biostudies-literatureMaitland KEuropean &#x26; Developing Countries Clinical Trials PartnershipEuropean & Developing Countries Clinical Trials Partnership (EDCTP)Medical Research CouncilWellcome Trust566-576https://www.ebi.ac.uk/biostudies/studies/S-EPMC8098782biostudies-literatureUnknown47(5)<h4>Purpose</h4>The life-saving role of oxygen therapy in African children with severe pneumonia is not yet established.<h4>Methods</h4>The open-label fractional-factorial COAST trial randomised eligible Ugandan and Kenyan children aged > 28 days with severe pneumonia and severe hypoxaemia stratum (SpO₂ < 80%) to high-flow nasal therapy (HFNT) or low-flow oxygen (LFO: standard care) and hypoxaemia stratum (SpO₂ 80-91%) to HFNT or LFO (liberal strategies) or permissive hypoxaemia (ratio 1:1:2). Children with cyanotic heart disease, chronic lung disease or > 3 h receipt of oxygen were excluded. The primary endpoint was 48 h mortality; secondary endpoints included mortality or neurocognitive sequelae at 28 days.<h4>Results</h4>The trial was stopped early after enrolling 1852/4200 children, including 388 in the severe hypoxaemia stratum (median 7 months; median SpO₂ 75%) randomised to HFNT (n = 194) or LFO (n = 194) and 1454 in the hypoxaemia stratum (median 9 months; median SpO₂ 88%) randomised to HFNT (n = 363) vs LFO (n = 364) vs permissive hypoxaemia (n = 727). Per-protocol 15% of patients in the permissive hypoxaemia group received oxygen (when SpO₂ < 80%). In the severe hypoxaemia stratum, 48-h mortality was 9.3% for HFNT vs. 13.4% for LFO groups. In the hypoxaemia stratum, 48-h mortality was 1.1% for HFNT vs. 2.5% LFO and 1.4% for permissive hypoxaemia. In the hypoxaemia stratum, adjusted odds ratio for 48-h 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). Strata-specific 28 day mortality rates were, respectively: 18.6, 23.4 and 3.3, 4.1, 3.9%. Neurocognitive sequelae were rare.<h4>Conclusions</h4>Respiratory support with HFNT showing potential benefit should prompt further trials.Intensive care medicineRandomised controlled trial of oxygen therapy and high-flow nasal therapy in African children with pneumonia.PMC8098782RIA2016S-1636MR/L004364/1202800/Z/16/ZEDCTP_RIA2016S-1636Odit AOlupot-Olupot PMolyneux EBandika VSemple CMpoya AMacharia WOpoka ROFraser JFThomas KNabawanuka EPeto TKiguli STagoola AMusoke PCOAST trial groupPeters MOkiror WTurnbull AAromut DLubega IMnjella HEngoru CHarrison DANakuya MTodd JOguda EAlaroker FRowan KWilliams TNCrawley JMaitland KWere FHamaluba MfalseRandomised controlled trial of oxygen therapy and high-flow nasal therapy in African children with pneumonia.<h4>Purpose</h4>The life-saving role of oxygen therapy in African children with severe pneumonia is not yet established.<h4>Methods</h4>The open-label fractional-factorial COAST trial randomised eligible Ugandan and Kenyan children aged > 28 days with severe pneumonia and severe hypoxaemia stratum (SpO₂ < 80%) to high-flow nasal therapy (HFNT) or low-flow oxygen (LFO: standard care) and hypoxaemia stratum (SpO₂ 80-91%) to HFNT or LFO (liberal strategies) or permissive hypoxaemia (ratio 1:1:2). Children with cyanotic heart disease, chronic lung disease or > 3 h receipt of oxygen were excluded. The primary endpoint was 48 h mortality; secondary endpoints included mortality or neurocognitive sequelae at 28 days.<h4>Results</h4>The trial was stopped early after enrolling 1852/4200 children, including 388 in the severe hypoxaemia stratum (median 7 months; median SpO₂ 75%) randomised to HFNT (n = 194) or LFO (n = 194) and 1454 in the hypoxaemia stratum (median 9 months; median SpO₂ 88%) randomised to HFNT (n = 363) vs LFO (n = 364) vs permissive hypoxaemia (n = 727). Per-protocol 15% of patients in the permissive hypoxaemia group received oxygen (when SpO₂ < 80%). In the severe hypoxaemia stratum, 48-h mortality was 9.3% for HFNT vs. 13.4% for LFO groups. In the hypoxaemia stratum, 48-h mortality was 1.1% for HFNT vs. 2.5% LFO and 1.4% for permissive hypoxaemia. In the hypoxaemia stratum, adjusted odds ratio for 48-h 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). Strata-specific 28 day mortality rates were, respectively: 18.6, 23.4 and 3.3, 4.1, 3.9%. Neurocognitive sequelae were rare.<h4>Conclusions</h4>Respiratory support with HFNT showing potential benefit should prompt further trials.2021-01-01T00:00:00Z2021 May2024-02-15T08:22:58.853Z2022-02-10T13:34:17.735ZS-EPMC80987823395483910.1007/s00134-021-06385-3