Randomised controlled trial of oxygen therapy and high-flow nasal therapy in African children with pneumonia
the COAST trial group, Kathryn Maitland, Sarah Kiguli, Peter Olupot‐Olupot, Mainga Hamaluba, Karen Thomas, Florence Alaroker, R. O. Opoka, Abner Tagoola, Victor Bandika, Ayub Mpoya, Hellen Mnjella, Eva Nabawanuka, William Okiror, Margaret Nakuya, Denis Aromut, Charles Engoru, Emmanuel Oguda, T. N. Williams, John F. Fraser, David A Harrison, Kathy Rowan
Abstract
The life-saving role of oxygen therapy in African children with severe pneumonia is not yet established. The open-label fractional-factorial COAST trial randomised eligible Ugandan and Kenyan children aged > 28 days with severe pneumonia and severe hypoxaemia stratum (SpO 2 < 80%) to high-flow nasal therapy (HFNT) or low-flow oxygen (LFO: standard care) and hypoxaemia stratum (SpO 2 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. The trial was stopped early after enrolling 1852/4200 children, including 388 in the severe hypoxaemia stratum (median 7 months; median SpO 2 75%) randomised to HFNT ( n = 194) or LFO ( n = 194) and 1454 in the hypoxaemia stratum (median 9 months; median SpO 2 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 SpO 2 < 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. Respiratory support with HFNT showing potential benefit should prompt further trials.