Plain English Summary
Background and study aims
Although giving oxygen is a basic element of hospital care, this treatment is costly and supplies are inadequate and erratic in African hospitals. The aim of this study is to identify which children would benefit from receiving oxygen and what would be the best delivery method.
Who can participate?
Children aged between 28 days and 12 years with a history of respiratory illness, hypoxia (lack of adequate oxygen supply) and signs of severe pneumonia (lung inflammation).
What does the study involve?
This study examines whether or not giving oxygen improves patient outcomes. For children with hypoxia, it is not certain what the best level to provide oxygen is and whether this results in a better outcome. The children with less severe hypoxia are randomly allocated to either receive oxygen or not. The children with more severe hypoxia all receive oxygen as we are more confident about the benefits of oxygen in this group. The children receiving oxygen are randomly allocated to receive oxygen either at a higher flow or at a lower flow (routine care). High flow oxygen provides extra pressure to the airways to prevent them from collapsing after every exhale. This helps reduce the effort of breathing, which is vital when lung infections can often lead to respiratory exhaustion and ultimately respiratory failure in critically sick children with limited access to relevant life support such as mechanical ventilation (the majority of hospitals in Africa).
What are the possible benefits and risks of participating?
The direct benefits to the child and/or family include:
1. Closer observation during the first 48 hours of admission, which, as a result, allows doctors and nurses to make important changes to the child’s treatment during in-hospital admission.
2. All routine non-trial medications required by the hospital to treat the child will be made available (when unavailable parents have to resort to sourcing these privately). All blood tests will be covered by the trial.
3. Reimbursement for transport cost after discharge and for follow up visits plus any treatment costs required during the visits will be made. Snacks and drinks will be provided at each follow up visit.
High flow is an accepted strategy in the management of children with respiratory failure in a multitude of countries, with few reports that it is unacceptable, so the risks of harm from this strategy are known and are extremely low.
Where is the study run from?
1. Coast Provincial General Hospital, Mombasa (Kenya)
2. KEMRI Wellcome Trust Programme (Kenya)
3. Mulago Hospital (Uganda)
4. Mbale Regional Referral Hospital (Uganda)
5. Soroti Regional Referral Hospital (Uganda)
When is the study starting and how long is it expected to run for?
December 2016 to November 2019
Who is funding the study?
Joint Global Health Trials scheme (Medical Research Council, Department for International Development and Wellcome Trust)
Who is the main contact?
1. Prof. Kathryn Maitland (k.maitland@imperial.ac.uk)
2. Mr Ayub Mpoya (AMpoya@kemri-wellcome.org)
Trial website
Contact information
Type
Scientific
Primary contact
Prof Kathryn Maitland
ORCID ID
http://orcid.org/0000-0002-0007-0645
Contact details
Wellcome Centre for Clinical Tropical Medicine
Room 232
2nd Floor
Medical School Building
St Mary's Campus
Norfolk Place
London
W2 1PG
United Kingdom
+44 (0)20 7594 3891
k.maitland@imperial.ac.uk
Type
Public
Additional contact
Mr Ayub Mpoya
ORCID ID
Contact details
KEMRI Wellcome Trust Research Programme
Clinical Trials Facility
Kilifi
PO Box 230
Kenya
+254 (0)417 522 063
AMpoya@kemri-wellcome.org
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
15IC3100
Study information
Scientific title
Children’s Oxygen Administration Strategies Trial (COAST): a randomised controlled trial of high flow versus oxygen versus control in African children with severe pneumonia
Acronym
COAST
Study hypothesis
1. To establish whether liberal oxygenation for SaO2 ≥80% will decrease mortality (at 48 hours and up to 28 days) compared with a strategy that includes permissive hypoxia (usual care)
2. To establish whether use of high flow oxygen delivery will decrease mortality (at 48 hours and up to 28 days) compared with low flow oxygen delivery (usual care)
Ethics approval
1. Imperial College, Research Ethics Committee, London, 18/08/2016, ref: 15IC3100
2. Faculty of Medicine, Research Ethics Committee Makerere University, Uganda, 29/02/2016, ref: 2016-030
3. KEMRI, Nairobi, Kenya, 31/10/2016, ref: KEMRI/RES/7/3/1
Study design
Open multicentre fractional factorial randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Severe pneumonia in African children
Intervention
The trial has two strata:
Stratum 1: severe hypoxia, SaO2 <80%); and Stratum 2: hypoxia SaO2 ≥80% and <92%).
Children in Stratum 1 (2-arm, 1:1 ratio) will all receive oxygen and randomisation will allocate participants to one of two methods of oxygen delivery:
1. High flow oxygen delivery
2. Low flow (usual practice) oxygen delivery
Children in Stratum 2 (3-arm, 2:1:1 ratio) will be allocated to:
1. Permissive hypoxia (no immediate oxygen): control
2. High flow oxygen delivery
3. Low flow oxygen delivery
The trial treatment period will last for a maximum of 48-hours post randomisation. After this time point, the participant will switch to usual care (standard clinical management). For children receiving oxygen delivered by high flow oxygen, at 48 hours, if oxygen is still required (i.e. failure to wean into room air) at this point, then the child will be switched to oxygen delivery by low flow (i.e. standard of care). During the 0-48 hour period, if a child is unable to tolerate high flow oxygen (indicated by a poor modified Comfort B (Behaviour) Scale score) and if oxygen is still required (i.e. failure to wean into room air), then the child will be switched to oxygen delivery by low flow (i.e. standard of care). If oxygen is discontinued before 48 hours e.g. hypoxia is resolved (SaO2 ≥92% measured continuously over 30 minutes) then they will switch to usual care (standard clinical management) following a successful trial of oxygen weaning.
All participants will be reassessed clinically at 1, 2, 4, 8, 12, 24 and 48 hours post-randomisation, and twice daily thereafter until discharged from hospital. All participants will then be seen at 4 weeks, and for those with suspected neurological sequelae an additional review will be done at 3 months post-randomisation. Any patient not returning for a study visit will be traced for vital status ascertainment (consent will be sought for this at recruitment).
Intervention type
Mixed
Phase
Drug names
Primary outcome measure
Mortality at 48 hours post-randomisation
Secondary outcome measures
1. Treatment failure at 48 hours
2. Survival to 28 days
3. Neurocognitive sequelae at 28 days
4. Disability-free survival to 28 days
5. Time to hypoxia (≥92%) resolution during initial hospital stay
6. Length of initial hospital stay
7. Re-admission to hospital by 28 days
8. Anthropometric status by 28 days
9. Resolution of neurocognitive sequelae at 90 days (for those with neurocognitive sequelae at 28 days)
Overall trial start date
01/12/2016
Overall trial end date
30/11/2019
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Aged between 28 days to 12 years
2. History of respiratory illness (cough, upper respiratory tract symptom or any respiratory symptoms, e.g. rapid breathing or increase work of breathing)
3. Hypoxia (pulse oximetry reading of SaO2 <92% recorded in room air over 5 minutes)
4. Plus any one of the following signs of severe pneumonia (from 2013 WHO clinical definitions for pneumonia):
4.1. Sign of respiratory distress (any one of):
4.1.1. Severe lower chest wall in-drawing
4.1.2. Use of auxiliary muscles
4.1.3. Head nodding
4.1.4. Inability to feed because of respiratory problems
4.2. Suspected pneumonia
4.2.1. Fast breathing:
4.2.1.1. Age 2–11 months: ≥ 50/minute
4.2.1.2. Age 1–5 years: ≥ 40/minute
4.2.1.3. Age 5-12 years ≥ 30/minute
4.2.2. Chest auscultation signs:
4.2.2.1. Decreased breath sounds
4.2.2.2. Bronchial breath sounds
4.2.2.3. Crackles
4.2.2.4. Abnormal vocal resonance (decreased over a pleural effusion or empyema, increased over lobar consolidation)
4.2.2.5. Pleural rub
4.3. Signs of pneumonia with a general danger sign:
4.3.1. Inability to breastfeed or drink
4.3.2. Lethargy or unconscious
4.3.3. Convulsions
Participant type
Patient
Age group
Child
Gender
Both
Target number of participants
4200
Participant exclusion criteria
1. Known uncorrected cyanotic heart disease
2. Assent/consent refusal by parent/carer
3. Previously recruited to COAST
4. Already received oxygen for this episode of illness
Recruitment start date
01/12/2016
Recruitment end date
01/12/2018
Locations
Countries of recruitment
Kenya, Uganda
Trial participating centre
Coast Provincial General Hospital
Mombasa
-
Kenya
Trial participating centre
KEMRI Wellcome Trust Programme
Kilifi District Hospital
PO Box 230
Kilifi
-
Kenya
Trial participating centre
Mulago Hospital
Department of Paediatrics
Makerere University
PO Box 7072
Kampala
-
Uganda
Trial participating centre
Mbale Regional Referral Hospital
Pallisa Road Zone
PO Box 921
Mbale
-
Uganda
Trial participating centre
Soroti Regional Referral Hospital
PO Box 289
Soroti
-
Uganda
Funders
Funder type
Research organisation
Funder name
Joint Global Health Trials scheme (Medical Research Council, Department for International Development and Wellcome Trust)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
All publications and presentations relating to the trial will be authorised by the Trial Management Group (TMG). The first publication of the trial results will be in the name of the TMG, if this does not conflict with the journal’s policy. If there are named authors, these will include the chief investigator, Trial Statistician and Trial Manager. Members of the TMG, Trial Steering Committee (TSC) and Data Monitoring Committee (DMC) and other contributors will be cited by name, if this does not conflict with the journal’s policy. Authorship of sub studies initiated outside of the TMG will be according to the individuals involved in the project but must acknowledge the contribution of the TMG. The TSC is the custodian of the data and specimens generated from the trial; trial data are not the property of individual participating investigators or health care facilities where the data were generated.
During the course and following completion of the trial there will be publications, including manuscripts and abstracts for presentations at national and international meetings, as well as the preparation of manuscripts for peer-reviewed publication. In order to avoid disputes regarding authorship, a consensus approach will be established that will provide a framework for all publications derived in full or in part from this trial. Authorship criteria will be determined using the guidelines provided by The International Committee of Medical Journal Editors.
Dissemination plans
The trialists plan to communicate throughout the course of the trial with the following audience groups: national policymakers (Ministry of Health, child health services); international policymakers (WHO, UNICEF); healthcare workers, nursing and paediatric associations, and NGOs involved in providing treatment or advocacy for children with severe respiratory diseases; academics working in related fields; communities where the trial is taking place; and organisations who provide training to healthcare workers. Engaging with key audiences will be helped by the links the trial team already have with some key stakeholders.
The trial results will be made available in a number of different formats and fora, in order to be appropriate for and accessible to different audiences. There will be face-to-face meetings; workshops; open access peer-reviewed publication; policy briefs; presentation at international conferences; press releases; lay summaries; and websites. Depending on the results films and radio programmes may also be developed and distributed; and the trialists will consult with members of the intended audiences to assess what other opportunities and tools for communicating should be used.
IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.
Intention to publish date
30/11/2020
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list
2017 protocol in: https://wellcomeopenresearch.org/articles/2-100/