A COASTal view: where prior beliefs and uncertainty collide

The Children’s Oxygen Administration Strategies Trial (COAST) was an ambitious project based in Uganda and Kenya. The target population was children with severe pneumonia as assessed by presentation of peripheral oxygen saturation into two strata (hypoxaemia: SpO2 80–92% and severe hypoxaemia: SpO2 \u3c 80%). The comparisons were between high-flow humidified nasal therapy (HFNT) and standard low-flow nasal oxygen in the severe hypoxaemia stratum, but also in a fractional factorial design of more liberal oxygen use vs. permissive hypoxaemia in the less severe stratum. The primary outcome measure was mortality at 48 h. The trial was conducted by a team with an outstanding track record of delivering large pragmatic and practice-changing trials in low-income settings. We had the privilege of being independent members of the Trial Steering Committee (TSC)

Handling Oxygenation Targets in the Intensive Care Unit (HOT-ICU)-Protocol for a randomised clinical trial comparing a lower vs a higher oxygenation target in adults with acute hypoxaemic respiratory failure

Background Acutely ill adults with hypoxaemic respiratory failure are at risk of life-threatening hypoxia, and thus oxygen is often administered liberally. Excessive oxygen use may, however, increase the number of serious adverse events, including death. Establishing the optimal oxygenation level is important as existing evidence is of low quality. We hypothesise that targeting an arterial partial pressure of oxygen (PaO2) of 8 kPa is superior to targeting a PaO2 of 12 kPa in adult intensive care unit (ICU) patients with acute hypoxaemic respiratory failure. Methods The Handling Oxygenation Targets in the ICU (HOT-ICU) trial is an outcome assessment blinded, multicentre, randomised, parallel-group trial targeting PaO2 in acutely ill adults with hypoxaemic respiratory failure within 12 hours after ICU admission. Patients are randomised 1:1 to one of the two PaO2 targets throughout ICU stay until a maximum of 90 days. The primary outcome is 90-day mortality. Secondary outcomes are serious adverse events in the ICU, days alive without organ support and days alive out of hospital in the 90-day period; mortality, health-related quality-of-life at 1-year follow-up as well as 1-year cognitive and pulmonary function in a subgroup; and an overall health economic analysis. To detect or reject a 20% relative risk reduction, we aim to include 2928 patients. An interim analysis is planned after 90-day follow-up of 1464 patients. Conclusion The HOT-ICU trial will test the hypothesis that a lower oxygenation target reduces 90-day mortality compared with a higher oxygenation target in adult ICU patients with acute hypoxaemic respiratory failure.Peer reviewe