Optimisation of invasive breathing support in newborns by continuous carbon dioxide monitoring

ISRCTN ISRCTN12331315
DOI https://doi.org/10.1186/ISRCTN12331315
Secondary identifying numbers 39771
Submission date
29/10/2018
Registration date
01/11/2018
Last edited
18/10/2022
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Respiratory
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Background and study aims
Many prematurely born infants, and a small number of those born at term, will require help with their breathing in the newborn period. A breathing tube connected to a ventilator (mechanical ventilation) can be life saving, but unfortunately it can be associated with long-term complications. The most common of these adverse outcomes is chronic lung disease, yet infants can also have neurological problems at follow up and may develop cerebral palsy. These complications are increased in infants who have suffered abnormalities in their carbon dioxide levels. Therefore, if we are to improve the outcomes of infants requiring breathing support in the newborn period, it is vital that we can appropriately and safely monitor these levels. By having a real time continuous reading of carbon dioxide we aim to be able to reduce the number of acute complications of respiratory support by allowing earlier detection of blocked or dislodged breathing tubes. We also aim to be able to reduce the number of invasive blood tests performed, which would normally be used to monitor carbon dioxide levels when continuous monitoring is not available. Finally by having continual monitoring of carbon dioxide levels available we aim to be able to regulate these values more closely to avoid levels that are either too high, or too low, the results of which may lead to the adverse outcomes mentioned above.

Who can participate?
Newborns requiring invasive mechanical ventilation within the newborn period

What does the study involve?
The research team will be approaching parents within the first day of admission to the neonatal unit to discuss the study and obtain informed written consent if parents wish for their baby to take part. The study will involve inserting a small CE marked device into the routine ventilator circuit so that the levels of carbon dioxide produced can be continuously monitored.

What are the possible benefits and risks of participating?
This device is aimed at improving newborn safety whilst infants are receiving life saving breathing support, therefore participants may benefit from the use of this device. As this study is non invasive and uses a CE trademarked device, there are no known risks to participants taking part.

Where is the study run from?
King’s College Hospital Neonatal Unit, London (UK)

When is the study starting and how long is it expected to run for?
October 2018 to December 2021

Who is funding the study?
1. The Charles Wolfson Charitable Trust (UK)
2. SLE Ltd (UK)

Who is the main contact?
Professor Anne Greenough
anne.greenough@kcl.ac.uk

Contact information

Prof Anne Greenough
Scientific

4th Floor Golden Jubilee Wing
King's College Hospital
Denmark Hill
London
SE5 9RS
United Kingdom

ORCiD logoORCID ID 0000-0002-8672-5349
Phone +44 (0)20 3299 3037
Email anne.greenough@kcl.ac.uk

Study information

Study designInterventional non-randomised study
Primary study designInterventional
Secondary study designNon randomised study
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details to request a patient information sheet
Scientific titleOptimising mechanical ventilation in newborns using capnography
Study objectives1. Using end tidal capnography will allow earlier detection of acute complications in mechanically ventilated infants such as blocked or dislodged endotracheal tubes.
2. End tidal capnography will reduce the average daily frequency of invasive blood sampling and hence the associated complications related to blood transfusions.
3. Using side stream capnography to provide continuous monitoring will reduce the time spent with abnormal carbon dioxide levels and the development of serious complications such as bronchopulmonary dysplasia, intraventricular haemorrhage and periventricular leukomalacia.
4. Accurate calculation of anatomical and alveolar dead space in infants with various neonatal respiratory diseases using real time capnography will allow appropriate tidal volumes to be delivered in different respiratory conditions.
Ethics approval(s)Approved 14/11/2018, London-Camden & Kings Cross Research Ethics Committee (NHSBT Newcastle Blood Donor Centre, Holland Drive, Newcastle upon Tyne, NE2 4NQ; 0207 104 8018; nrescommittee.london-camdenandkingscross@nhs.net) ref: 18/LO/1602
Health condition(s) or problem(s) studiedMechanical ventilation in newborns
InterventionA side stream capnograph will be integrated with the ventilator circuit for the whole time the infant is receiving invasive mechanical ventilation. In order to validate the side steam capnography against the gold standard mainstream capnography, the NM3 mainstream capnograph will be incorporated into the ventilator circuit for a 20 minute period.
Infants will have routine neonatal follow up as per the clinical team and no follow up specific to the research being carried out is required.
Intervention typeDevice
Pharmaceutical study type(s)
Phase
Drug / device / biological / vaccine name(s)
Primary outcome measureDecrease in the complications of mechanical ventilation and decrease in the frequency of blood sampling in ventilated newborn infants.; Timepoint(s): .
The following are recorded throughout the period the infant is receiving invasive mechanical ventilation:
1. Frequency of complications of mechanical ventilation (pneumothorax, blocked or dislodged endotracheal tube, hypo or hypercarbia),
2. Frequency of routine blood gas sampling
These will be compared to historical controls who were invasively mechanically ventilated prior to the use of routine end tidal capnography monitoring.
Secondary outcome measures1. Validation of side stream capnography with mainstream capnography and arterial carbon dioxide levels, ascertained by correlation of values in kPa during a twenty-minute validation period
2. Anatomical and alveolar dead space, calculated in mechanically ventilated infants with four neonatal respiratory conditions:
2.1. Respiratory distress syndrome
2.2. Evolving bronchopulmonary dysplasia
2.3. Meconium aspiration syndrome
2.4. Persistent pulmonary hypertension of the newborn
These will be calculated by analysing carbon dioxide waveforms using the Bohr/Enghoff equation once the infant is no longer receiving mechanical ventilation.
Overall study start date01/10/2018
Completion date31/12/2021

Eligibility

Participant type(s)Patient
Age groupNeonate
SexBoth
Target number of participantsPlanned Sample Size: 200; UK Sample Size: 200
Total final enrolment92
Key inclusion criteria1. Neonates
2. Invasively mechanically ventilated
3. Admitted to the neonatal intensive care unit
4. Written parental consent
Key exclusion criteria1. Non ventilated infants
2. Infants on non-invasive respiratory support
Date of first enrolment28/11/2018
Date of final enrolment14/12/2021

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

Neonatal Intensive Care Unit
4th Floor Golden Jubilee Wing
King's College Hospital
Denmark Hill
London
SE5 9RS
United Kingdom

Sponsor information

King's College Hospital
Hospital/treatment centre

R&D Manager
King's College Hospital NHS Foundation Trust
161 Denmark Hill
London
SE5 8EF
England
United Kingdom

Phone +44 (0)20 3299 3841
Email Kch-tr.research@nhs.net
King's College London
University/education

Director of Research Management and Directory of Administration
King's College London
Room 5.31
57 Waterloo Road
London
SE1 8WA
England
United Kingdom

Phone +44 (0)207 848 3224
Email susan.dickson@kcl.ac.uk

Funders

Funder type

Charity

Charles Wolfson Charitable Trust

No information available

SLE LIMITED

No information available

Results and Publications

Intention to publish date31/08/2022
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryData sharing statement to be made available at a later date
Publication and dissemination planPlanned publication in a high-impact peer-reviewed journal. Results are intended to be published one year after the completion of the trial. Results will also be presented at national and international conferences.
IPD sharing planThe datasets analysed will be expected to be included in the subsequent results publication but full data sharing plans for the current study are not currently known and will be made available at a later date.

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article 01/06/2020 25/01/2022 Yes No
Results article 18/02/2021 25/01/2022 Yes No
Results article 01/07/2021 25/01/2022 Yes No
Protocol file version 1 06/08/2018 18/10/2022 No No
HRA research summary 28/06/2023 No No

Additional files

35899 Protocol v1 06Aug18.pdf

Editorial Notes

18/10/2022: Uploaded protocol (not peer-reviewed) as an additional file.
25/01/2022: Publication references added.
22/12/2021: The following changes were made to the trial record:
1. The total final enrolment was added.
2. The recruitment end date was changed from 31/12/2021 to 14/12/2021.
16/11/2021: The recruitment end date was changed from 30/11/2021 to 31/12/2021.
13/07/2021: The recruitment end date 01/07/2021 to 30/11/2021.
12/07/2021: The overall trial end date was changed from 31/08/2021 to 31/12/2021.
04/08/2020: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/07/2020 to 01/07/2021.
2. The overall end date was changed from 31/08/2020 to 31/08/2021.
3. The intention to publish date was changed from 31/08/2021 to 31/08/2022.
4. The plain English summary was updated to reflect these changes.
17/07/2019: The ethics approval was added.
25/03/2019: The condition has been changed from "Specialty: Children, Primary sub-specialty: Neonatal; Health Category: Respiratory" to "Mechanical ventilation in newborns" following a request from the NIHR.
28/11/2018: The recruitment start date has been changed from 14/11/2018 to 28/11/2018.
02/11/2018: Internal review.