A study looking at how effective and safe a very low dose of dexamethasone is in helping ventilator-dependent preterm babies who are at high risk of bronchopulmonary dysplasia (a serious lung condition that affects infants) get off the ventilator more quickly and effectively
| ISRCTN | ISRCTN81191607 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN81191607 |
| EudraCT/CTIS number | 2015-005342-63 |
| Secondary identifying numbers | 31350 |
- Submission date
- 01/08/2016
- Registration date
- 01/08/2016
- Last edited
- 19/12/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Respiratory
Plain English Summary
Background and study aims
Many premature babies are at risk of developing breathing problems because their lungs are not fully matured when they are born, and may require breathing support through a breathing tube (ventilation) at the start of life. Babies who receive prolonged breathing support are at risk of developing a lung condition called bronchopulmonary dysplasia (BPD, sometimes called chronic lung disease). This is caused, in part, by inflammation (swelling) of the baby’s developing lungs, which is likely made worse by the ventilator. When this happens, the baby needs more oxygen and may have difficulty breathing, which can take some time to improve. Babies with BPD generally stay in hospital longer and are more likely to have issues with their brain development, which affects them as they grow up. Currently, many babies who require prolonged ventilation and are at high risk of developing BPD are treated with dexamethasone, a steroid that is used in many conditions to reduce inflammation in the body. In the past, doctors used to use high doses of dexamethasone to get babies off ventilators. These high doses did work, as the babies came off the ventilators earlier and had fewer lung problems, but there were side effects. The dose being used in this study is ten times lower than the usual dose of dexamethasone. This dose appears to be effective and seems to cause fewer side effects. The aim of this study is to find out if this reduced dose, ‘minidex’, is helpful, harmful or makes no difference to the outcomes of these babies.
Who can participate?
Babies who were born more than 10 weeks early, who require prolonged ventilation and are aged between 10 and 24 days old.
What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group receive dexamethasone through a drip everyday for ten days and then every other day for a further six days. The dose given is calculated using the weight of the infants at the start of the study. Those in the second group receive a placebo (dummy), which is made up of saline (salt water) everyday for ten days and then every other day for a further six days. Participants in both groups are closely monitored and the length of time until the breathing tube is removed (extubation) is recorded.
What are the possible benefits and risks of participating?
All babies will benefit from being monitored very closely throughout the study by the staff on the Neonatal Intensive Care or Special Care Unit. There are no notable risks involved with participating in this study, as the dose of dexamethasone used is ten times lower than the standard dose and so it is unlikely that babies will suffer any side effects.
Where is the study run from?
Leeds General Infirmary (lead centre) and nine other neonatal units across the Midlands and North of England (UK)
When is study starting and how long is it expected to run for?
November 2015 to November 2018
Who is funding the study?
National institute for Health Research (UK)
Who is the main contact?
Ms Vaneesha Short
minidex@npeu.ox.ac.uk
Contact information
Public
National Perinatal Epidemiology Unit (NPEU)
Nuffield Department of Population Health
University of Oxford
Old Road Campus
Headington
Oxford
OX3 7LF
United Kingdom
| Phone | +44 (0)1865 289737 |
|---|---|
| minidex@npeu.ox.ac.uk |
Study information
| Study design | Randomised; Interventional; Design type: Treatment, Drug |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | https://www.npeu.ox.ac.uk/minidex/parent-resources |
| Scientific title | Minidex: The efficacy and safety of very low dose dexamethasone used to facilitate the extubation of ventilator dependent preterm babies who are at high risk of bronchopulmonary dysplasia |
| Study acronym | Minidex |
| Study hypothesis | The aim of this study is to determine if treatment with very low dose dexamethasone facilitates the extubation of ventilator dependent preterm babies of less than 30 weeks’ gestation who are at high risk of developing bronchopulmonary dysplasia (BPD). |
| Ethics approval(s) | North West – Liverpool Central Research Ethics Committee, 21/06/2016, ref: 16/NW/0396 |
| Condition | Specialty: Children, Primary sub-specialty: Neonatal; UKCRC code/ Disease: Reproductive Health and Childbirth/ Other disorders originating in the perinatal period |
| Intervention | Babies will be randomised in the ratio 1:1 to receive either very low dose dexamethasone or a matched placebo. Randomisation will be managed via a secure web-based randomisation facility hosted by the NPEU CTU, University of Oxford, with telephone backup available at all times (24/7, 365 days a year). The randomisation program will use a minimisation algorithm to ensure balance between the groups with respect to collaborating hospital, sex, multiple births, gestational age at birth and existing diuretic therapy for the 24 hours prior to randomisation. Intervention arm: Participants receive daily intravenous infusions of 50 mcg/kg Dexamethasone for 10 days then alternate days for 6 days. Dose to be calculated on working weight at trial entry; can be increased in line with working weight as per local practice. Control arm: Participants receive daily intravenous infusions of 50 mcg/kg placebo (0.9% saline solution) for 10 days then alternate days for 6 days. Dose to be calculated on working weight at trial entry; can be increased in line with working weight as per local practice. All participants will be followed up for safety outcomes and other outcomes until 36 weeks postmenstrual age (PMA) or discharge if sooner. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Dexamethasone |
| Primary outcome measure | Time to first extubation after randomisation when the baby remains extubated for more than 24 hours is determined using an intubation log recording times of extubations and re-intubations which will be maintained throughout the intervention period (16 days). |
| Secondary outcome measures | 1. Time to first extubation (whether or not more than 24 hours) is measured using the intubation log maintained throughout the intervention period (16 days) 2. Extubation by day 7 after randomisation (where the baby has remained extubated for more than 24 hours) is measured using the intubation log maintained throughout the intervention period (16 days) 3. Extubation by day 7 after randomisation (whether or not for more than 24 hours) is measured using the intubation log maintained throughout the intervention period (16 days) 4. Survival to 36 weeks’ postmenstrual age (or discharge if sooner) is measured using medical record review at 36 weeks’ postmenstrual age 5. Respiratory morbidity to 36 weeks’ postmenstrual age (or discharge home if sooner) is measured by medical record review at 36 weeks’ postmenstrual age (or discharge if sooner) 6. Inflammatory cytokine profile in blood and endotracheal tube secretion fluid is measured from endotracheal tube secretions and blood samples taken at baseline, 4, 7, 10 and 14 days after randomisation 7. Parent/family experience is measured using a parent-completed Diary of Care at maintained throughout the intervention period (16 days) Safety outcomes: 1. Hypertension is reported from medical record review at 36 weeks’ postmenstrual age (or discharge if sooner) 2. Hyperglycaemia is reported from medical record review at 36 weeks’ postmenstrual age (or discharge if sooner) 3. Confirmed/suspected sepsis is reported from medical record review at 36 weeks’ postmenstrual age (or discharge if sooner) 4. Spontaneous gastrointestinal perforation or NEC is reported from medical record review at 36 weeks’ postmenstrual age (or discharge if sooner) 5. Deterioration in cranial ultrasound findings (new finding of severe intraventricular haemorrhage or periventricular leukomalacia) between the cranial ultrasound scan performed prior to randomisation and cranial ultrasound scan performed at 36 weeks’ postmenstrual age (or discharge if sooner) 6. Growth measured through change in weight standard deviation score between weight measured at trial entry and day 14 7. Growth measured through change in weight standard deviation score between weight measured at day 14 and medical record review at 36 weeks’ postmenstrual age (or discharge if sooner) 8. Growth measured through change in head circumference standard deviation score between medical record review at trial entry and at 36 weeks’ postmenstrual age (or discharge if sooner) |
| Overall study start date | 01/11/2015 |
| Overall study end date | 30/11/2018 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Neonate |
| Sex | Both |
| Target number of participants | Planned Sample Size: 94; UK Sample Size: 94 |
| Total final enrolment | 22 |
| Participant inclusion criteria | 1. Born at <30 weeks’ gestation 2. Aged between 10 and 24 postnatal days (≥10 and ≤24) 3. At high risk of developing BPD: receiving mechanical ventilation via endotracheal tube (ET) with at least 30% inspired oxygen when the positive end expiratory pressure (PEEP) is at least 4 cm water and, in the opinion of the treating physician, unlikely to be extubated within 48 hours 4. Receiving caffeine therapy 5. Written informed parental consent Parents of babies recruited at Leeds Teaching Hospitals and Bradford Royal Infirmary will be asked to consent to their baby having samples taken for cytokine estimation. This will allow modelling of their inflammatory networks |
| Participant exclusion criteria | 1. Previously received postnatal steroid treatment for respiratory disease 2. No realistic prospect of survival 3. Severe congenital anomaly affecting the lungs, heart or central nervous system 4. Previous surgical abdominal procedure 5. Concurrent illness for which postnatal corticosteroid would be contra-indicated (e.g. active fungal infection, confirmed or suspected acute sepsis and acute NEC/focal intestinal perforation) 6. Participation in another trial that would preclude baby from inclusion in Minidex |
| Recruitment start date | 01/11/2016 |
| Recruitment end date | 14/04/2018 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Great George Street
Leeds
LS1 3EX
United Kingdom
Duckworth Lane
Bradford
BD9 6RJ
United Kingdom
Hardwick Road
Stockton-on-Tees
TS19 8PE
United Kingdom
Sharoe Green Lane North
Preston
PR2 9HT
United Kingdom
Mindelsohn Way
Birmingham
Birmingham
United Kingdom
Infirmary Square
Leicester
LE1 5WW
United Kingdom
Queen Victoria Road
City Newcastle upon Tyne
NE1 4LP
United Kingdom
Glossop Road
Sheffield
S10 2JF
United Kingdom
Crown Street
Liverpool
L8 7SS
United Kingdom
Clifford Bridge Road
Coventry
CV2 2DX
United Kingdom
Anlaby Road
Hull
HU3 2JZ
United Kingdom
Sponsor information
Hospital/treatment centre
Research Support Office
2nd Floor Block D Waterhouse Building
3 Brownlow Street
Liverpool
L69 3GL
England
United Kingdom
"ROR" |
https://ror.org/04xs57h96 |
|---|
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 30/11/2019 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication of study results in a high-impact peer reviewed journal. |
| IPD sharing plan | Selected results are uploaded on to the EudraCT database as per CTIMP requirements. Datasets will be made available via NPEU data sharing agreement. Applications to be made to NPEU CTU, University of Oxford, Old Road Campus, Oxford, OX3 7LF, tel: 01865 289700, email ctu@npeu.ox.ac.uk. Aggregated results reported in results publication. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/08/2019 | 19/12/2019 | Yes | No |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
19/12/2019: The following changes have been made:
1. Publication reference added.
2. The total final enrolment number has been added.
24/07/2018: IPD sharing statement added.
23/07/2018: The following changes were made to the trial record:
1. The recruitment end date was changed from 30/04/2018 to 14/04/2018.
2. The overall trial end date was changed from 30/12/2018 to 30/11/2018.
3. The intention to publish date was changed from 30/12/2019 to 30/11/2019.
31/10/2017: Internal review.
04/10/2016: Verified study information with principal investigator.
