Plain English Summary
Background and study aims
This project looks at whether some babies born early can have long-term breathing problems as they go through childhood which have not yet been detected. Research on very premature babies has shown that their lungs may not work as well as babies born at, or earlier to, their due date. Work already done by the researchers of this project has also shown that some moderately premature babies are at risk of having breathing problems as they grow up. The next step of this research is to invite some families to participate in a study to look at possible reasons why children born early may have breathing problems. The researchers want to know whether there are differences in the structure and function of the airways in the children born prematurely compared to those born on time. If prematurely born children are different, they may benefit from closer follow-up and possibly some treatment to improve their breathing.
Who can participate?
Children (and families) aged between 7-12 who were born prematurely (at 34 weeks gestation or less)
What does the study involve
First of all, each child does some breathing tests (at home, if possible) and both them and their parents are asked to fill in some questionnaires about their daily life. A sample of saliva (spit) is also collected. The aim of the visit is to assess how many children have lower than expected results on the breathing test. Children will a lower than expected result are asked to take part in the next stage. For this stage, each child and their parents visit the laboratory on two occasions to have more detailed breathing tests before and after exercising on a stationary bicycle. After the first visit, each child is given an inhaler to use twice a day for 12 weeks. The type of inhaler they are given is allocated randomly and could be one containing fluticasone proprionate, a fluticasone proprionate/salmeterol xinafoate combination or a placebo (dummy inhaler). Any response to the inhaler treatment will be seen at the second visit. Finally, some children are invited to have a MRI scan of their lungs to look at how well they are working.
What are the benefits and risks?
The researchers aim to show that children born early have limitations in their lung function which may cause breathing problems. If so, they will be able to find out if treating with medicine is successful in easing the symptoms. Children born preterm have generally been ignored, however the evidence from this study may indicate to healthcare policy makers that closer follow-up is required in these children; secondly, it may indicate that treatment should be considered an option in all children born preterm, (extremely or moderately) with reduced lung function. In the future, this surveillance and treatment may reduce the burden on NHS resources in terms of GP and hospital visits. As with all medicines, there are some small risks of side effects. However these are rare and often mild.
Where is the study run from?
Children’s Hospital for Wales (UK)
When is study starting and how long is it expected to run for?
March 2015 to December 2019
Who is the main contact
Mr John Lowe
Trial website
Contact information
Type
Scientific
Primary contact
Mr John Lowe
ORCID ID
Contact details
Department of Child Health
School of Medicine
Cardiff University
Heath Park
Cardiff
CF144XN
United Kingdom
Type
Scientific
Additional contact
Prof Sailesh Kotecha
ORCID ID
Contact details
Department of Child Health
School of Medicine
Cardiff University
Heath Park
Cardiff
CF1 44XN
United Kingdom
Type
Public
Additional contact
Ms Alison Jenkins
ORCID ID
Contact details
North Wales Organisation for Randomised Trials in Health & Social Care)
Meirion Building
Normal Site
Bangor University
Gwynedd
Bangor
LL57 2PZ
United Kingdom
+44 (0)1248 382442
RHINO@bangor.ac.uk
Additional identifiers
EudraCT number
2015-003712-20
ClinicalTrials.gov number
Protocol/serial number
2015-003712-20
Study information
Scientific title
Respiratory Health Outcomes in Neonates - A randomised, double blind, double-dummy placebo-controlled trial of inhaled treatment to establish the mechanisms of prematurity-associated airway obstruction and inflammation
Acronym
RHINO
Study hypothesis
The overall aim is to establish the underlying mechanisms of chronic airway obstruction observed in symptomatic children who are born preterm and to establish if there are different phenotypes of this condition that do or do not respond to standard inhaled therapy.
Ethics approval
South West - Central Bristol Research Ethics Committee, 26/11/2015, ref: 15/SW/0289
Study design
Single-centre, randomised, double blind, placebo controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Community
Trial type
Other
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Prematurity-associated respiratory disease
Intervention
Random assignment to using one of the three following metered-dose inhalers
1. Fluticasone proprionate
2. Fluticasone proprionate/salmeterol xinafoate combination
3. Placebo
Intervention type
Drug
Phase
Phase IV
Drug names
1. Fluticasone proprionate
2. Salmeterol xinafoate
Primary outcome measure
The primary outcome will be the difference in pre and post treatment percent predicted FEV1 after 12 weeks of therapy between the active and placebo groups
Secondary outcome measures
1. Differences in measures of obstructive airway disease (pulmonary function tests)
2. Differences in response to exercise challenge between treatment groups.
3. Differences in biomarkers of airway inflammation between treatment groups
4. Differences in respiratory and neurological symptoms (questionnaire)
5. MRI parameters: apparent diffusion coefficient (ADC) between 3 comparison groups (preterm, FEV1 ≤85% at baseline; preterm control, FEV1 ±1 standard deviation from normal; and term control, FEV1 ±1 standard deviation from normal).
6. Pre- and- post treatment differences in objectively measured physical activity
7. Adverse events
All outcomes to be measured after 12 weeks of therapy between the active and placebo groups
Overall trial start date
12/03/2015
Overall trial end date
30/06/2020
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Children aged 7-12 at the time of screening
2. Born at a gestational age ≤34 weeks (NB. Approximately n=50 term controls will also be invited)
3. Resident in the south Wales area whom, in the opinion of the Investigator, are possible to follow up
4. Fully informed proxy consent from parents/guardians and assent from child where possible
Participant type
Patient
Age group
Child
Gender
Both
Target number of participants
200 Randomised from approximately 1000 screened
Participant exclusion criteria
1. Respiratory tract infection within the last three 3 weeks (will be asked to consider participating at a later date)
2. Congenital abnormalities
3. In the opinion of the Investigator have:
3.1. Severe cardiopulmonary defects, or
3.2. Neuromuscular disease, or
3.3. Severe neurodevelopmental impairment
Which prohibit the possibility of compliance with the study protocol
Recruitment start date
01/05/2016
Recruitment end date
31/12/2019
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Children's Hospital of Wales
Heath Park
Cardiff
CF144XN
United Kingdom
Sponsor information
Organisation
Cardiff University
Sponsor details
30-36 Newport Road
Cardiff
Cardiff CF24 0DE
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Government
Funder name
Medical Research Council
Alternative name(s)
MRC
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
We will publish the results in scientific journals. However we will also make our findings available on the study website in a format accessible to our participants and the wider community. we have a parent representative to support us with this dissemination.
Intention to publish date
31/12/2020
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list