Lactoferrin Infant Feeding Trial - LIFT_Canada

Study Overview
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Brief Summary
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This is a multicentre, phase III, 2-arm, masked randomized controlled trial. The primary hypothesis is that oral bovine lactoferrin (bLF), through its antimicrobial, antioxidant and anti-inflammatory properties, will reduce the rate of mortality or major morbidity in very low birth weight (VLBW) preterm infants.

Detailed Description
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Almost 3,000 very low birth weight (VLBW), <1500g preterm infants are born and treated in Canada annually. About 1,200 either die or survive with severe brain or lung injury, retinopathy, late-onset sepsis or necrotizing enterocolitis (NEC), each of which is associated with substantial risk of childhood disability. Lactoferrin is an antimicrobial, antioxidant, anti-inflammatory iron-carrying, bifidogenic glycoprotein found in all vertebrates and in mammalian milk, leukocytes and exocrine secretions. However, most VLBW infants receive insufficient human lactoferrin (hLF) from human breast milk in the first months of life, resulting in suboptimal protection. Because hLF is expensive, bovine lactoferrin (bLF) has been considered as an alternate supplement to improve this suboptimal protection. LIFT is one of several ongoing trials using higher doses of bovine bLF in the VLBW population (120-200 mg/kg/d). If LIFT confirms a 19% reduction in the relative risk of its primary outcome, bLF will have a major impact, translating into thousands more intact survivors without major morbidity in Australia, New Zealand, Canada, Europe and worldwide each year. As >90% of very preterm survivors at hospital discharge reach adulthood, this represents more than 19,000 life-years gained in Canada alone each year, one of the largest gains in intact survival in any specialty since neonatal surfactant and antenatal steroids

Official Title
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Lactoferrin Infant Feeding Trial - LIFT_Canada

Conditions
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Preterm Infant, Very Low Birth Weight Infant, Morbidity;Newborn

Intervention / Treatment
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* Dietary Supplement: Bovine Lactoferrin
* Other: No Bovine Lactoferrin added


Participation Criteria
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Eligibility Criteria
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An infant will be able to participate once a parent or guardian has provided a written informed consent and the infants must meet all of the following inclusion criteria: <1500 g at birth 2-7 days old and not moribund infant is considered to be stable by the clinical care team has initiated feeds Any infant meeting any of the following exclusion criteria will be excluded from participation in this study severe congenital anomalies which are likely to cause death or known to contribute to an adverse neurodevelopmental outcome major congenital gastrointestinal anomalies which will prevent an early approach to feeding parents unable to provide informed consent

Ages Eligible for Study
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Minimum Age: 2 Days
Maximum Age: 7 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention Group<br>The intervention group will receive a daily dose of 200 mg/kg of bovine lactoferrin in breast/donor human milk or formula milk until 34 weeks corrected gestation or for a minimum of 2 weeks, whichever is longer, or until discharge home or transfer, if earlier. | Dietary Supplement: Bovine Lactoferrin<br>* Intervention includes a daily dose of 200 mg/kg bovine lactoferrin in breast/donor human milk or formula milk until 34 weeks corrected gestation or for a minimum of 2 weeks, whichever is longer, or until discharge home or transfer, if earlier.<br>* Other names: Lactoferrin-250;|
| Sham Comparator: Control Group<br>The control group will receive daily study feed with no bovine lactoferrin added in breast/donor human milk or formula milk until 34 weeks corrected gestation or for a minimum of 2 weeks, whichever is longer, or until discharge home or transfer, if earlier. | Other: No Bovine Lactoferrin added<br>* Control includes daily study feed with no bovine lactoferrin added in breast/donor human milk or formula milk until 34 weeks corrected gestation or for a minimum of 2 weeks, whichever is longer, or until discharge home or transfer, if earlier.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital mortality or major morbidity | Hospital mortality or major morbidity at 36 weeks corrected gestation defined as: Brain injury on ultrasound Necrotizing enterocolitis (Bell stage II or higher ) Late onset sepsis (≥ 72 hours of life, culture proven), or Retinopathy of prematurity treated according to local guidelines before discharge from hospital. | Randomization to 36 weeks corrected gestation or to transfer/discharge if earlier. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of all-cause in-hospital mortality |  | Randomization to 36 weeks corrected gestation or to transfer/discharge if earlier | 
| Incidence of each of the 5 components of the composite primary endpoint |  | Randomization to 36 weeks corrected gestation or to transfer/discharge if earlier | 
| Incidence of chronic lung disease at 36 weeks CG |  | Randomization to 36 weeks corrected gestation or to transfer/discharge if earlier | 
| Time to first day of full enteral feeds (≥120ml/kg/day for 3 consecutive days) |  | Randomization to 36 weeks corrected gestation or to transfer/discharge if earlier | 
| Number of blood transfusions |  | Randomization to 36 weeks corrected gestation or to transfer/discharge if earlier | 
| Length of hospital stay |  | Randomization to 36 weeks corrected gestation or to transfer/discharge if earlier | 
| Weight and head circumference at 36 weeks corrected gestation |  | Randomization to 36 weeks corrected gestation or to transfer/discharge if earlier | 
| Incidence of death by 24 months corrected age or the presence of neurodevelopmental outcomes at 24 months corrected age | Incidence of death by 24 months corrected age or the presence of major neurodevelopmental outcomes at 24 months corrected age, as defined: (i) visual (cannot fixate/ legally blind, or corrected acuity <6/60 in both eyes), or hearing impairment (requiring a hearing aid or cochlear implants); (ii) cerebral palsy with an inability to walk unassisted; (iii) major developmental delay involving cognition or speech (composite score < 85 for cognition or language on assessment) | Randomization to 36 weeks corrected gestation |