MICA: Children's Oxygen Administration Strategies Trial

儿童氧气管理策略试验（COAST）是一项多中心随机对照试验，旨在确定哪些因血液中含氧量低（称为缺氧）的疑似肺炎住院的儿童将受益于氧气，以及氧气最好通过低流量（常规护理）或高流量输送。虽然氧气是医院护理的基本要素，但没有相关研究来指导其使用的目标氧饱和度水平以及如何管理它（低流量或高流量）以改善结果的最佳方法。实际上，低收入国家的许多儿童得不到氧气，尽管有人建议，原因是氧气费用高，供应不可预测（氧气瓶或氧气浓缩器供电的电力输送不稳定）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，在2个国家（乌干达和尼日尔）的4家医院，在入院时患有呼吸窘迫并发低氧水平（定义为血氧饱和度，SaO 2水平低于92%）超过30个月，并在28天内对儿童进行随访。COAST试验将评估两个相关的管理组成部分。1/谁也给氧？在非洲，因缺氧而入院的儿童比氧气水平正常的儿童的住院结果更差。对于缺氧（氧饱和度在80%至92%之间）的儿童，9-10%将在医院死亡，同样，如果他们有严重的缺氧（氧饱和度<80%），26-30%将死亡。COAST将检查氧气是否改善缺氧的结果，以及在没有严重缺氧的儿童中给予氧气的最佳阈值（氧饱和度80% - 92%）。重度缺氧（SaO 2 <80%）的儿童都将接受氧气，因为我们不太确定氧气在这一组中的益处。对于SaO 2在80 - 92%之间的儿童，我们不确定提供氧气的最佳水平以及这是否会导致更好的结果-因此一半的儿童将获得氧气，另一半将不获得氧气。如何更好地提供氧气？我们将比较是否给予氧气通过管与两个小叉到鼻子低流量（护理标准），以高流量在所有儿童接受氧气。高流量氧气为气道提供额外的压力，以防止它们在每次呼气后塌陷。高流量对儿童和婴儿是安全的，耐受性良好，因为它有助于减少重症儿童的呼吸努力，当肺部因感染而充血时，这是相当大的，这通常会导致呼吸衰竭，最终导致无法获得机械通气的儿童呼吸衰竭（非洲大多数医院）。其主要目的（或结局）是降低48小时内的短期死亡率（主要终点）和28天内的长期发病率和死亡率。一项证明氧气是一种重要的救生治疗的试验将为氧气治疗的目标氧饱和度水平提供重要的新证据，这对医疗服务既有临床益处又具有成本效益。这将导致对治疗建议的实质性改进，并可用于对卫生服务施加压力，以更广泛地实施-使决策者能够就如何最好地分配稀缺的卫生资源作出决定。

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.