Clinical trial NCT03367013: Lactoferrin Infant Feeding Trial - LIFT_Canada
Official title: Lactoferrin Infant Feeding Trial - LIFT_Canada
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Preterm Infant
Very Low Birth Weight Infant
Morbidity;Newborn
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
Collaborators: name: Sunnybrook Research Institute (Toronto, Ontario)
name: Canadian Institutes of Health Research (CIHR)
name: National Health and Medical Research Council, Australia
First posted: 2017-12-08
Enrollment: 453
Sex: ALL
Minimum age (years): 2
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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

Eligibility 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

Primary outcomes:
measure: Hospital mortality or major morbidity
timeFrame: Randomization to 36 weeks corrected gestation or to transfer/discharge if earlier.
Secondary outcomes:
measure: Incidence of all-cause in-hospital mortality
timeFrame: Randomization to 36 weeks corrected gestation or to transfer/discharge if earlier
measure: Incidence of each of the 5 components of the composite primary endpoint
timeFrame: Randomization to 36 weeks corrected gestation or to transfer/discharge if earlier
measure: Incidence of chronic lung disease at 36 weeks CG
timeFrame: Randomization to 36 weeks corrected gestation or to transfer/discharge if earlier
measure: Time to first day of full enteral feeds (≥120ml/kg/day for 3 consecutive days)
timeFrame: Randomization to 36 weeks corrected gestation or to transfer/discharge if earlier
measure: Number of blood transfusions
timeFrame: Randomization to 36 weeks corrected gestation or to transfer/discharge if earlier
measure: Length of hospital stay
timeFrame: Randomization to 36 weeks corrected gestation or to transfer/discharge if earlier
measure: Weight and head circumference at 36 weeks corrected gestation
timeFrame: Randomization to 36 weeks corrected gestation or to transfer/discharge if earlier
measure: Incidence of death by 24 months corrected age or the presence of neurodevelopmental outcomes at 24 months corrected age
timeFrame: Randomization to 36 weeks corrected gestation
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
city: Vancouver
country: Canada
facility: Children's and Women's Health Centre BC
state: British Columbia
city: Winnipeg
country: Canada
facility: Health Sciences Centre Winnipeg
state: Manitoba
city: Winnipeg
country: Canada
facility: Saint Boniface Hospital
state: Manitoba
city: Halifax
country: Canada
facility: IWK Health Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: McMaster Children's Hospital
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
affiliation: Sunnybrook Health Sciences Centre
name: Elizabeth Asztalos, MD,MSc,FRCPC
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schmidt B, Asztalos EV, Roberts RS, Robertson CM, Sauve RS, Whitfield MF; Trial of Indomethacin Prophylaxis in Preterms (TIPP) Investigators. Impact of bronchopulmonary dysplasia, brain injury, and severe retinopathy on the outcome of extremely low-birth-weight infants at 18 months: results from the trial of indomethacin prophylaxis in preterms. JAMA. 2003 Mar 5;289(9):1124-9. doi: 10.1001/jama.289.9.1124.
citation: Bassler D, Stoll BJ, Schmidt B, Asztalos EV, Roberts RS, Robertson CM, Sauve RS; Trial of Indomethacin Prophylaxis in Preterms Investigators. Using a count of neonatal morbidities to predict poor outcome in extremely low birth weight infants: added role of neonatal infection. Pediatrics. 2009 Jan;123(1):313-8. doi: 10.1542/peds.2008-0377.
citation: Schulzke SM, Deshpande GC, Patole SK. Neurodevelopmental outcomes of very low-birth-weight infants with necrotizing enterocolitis: a systematic review of observational studies. Arch Pediatr Adolesc Med. 2007 Jun;161(6):583-90. doi: 10.1001/archpedi.161.6.583.
citation: Lonnerdal B. Nutritional roles of lactoferrin. Curr Opin Clin Nutr Metab Care. 2009 May;12(3):293-7. doi: 10.1097/MCO.0b013e328328d13e.
citation: Albera E, Kankofer M. Antioxidants in colostrum and milk of sows and cows. Reprod Domest Anim. 2009 Aug;44(4):606-11. doi: 10.1111/j.1439-0531.2007.01027.x.
citation: Embleton NE, Pang N, Cooke RJ. Postnatal malnutrition and growth retardation: an inevitable consequence of current recommendations in preterm infants? Pediatrics. 2001 Feb;107(2):270-3. doi: 10.1542/peds.107.2.270.
citation: Asztalos EV, Barrington K, Lodha A, Tarnow-Mordi W, Martin A. Lactoferrin infant feeding trial_Canada (LIFT_Canada): protocol for a randomized trial of adding lactoferrin to feeds of very-low-birth-weight preterm infants. BMC Pediatr. 2020 Jan 29;20(1):40. doi: 10.1186/s12887-020-1938-0.