Enteral LactoFerrin In Neonates

ISRCTN	ISRCTN88261002
DOI	https://doi.org/10.1186/ISRCTN88261002
Clinical Trials Information System (CTIS)	2012-004260-22
Protocol serial number	ELFIN01
Sponsor	University of Oxford (UK)
Funder	National Institute for Health Research (NIHR) Health Technology Assessment Programme (HTA) (ref: 10/57/14)

Submission date: 05/06/2013
Registration date: 13/06/2013
Last edited: 14/01/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Digestive System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
About 20% of very preterm infants (born before 32 weeks) acquire a serious infection. These infants are more likely to develop other problems including severe lung and bowel conditions, and have a higher risk of dying or being disabled. Better methods of preventing infection in very preterm infants are needed. This study will test whether giving them supplemental lactoferrin (a natural antibiotic protein from cow's milk) reduces the number of serious infections.

Who can participate?
We will invite participation from 2,200 very preterm infants (<32 weeks) cared for in neonatal units across the UK.

What does the study involve?
Parents will be offered information about the study and will have 72 hours to consider and give their informed consent. Infants will be randomly allocated to receive either lactoferrin or placebo (dummy) mixed with their milk. Neither doctors nor parents will be aware of what supplement the infants will receive. Treatment will continue until the infants are no longer at high risk of acquiring serious infections. As well as comparing serious infection rates between the two groups, we will also assess what effects this supplement has on the risk of other serious diseases and death, on the need for infants to receive multiple or prolonged courses of antibiotics and on the length of hospital stay.

What are the possible benefits and risks of participating?
There will be no immediate direct benefit to those taking part in the study. However, there should be benefits to future very preterm babies as the results of the study are likely to influence the NHS policy and practice.

Where is the study run from?
The study is run from the National Perinatal Epidemiology Unit Clinical Trials Unit, at the University of Oxford, UK.

When is the study starting and how long is it expected to run for?
Recruitment will start with six centres in the North of England, as part of a planned 9-month pilot, in September 2013. Following this, the study will be opened in further centres in England, Scotland and Northern Ireland and continue to recruit for a further three years.

Who is funding the study?
The National Institute for Health Research's Health Technology Assessment Programme (NIHR HTA)
has provided the funding for the study.

Who is the main contact?
Chief Investigator, Professor William McGuire: William.McGuire@hyms.ac.uk
Trial Co-ordinator, James Griffiths: james.griffiths@npeu.ox.ac.uk

Contact information

Prof William McGuire
Scientific

Centre for Reviews and Dissemination
Hull York Medical School and University of York
York
YO10 5DD
United Kingdom

Phone	01904 321057
Email	william.mcguire@hyms.ac.uk

Study information

Primary study design	Interventional
Study design	Phase III multi-centre placebo-controlled randomised controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	A multi-centre randomised placebo-controlled trial of prophylactic enteral lactoferrin supplementation to prevent late-onset invasive infection in very preterm infants
Study acronym	ELFIN
Study objectives	It is hypothesised that the proportion of very preterm (<32 weeks postmenstrual age) infants with at least one episode of late-onset invasive infection by the time of discharge from hospital will be lower in the lactoferrin group versus the placebo group
Ethics approval(s)	National Research Ethics Service (NRES) Committee East Midlands - Nottingham 2, Ref: 13/EM/0118, Date: 02/04/2013
Health condition(s) or problem(s) studied	Preterm infants, necrotising enterocolitis, late-onset invasive infection, lactoferrin
Intervention	Infants will be randomly allocated to receive either lactoferrin (150 mg/kg/day to a maximum of 300 mg) or placebo. Until discharge they will be monitored for late-onset invasive infection, necrotising enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, length of hospital stay and length of time in intensive care.
Intervention type	Drug
Phase	Phase III
Drug / device / biological / vaccine name(s)	Lactoferrin
Primary outcome measure(s)	The incidence of microbiologically-confirmed or clinically suspected late-onset infection from trial entry until hospital discharge. Clinicians will record whether or not infants have been treated for late-onset infection on the data collection form, however we are not recording specific test results.
Key secondary outcome measure(s)	1. All-cause mortality prior to hospital discharge 2. Necrotising enterocolitis (NEC): Bell's stage II or III 3. Severe retinopathy of prematurity (ROP) treated medically or surgically 4. Bronchopulmonary dysplasia (BPD): infant is still receiving mechanical ventilator support or supplemental oxygen at 36 weeks' postmenstrual age 5. A composite of invasive infection, major morbidity (NEC, ROP, or BPD as defined above) and mortality 6. Total number of days of administration of antibiotics per infant from 72 hours until death or discharge from hospital 7. Total number of days of administration of antifungal agents per infant 8. Total length of stay until discharge home 9. Length of stay in (i) intensive care, (ii) high dependency care, (iii) special care
Completion date	31/05/2018

Eligibility

Participant type(s)	Patient
Age group	Neonate
Sex	All
Target sample size at registration	2200
Key inclusion criteria	Infants will be eligible to participate if: 1. Gestational age at birth is less than 32 weeks 2. Less than 72 hours old 3. Written informed parental consent is obtained If infants are receiving antibiotic treatment for suspected or confirmed Infection, they are still eligible for recruitment.
Key exclusion criteria	1. Infants with severe congenital anomalies 2. Anticipated enteral fasting of more than 14 days 3. Infants who, in the opinion of the treating clinician, have no realistic prospect of survival
Date of first enrolment	01/09/2013
Date of final enrolment	28/09/2017

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Hull York Medical School and University of York

York
YO10 5DD
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/12/2018		Yes	No
Results article	results	02/02/2019		Yes	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Editorial Notes

14/01/2019: Publication reference added.
02/01/2019: Publication reference added.
22/01/2018: Recruitment end date was changed from 01/12/2017 to 28/09/2017. The overall trial end date was changed from 01/12/2017 to 31/05/2018.