Project: Childrens Oxygen Administration Strategies Trial-Nutrition

Acronym	COAST-Nutrition (Reference Number: RIA2016S-1636)
Duration	01/05/2018 - 31/10/2021
Project Topic	Pneumonia is the leading cause of mortality in children under 5 years old(1, 2). The World Health Organization recommends presumptive antibiotic treatment and oxygen for those hospitalized with clinically severe pneumonia and hypoxia(3). Yet, there is substantial evidence that current syndromic management guidelines are not working in practice resulting in high in-patient mortality (9-16%)(4, 5) and post-discharge mortality with undernutrition being the major determinate of mortality risk(6, 7). There are major gaps between current treatment policies and implementation of oxygen treatment stemming from unpredictable supplies, high costs and lack of relevant research to inform guidelines. Systematic and policy reviews indicate the need for a formal evaluation of the hypoxia threshold at which oxygen should be targeted and of how oxygen is best administered(8-10). Early and supplementary feeding to avert post-discharge mortality has been recommended but not yet tested in clinical trials. COAST is designed to address these key research gaps to provide a better evidence base for future guidelines, with a view to improving the poor global outcomes. The COAST trial aims to provide the relevant evidence for policy makers and health services by evaluating key elements of an integrated management strategy in African hospitals on the basis of clinical effectiveness and costs. COAST will simultaneously evaluate two related oxygenation strategies in 4200 children to reduce shorter-term mortality at 48-hours (primary endpoint) and longer-term morbidity and mortality to 28 days in a large Phase III trial with a factorial design: (i) liberal oxygenation (recommended care) compared with a strategy that permits hypoxia to SaO2 > or = 80% (routine care); and (ii) High flow delivery of oxygen (by AIRVO2 which provides positive airway pressure) compared with low flow delivery (routine care) reduces the work of breathing and respiratory exhaustion in hospitals that have no facilities for mechanical ventilation. COAST has received funding from Wellcome Trust-Medical Research Council, UK and requests strategic support from EDCTP to maximise the impact of the trial infrastructure we will use this platform to enrol children into a further trial (COAST-Nutrition) at 48-hours examining whether supplemented feeding to Day-28 improves 90-day survival. We also aim to evaluate whether point-of-care test and other biomarkers can predict clinical and radiologically-defined pneumonia in those with viral and bacterial aetiologies in order to refine endpoints for the COAST trial and future targeting of definitive and supportive therapies including tailoring antibiotic management in hospitals lacking microbiology services.
Network	EDCTP2
Call	Strategic actions supporting large-scale clinical trials 2016

Project partner

Number	Name	Role	Country
1	Imperial College of Science Technology and Medicine	Coordinator	United Kingdom
2	Academisch Medisch Centrum bij de Universiteit van Amsterdam	Partner	Netherlands
3	Global Health Uganda Ltd	Partner	Uganda
4	Intensive Care National Audit & Research Centre	Partner	United Kingdom
6	Mbale Regional Referral Hospital	Partner	Uganda
7	The Chancellor, the Masters and the Scholars of the University of Oxford	Partner	United Kingdom
9	University of Tampere School of Medicine	Partner	Finland