Morbidity;Newborn, Preterm Infant, Very Low Birth Weight Infant
Conditions
Brief summary
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
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
Interventions
DIETARY_SUPPLEMENTBovine Lactoferrin
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.
OTHERNo Bovine Lactoferrin added
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.
Sponsors
Sunnybrook Research Institute (Toronto, Ontario)
Canadian Institutes of Health Research (CIHR)
National Health and Medical Research Council, Australia
Dr. Elizabeth Asztalos
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Days to 7 Days
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hospital mortality or major morbidity | Randomization to 36 weeks corrected gestation or to transfer/discharge if earlier. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Incidence of all-cause in-hospital mortality | 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 | Randomization to 36 weeks corrected gestation | 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) |
| Number of blood transfusions | Randomization to 36 weeks corrected gestation or to transfer/discharge if earlier | — |
Countries
Canada
Outcome results
None listed