Lactoferrin Infant Feeding Trial - LIFT_Canada

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Morbidity;Newborn; Preterm Infant; Very Low Birth Weight Infant
• Intervention / Treatment: Dietary supplement: Bovine Lactoferrin; Other: No Bovine Lactoferrin added

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

• Study Type: Interventional
• Enrollment (Actual): 453
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Foothills Medical Centre
  • British Columbia
    • Vancouver, British Columbia, Canada
      • Children's and Women's Health Centre BC
  • Manitoba
    • Winnipeg, Manitoba, Canada
      • Health Sciences Centre Winnipeg
    • Winnipeg, Manitoba, Canada
      • Saint Boniface Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada
      • IWK Health Centre
  • Ontario
    • Hamilton, Ontario, Canada
      • McMaster Children's Hospital
    • Ottawa, Ontario, Canada
      • The Ottawa Hospital
    • Toronto, Ontario, Canada
      • Mount Sinai Hospital
    • Toronto, Ontario, Canada
      • Sunnybrook Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 days to 1 week (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Group; 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; 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.; Other Names: Lactoferrin-250
Sham Comparator: Control Group; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Collaborators: National Health and Medical Research Council, Australia; Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Elizabeth Asztalos, MD,MSc,FRCPC, Sunnybrook Health Sciences Centre

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• Lonnerdal B. Nutritional roles of lactoferrin. Curr Opin Clin Nutr Metab Care. 2009 May;12(3):293-7. doi: 10.1097/MCO.0b013e328328d13e.
• 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.
• 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.
• 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.

Helpful Links

• Canadian Neonatal Network. Accessed September 30, 2016.

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2018
• Primary Completion (Actual): July 27, 2022
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: December 4, 2017
• First Submitted That Met QC Criteria: December 4, 2017
• First Posted (Actual): December 8, 2017

Study Record Updates

• Last Update Posted (Actual): August 18, 2023
• Last Update Submitted That Met QC Criteria: August 15, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Body Weight; Birth Weight; Anti-Infective Agents; Lactoferrin
• Other Study ID Numbers: 0890

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No