Lactoferrin Infant Feeding Trial - LIFT_Canada

Preterm Infant Clinical Trial

Official title:

Lactoferrin Infant Feeding Trial - LIFT_Canada

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03367013
• Other study ID #: 0890
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 16, 2018
• Est. completion date: June 30, 2024

Study information

• Verified date: August 2023
• Source: Sunnybrook Health Sciences Centre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 453
• Est. completion date: June 30, 2024
• Est. primary completion date: July 27, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Days to 7 Days

Eligibility

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

Related Conditions & MeSH terms

• Birth Weight
• Morbidity;Newborn
• Preterm Infant
• Very Low Birth Weight Infant

Intervention

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:
• 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.

Locations

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

Sponsors (3)

Lead Sponsor	Collaborator
Sunnybrook Health Sciences Centre	Canadian Institutes of Health Research (CIHR), National Health and Medical Research Council, Australia

Country where clinical trial is conducted

Canada, 

References & Publications (6)

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. — View 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. — View 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. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Incidence of all-cause in-hospital mortality		Randomization to 36 weeks corrected gestation or to transfer/discharge if earlier
Secondary	Incidence of each of the 5 components of the composite primary endpoint		Randomization to 36 weeks corrected gestation or to transfer/discharge if earlier
Secondary	Incidence of chronic lung disease at 36 weeks CG		Randomization to 36 weeks corrected gestation or to transfer/discharge if earlier
Secondary	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
Secondary	Number of blood transfusions		Randomization to 36 weeks corrected gestation or to transfer/discharge if earlier
Secondary	Length of hospital stay		Randomization to 36 weeks corrected gestation or to transfer/discharge if earlier
Secondary	Weight and head circumference at 36 weeks corrected gestation		Randomization to 36 weeks corrected gestation or to transfer/discharge if earlier
Secondary	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

External Links

•   Canadian Neonatal Network. Accessed September 30, 2016.