Born early, breathe easy
| ISRCTN | ISRCTN14767962 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14767962 |
| EudraCT/CTIS number | 2015-003712-20 |
| Secondary identifying numbers | 2015-003712-20 |
- Submission date
- 08/01/2016
- Registration date
- 12/02/2016
- Last edited
- 06/03/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Neonatal Diseases
Plain English summary of protocol
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
Contact information
Scientific
Department of Child Health
School of Medicine
Cardiff University
Heath Park
Cardiff
CF144XN
United Kingdom
Scientific
Department of Child Health
School of Medicine
Cardiff University
Heath Park
Cardiff
CF1 44XN
United Kingdom
Public
North Wales Organisation for Randomised Trials in Health & Social Care)
Meirion Building
Normal Site
Bangor University
Gwynedd
Bangor
LL57 2PZ
United Kingdom
| Phone | +44 (0)1248 382442 |
|---|---|
| RHINO@bangor.ac.uk |
Study information
| Study design | Single-centre, randomised, double blind, placebo controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Community |
| Study type | Other |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| 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 |
| Study acronym | RHINO |
| Study objectives | 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(s) | South West - Central Bristol Research Ethics Committee, 26/11/2015, ref: 15/SW/0289 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | 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 study start date | 12/03/2015 |
| Completion date | 30/06/2020 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 7 Years |
| Upper age limit | 12 Years |
| Sex | Both |
| Target number of participants | 200 Randomised from approximately 1000 screened |
| Total final enrolment | 53 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 01/05/2016 |
| Date of final enrolment | 31/12/2019 |
Locations
Countries of recruitment
- United Kingdom
- Wales
Study participating centre
Cardiff
CF144XN
United Kingdom
Sponsor information
University/education
30-36 Newport Road
Cardiff
Cardiff CF24 0DE
Wales
United Kingdom
| Website | http://www.cardiff.ac.uk/racdv/resgov/contactus/index.html |
|---|---|
"ROR" |
https://ror.org/03kk7td41 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- Medical Research Council (United Kingdom), UK Medical Research Council, MRC
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 15/12/2021 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| 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. |
| IPD sharing plan | The current data sharing plans for this study are unknown and will be available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 13/12/2021 | 10/01/2022 | Yes | No | |
| Protocol file | version 10 | 16/10/2018 | 22/08/2022 | No | No |
| HRA research summary | 28/06/2023 | No | No | ||
| Statistical Analysis Plan | Trial Protocol and Statistical Analysis Plan | 06/03/2024 | No | No |
Additional files
Editorial Notes
06/03/2024: A link to the statistical analysis plan was added.
22/08/2022: Protocol file uploaded.
10/01/2022: The following changes have been made:
1. Publication reference added.
2. The final enrolment number has been added from the reference.
26/10/2021: The intention to publish date has been changed from 31/10/2021 to 15/12/2021.
23/09/2021: The intention to publish date has been changed from 31/03/2021 to 31/10/2021.
23/07/2020: The intention to publish date was changed from 31/12/2020 to 31/03/2021.
18/05/2018: A public contact has been added. The public title has been changed from "Born early, breath easy" to "Born early, breathe easy".
04/05/2018: The following changes have been made:
1. The scientific title has been changed from "Respiratory Health outcomes In NeOnates" to "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".
2. The recruitment end date has been changed from 31/12/2018 to 31/12/2019.
3. The overall trial end date has been changed from 31/12/2019 to 30/06/2020.
4. The intention to publish date has been changed from 30/06/2019 to 31/12/2020.
