 34 weeks corrected gestation or for 2 weeks, whichever is longer, or until discharge home, if earlier.
Intervention code [1] 264156 0
Prevention
Comparator / control treatment
Control: no BLF added to breast milk or formula, once daily.
Study intervention is administered until 34 weeks corrected gestation or for 2 weeks, whichever is longer, or until discharge home, if earlier.
Control group
Placebo

Outcomes
Primary outcome [1] 262267 0
Survival to hospital discharge free from (i) 3 morbidities diagnosed or treated in hospital by 36
weeks corrected gestational age: brain injury or late onset sepsis or necrotising enterocolitis
(NEC); and, free from (ii) retinopathy treated according to local guidelines up to discharge from hospital.
Timepoint [1] 262267 0
before hospital Discharge
Secondary outcome [1] 314714 0
Brain Injury as per ANZNN definition
Timepoint [1] 314714 0
At 36 weeks corrected gestational age
Secondary outcome [2] 314715 0
Chronic lung disease as per ANZNN definition
Timepoint [2] 314715 0
At 36 weeks corrected gestational age
Secondary outcome [3] 314716 0
Necrotising enterocolitis of Grade II or higher
Timepoint [3] 314716 0
At 36 weeks corrected gestational age
Secondary outcome [4] 314717 0
Late onset sepsis as per ANZNN definition
Timepoint [4] 314717 0
at 36 weeks corrected gestational age
Secondary outcome [5] 314718 0
Retinopathy treated as per the local guidelines
Timepoint [5] 314718 0
Up to discharge
Secondary outcome [6] 327678 0
Time to full enteral feeds (greater or equal to 120ml/kg/day for 3 consecutive days).
This will be collected from medical records.
Timepoint [6] 327678 0
Up to discharge
Secondary outcome [7] 327679 0
number of blood transfusions.
This outcome will be collected from the medical records.
Timepoint [7] 327679 0
At 36 weeks gestational age
Secondary outcome [8] 327680 0
length of hospital stay.
This outcome will be collected from medical records,
Timepoint [8] 327680 0
Up to discharge
Secondary outcome [9] 327682 0
financial costs (for cost-effectiveness analysis in Australia only).
This will be collected using parent questionnaires.
Timepoint [9] 327682 0
To 36 months corrected age
Secondary outcome [10] 327683 0
long-term survival
This outcome will be collected by contact with the parents up to the follow up assessment.
Timepoint [10] 327683 0
at 24 and 36 months corrected gestational age
Secondary outcome [11] 327684 0
Survival
Timepoint [11] 327684 0
Up to discharge
Secondary outcome [12] 327685 0
long-term development outcomes.
This outcome will be collected using parent questionnaires at time of follow up.
Timepoint [12] 327685 0
at 24 and 36 months corrected gestational age

Eligibility
Key inclusion criteria
Babies are eligible if (a) <1500 g birth weight (b) less than or equal to 7 days old and expected to survive and (c) parent gives written informed consent.

Minimum age
No limit
Maximum age
7 Days
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Babies with severe congenital anomalies which are likely to cause death are not eligible

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)
Allocation concealment will be maintained by using a web-based randomisation service supported by the Trial Centre.

The study is masked, i.e. treatment allocation will be concealed from investigators, clinicians and parents. To maintain the masking, nursing staff will prepare the bLF dose or control out of site of parents or clinical staff.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
auotmated sequence generation based on the stratification variables
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
nil
Phase
Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
A sample size of 1,500 infants has 85% power at the two-sided 5% significance level to detect a difference in the proportion meeting the primary outcome assuming the true probability is 74% in controls and 80.5% in infants having bLF. The power of the trial remains above 80% even if nonadherence to randomized treatment occurs in 5% of participants. A non-adherence rate <5% is likely based on our previous tria. The estimated proportion meeting the primary outcome in the control arm is informed by pre-trial estimates, blinded (pooled) review of accumulating trial data (most recently undertaken in December 2016), and the anticipated beneficial effects of the growing use of probiotics and downward trend in rates of sepsis. A statistical analysis plan will be prepared and finalised prior to unblinding the data. All randomised subjects will be eligible for inclusion in efficacy analyses in accordance with the intention-to-treat analysis principle. Subjects will be analysed according to the regimen they actually received for comparisons on SUSAR rates. The primary analysis will be a comparison between treatment groups on the proportion experiencing the primary outcome using a chi-squared statistic that accommodates possible correlation of data between siblings from multiple births. Other binary secondary outcomes will be analysed using the same method, whilst comparable approaches applicable to continuous data will be applied as required. Estimates of the treatment effect adjusted for baseline characteristics will be calculated in sensitivity analyses using the relevant linear modelling approach. These modelling techniques will also be used to identify clinically important prognostic factors and to perform tests of heterogeneity in the subgroup analyses. Hypothesis tests will be undertaken at the two-sided 5% level of significance. P-values from secondary analyses that are unadjusted for multiple comparisons will be interpreted in proper context.
Subgroup analyses: Consistency of the treatment effect on the primary endpoint will be evaluated across the following subgroups: (i) birthweight <1000 g and 1000-1499 g; (ii) randomised =72 hr and >72 hr from birth; (iii) those who received and did not receive probiotics by 36 weeks corrected gestation; (iv) = 28 weeks and >28 weeks gestation at birth.

Recruitment
Recruitment status
Active, not 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)
ACT,NSW,QLD,SA,VIC
Recruitment outside Australia
Country [1] 8225 0
New Zealand
State/province [1] 8225 0
Christchurch; Wellington

Funding & Sponsors
Funding source category [1] 264606 0
Government body
Name [1] 264606 0
NHMRC
Address [1] 264606 0
National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601
Country [1] 264606 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
Locked Bag 77
Camperdown
NSW 2050
Country
Australia
Secondary sponsor category [1] 263746 0
None
Name [1] 263746 0
Address [1] 263746 0
Country [1] 263746 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 260606 0
Northern Sydney Local Health District HREC
Ethics committee address [1] 260606 0
Research Office, Kolling Building Level13 Royal North Shore Hospital St Leonards NSW 2065
Ethics committee country [1] 260606 0
Australia
Date submitted for ethics approval [1] 260606 0
Approval date [1] 260606 0
26/08/2010
Ethics approval number [1] 260606 0
HREC/10/HAWKE/32
Ethics committee name [2] 295944 0
Women's and Children's Health Network HREC
Ethics committee address [2] 295944 0
Level 2, Samuel Way Building; 72 King William Road
North Adelaide SA 5006
Ethics committee country [2] 295944 0
Australia
Date submitted for ethics approval [2] 295944 0
13/11/2013
Approval date [2] 295944 0
20/06/2014
Ethics approval number [2] 295944 0
HREC/13/WCHN/165
Ethics committee name [3] 295945 0
Northern B Health and Disability Ethics Committee
Ethics committee address [3] 295945 0
PO Box 5013
Wellington 6011
Ethics committee country [3] 295945 0
New Zealand
Date submitted for ethics approval [3] 295945 0
13/01/2016
Approval date [3] 295945 0
21/03/2016
Ethics approval number [3] 295945 0
16/NTB/12
Ethics committee name [4] 295946 0
ACT Health HREC
Ethics committee address [4] 295946 0
PO Box 11
Woden ACT 2601
Ethics committee country [4] 295946 0
Australia
Date submitted for ethics approval [4] 295946 0
Approval date [4] 295946 0
31/07/2014
Ethics approval number [4] 295946 0
ETH.6.14.140
Ethics committee name [5] 295947 0
Mercy Health
Ethics committee address [5] 295947 0
Level 2 Shelley Street
Richmond Vic 3121
Ethics committee country [5] 295947 0
Australia
Date submitted for ethics approval [5] 295947 0
15/03/2016
Approval date [5] 295947 0
04/07/2016
Ethics approval number [5] 295947 0
R16/19

Summary
Brief summary
A two arm randomised controlled trial in more than 1500 preterm babies less than 1500 grams to compare standard feeding regimens versus adding BLF to feeds on the incidence of death and major disability in VLBW infants.
Trial website
nil
Trial related presentations / publications
nil
Public notes

Contacts
Principal investigator
Name 32309 0
Prof William Tarnow-Mordi
Address 32309 0
NHMRC Clinical Trials Centre
Locked Bag 77
Camperdown, NSW, 1450
Country 32309 0
Australia
Phone 32309 0
+61 2 9562 5000
Fax 32309 0
Email 32309 0
lift@ctc.usyd.edu.au
Contact person for public queries
Name 15556 0
Prof William Tarnow-Mordi
Address 15556 0
NHMRC Clinical Trial Centre Locked Bag 77 Camperdown NSW 1450
Country 15556 0
Australia
Phone 15556 0
+61 2 9562 5000
Fax 15556 0
Email 15556 0
williamtm@med.usyd.edu.au
Contact person for scientific queries
Name 6484 0
Dr Alpana Ghadge
Address 6484 0
NHMRC Clinical Trial Centre Locked Bag 77 Camperdown NSW 1450
Country 6484 0
Australia
Phone 6484 0
+61 2 9562 5000
Fax 6484 0
Email 6484 0
alpana.ghadge@ctc.usyd.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary