Condition category
Infections and Infestations
Date applied
13/02/2016
Date assigned
20/02/2016
Last edited
14/11/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

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 measures

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

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

Sponsor information

Organisation

Imperial College, London (UK)

Sponsor details

AHSC Joint Research Compliance Office

5th Floor Lab Block
Charing Cross Hospital
Fulham Palace Road
London
W6 8RF
United Kingdom

Sponsor type

University/education

Website

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
We 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 our different audiences. We will use 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 we may also develop and distribute films and radio programmes; and will consult with members of our intended audiences to assess what other opportunities and tools for communicating we should use.

Intention to publish date

30/11/2020

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

14/11/2016: Democratic Republic of Congo was removed from the countries of recruitment.