The Children's Oxygen Administration Strategies Trial (COAST)

Abstract

Background: The life-saving role of oxygen therapy in children with clinically-defined severe pneumonia is not yet established. We hypothesised liberal oxygenation strategies and/or respiratory support may improve the high in-hospital mortality. Methods: The open-label fractional-factorial COAST trial in Ugandan and Kenyan children aged >28 days with feature of severe pneumonia. In stratum A (severe hypoxaemia: SpO2 3hours receipt of oxygen were excluded. The primary endpoint was 48-hour mortality; secondary endpoints included mortality or neurocognitive sequelae at 28 days. Findings: The Trial Steering Committee recommended halting recruitment for feasibility after 1842/4200 (44%) children enrolled. Of 1852 recruited, 388 in stratum A (median 7 months; median age SpO2 75%) were randomised to HFNT (n=194) or LFO (n=194) and 1454 in stratum B (median 9 months; median SpO2 88%) were randomised to HFNT (n=363) vs LFO (n=364) vs control (n=727). Per-protocol 109/726(15%) of controls received oxygen (when SpO2 <80%). In stratum A, 48-hour mortality was 9.3% (18/388) for HFNT vs. 13.4% (26/194) for LFO groups. In stratum B 48-mortality was 1.1% (4/363) for HFNT vs. 2.5% (9/364) LFO and 1.4% (10/727) for controls. In stratum B, adjusted (a)odds ratio (aOR) for 48-hour mortality in liberal vs permissive comparison was 1.16 (0.49-2.74;p=0.73); HFNT vs LFO comparison was 0.60 (0.33-1.06;p=0.08). Respective strata-specific 28-day mortality rates were: 18.6%(HFNT) versus 23.4%(LFO) and 3.3%(HFNT) versus 4.1%(LFO) versus 3.9%(control). Neurocognitive sequelae, assessed using Kilifi Neurodevelopmental Index, were rare in all groups. Interpretation: Conservative oxygen strategies appear safe and respiratory support with HFNT showing potential benefit should prompt further trials. Trial Registration: COAST Current Controlled Trials number, ISRCTN15622505. Funding Statement: Funded by the UK Joint Global Health Trials scheme: Medical Research Council, Department for International Development Wellcome Trust Grant Number MR/L004364/1, UK; Fisher and Paykel Healthcare (who donated the AIRVO™2 machines and oxygen interfaces for the trial). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: The ethics committees of Imperial College London, UK, Makerere University, Uganda and Kenya Medical Research Institute (KEMRI) Scientific & Ethics Review Unit, Kenya approved the protocol.