MICA: Children's Oxygen Administration Strategies Trial

儿童氧气管理策略试验(STATE)是一项多中心随机对照试验，旨在确定哪些因疑似肺炎而入院的血液含氧量较低(称为缺氧)的儿童将受益于氧气，以及氧气最好的输送方式是低流量(常规护理)还是高流量。尽管氧气是医院护理的基本要素，但目前还没有相关研究指导氧饱和度的使用目标以及如何使用(低流量或高流量)以改善预后的最佳方法。在实践中，低收入国家的许多儿童尽管得到了建议，但由于成本高而无法获得氧气，或者供应不可预测(钢瓶或为氧气浓缩器供电的电力不稳定)导致供需不匹配。我们将招募4200名2个月至12岁的非洲儿童入院，他们在2个国家(乌干达和尼日尔)的4家医院接受30个月的呼吸窘迫合并低氧水平(定义为血氧饱和度，SaO2水平低于92%)，并对儿童进行28天的跟踪调查。海岸试验将评估管理的两个相关组成部分1/谁也给氧？在非洲，与氧气水平正常的儿童相比，因缺氧而入院的儿童的住院结局更差。对于缺氧(氧饱和度在80%到92%之间)的儿童，9-10%会在医院死亡，同样，如果他们有严重的缺氧(氧饱和度和80%)，也会有26%-30%的死亡。COSTAR将研究氧气是否改善了缺氧的结局，以及在没有严重缺氧(氧饱和度为80%-92%)的儿童中给氧的最佳阈值。严重缺氧的儿童(SaO2和lt；80%)都将接受氧气，因为我们不太确定氧气在这一组中的好处。对于SaO2在80%到92%之间的儿童，我们不确定哪种水平的氧气是最好的，以及这是否会带来更好的结果--所以一半的孩子会得到氧气，另一半孩子不会得到氧气。如何最好地给氧？我们将比较在所有接受氧气的儿童中，是否通过有两个小尖头的管子进入鼻子的低流量(护理标准)和高流量。高流量氧气为呼吸道提供额外的压力，防止它们在每次呼气后坍塌。对于儿童和婴儿来说，高流量是安全的，而且耐受性很好--因为它有助于减少危重儿童的呼吸努力，当肺部充血感染时，这一点会很严重，这往往会导致无法使用机械通风的儿童(非洲的大多数医院)出现呼吸衰竭和最终呼吸衰竭。主要目标(或结果)是将48小时(主要终点)的短期死亡率和长期发病率和死亡率降低到28天。一项证明氧气是一种重要的挽救生命的治疗的试验将提供重要的新证据，说明哪种水平的氧气治疗对临床有益，对卫生服务来说也是划算的。这将导致对治疗建议的实质性改进，并可用来向卫生服务施加压力，要求更广泛地实施--使政策制定者能够就如何最好地分配稀缺的卫生资源做出决定。

The Children's Oxygen Administration Strategies Trial (COAST) is a multicentre randomised controlled trial aimed at identifying which children admitted to hospital with suspected pneumonia with a low level of oxygen in their blood (called hypoxia) would benefit from oxygen and whether oxygen is best delivered by low flow (routine care) or by high flow. Although oxygen is a basic element of hospital care, there are no relevant studies to guide which level of oxygen saturation should be target for its use and what is the best method of how to administer it (low flow or high flow) to improve outcome. In practise many children in low-income countries do not receive oxygen, despite being recommended, owing to the lack of its availability due to the high cost, or supplies that are unpredictable (erratic delivery of cylinders or electricity to power oxygen concentrators) resulting in mismatch between supply and demand.We will enrol 4200 African children, aged 2 months to 12 years, at admission to hospital with respiratory distress complicated by low oxygen levels (defined as a blood oxygen saturation, SaO2 level below 92%) over 30 months in 4 hospital in 2 countries (Uganda and Niger) and follow the children up over a period of 28 days. COAST trial will evaluate two related components of management.1/ Who to give oxygen too? Children who are admitted to hospital in Africa with hypoxia have a poorer in-hospital outcome than children with normal oxygen levels. For children with hypoxia (oxygen saturations between 80% and 92%) between 9-10% will die in hospital, similarly 26-30% will die if they have severe hypoxia (oxygen saturations <80%). COAST will examine whether or not oxygen improves outcome in hypoxia and the best threshold for giving oxygen in children without severe hypoxia (oxygen saturations 80% - 92%). Children with severe hypoxia (SaO2 <80%) will all receive oxygen as we less unsure about the benefits of oxygen in this group. For the children with SaO2 between 80 and 92% we are not certain which is the best level to provide oxygen and whether this will result in a better outcome - so half of the children will receive oxygen the other half will not receive oxygen.2. How best to give oxygen?We will compare whether giving oxygen through a tube with two small prongs into the nose low flow (standard of care) to high flow in all children receiving oxygen. High flow oxygen provides extra pressure to the airways to prevent them from collapsing after every expiratory breath. High flow is safe and well tolerated in children and babies - as it helps reduce effort of breathing in critically sick children, which is substantial when lungs are congested with infection, that often leads to respiratory exhaustion and ultimately respiratory failure in the children who cannot access mechanical ventilation (the majority of hospitals in Africa). The major aim (or outcome) is to reduce shorter-term mortality at 48-hours (primary endpoint) and longer-term morbidity and mortality to 28 days.A trial demonstrating that oxygen is an important life saving treatment will provide important new evidence for which level of oxygen saturation to target oxygen therapy that is both clinically beneficial and cost-effective for health services. This would lead to substantial refinements to treatment recommendations and can be used to put pressure on health services for wider implementation - allowing policymakers to make decisions on how best to allocate scarce health resources.