Plain English Summary
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
Trial website
Contact information
Type
Scientific
Primary contact
Prof William McGuire
ORCID ID
Contact details
Centre for Reviews and Dissemination
Hull York Medical School and University of York
York
YO10 5DD
United Kingdom
01904 321057
william.mcguire@hyms.ac.uk
Additional identifiers
EudraCT number
2012-004260-22
ClinicalTrials.gov number
Protocol/serial number
ELFIN01
Study information
Scientific title
A multi-centre randomised placebo-controlled trial of prophylactic enteral lactoferrin supplementation to prevent late-onset invasive infection in very preterm infants
Acronym
ELFIN
Study hypothesis
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
National Research Ethics Service (NRES) Committee East Midlands - Nottingham 2, Ref: 13/EM/0118, Date: 02/04/2013
Study design
Phase III multi-centre placebo-controlled randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Prevention
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
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 names
Lactoferrin
Primary outcome measure
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.
Secondary outcome measures
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
Overall trial start date
01/03/2013
Overall trial end date
31/05/2018
Reason abandoned (if study stopped)
Eligibility
Participant 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.
Participant type
Patient
Age group
Neonate
Gender
Both
Target number of participants
2200 (including pilot phase)
Participant 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
Recruitment start date
01/09/2013
Recruitment end date
28/09/2017
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Hull York Medical School and University of York
York
YO10 5DD
United Kingdom
Funders
Funder type
Government
Funder name
National Institute for Health Research (NIHR) Health Technology Assessment Programme (HTA) (ref: 10/57/14)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list