High Flow humidified oxygen as an early intervention in children with Acute Severe Asthma: a randomised controlled trial.Short Title: High flow humidified Oxygen in Paediatric acute Severe Asthma (HOPSA)

Research Question and Background: Acute severe asthma (ASA) accounts for 7% of all children attending paediatric emergency departments: of these, 20% fail to respond to first line therapy with high dose inhaled bronchodilators. Usual care for these children is variable, guidelines are imprecise, and evidence is scarce. Most will be treated with intravenous bronchodilators, involving painful cannula insertion and unpleasant side effects. High flow humidified oxygen therapy (HiFlo) involves delivering a warmed, humidified oxygen/air blend, via nasal cannulae at a high flow rate. It has shown promising results in other acute respiratory conditions in children, and in observational studies in ASA. Two small single-centre pilot RCTs of HiFlo in ASA have shown conflicting results. Despite lack of evidence, its use has been rapidly increasing, and a recent review concluded that a large well-designed RCT assessing the efficacy of HiFlo in ASA was urgently needed. Our recent successful feasibility trial has demonstrated that it is possible to undertake an RCT to address the question: In children aged 2-17 years with ASA not responding to high dose inhaled bronchodilator therapy (participants), does early HiFlo (intervention) compared to usual care (comparator) reduce the need for intravenous bronchodilator therapy (outcome)? Aims and Objectives: Aim: to determine whether early HiFlo is an effective intervention in childhood ASA which has not responded to first-line therapy (high dose inhaled bronchodilators). Primary objective: to determine whether in these children, early HiFlo (commenced within 4 hours of starting first-line therapy) reduces need for escalation to intravenous bronchodilator therapy. Secondary objectives: to assess whether HiFlo produces more rapid clinical and subjective improvement, reduces adverse effects, shortens length of stay and reduces costs of treatment. Methods: Design: multicentre randomised controlled trial with deferred consent, of early HiFlo vs usual care. 258 children will be randomised 1:1 across 9 sites to achieve 218 with deferred consent. Eligibility: aged 2 to 17 years, presenting to hospital with ASA requiring high dose "burst" inhaled bronchodilator therapy but failing to respond adequately (persisting hypoxaemia with moderate or severe respiratory distress). Exclusions: signs of pneumonia or contraindications to HiFlo. Primary outcome measure: escalation to intravenous bronchodilator therapy. Key secondary outcomes: rate of clinical improvement (Paediatric Early Warning Score, Asthma Severity Score and respiratory rate at 2 hours, subjective recovery score at 24 hours), incidence of adverse effects, time to discharge and health economic indicators. Design is based on results and experience from our preceding feasibility study, together with workshops with our PPI groups. We have recruited a lived experience panel who will continue to guide us during trial setup, delivery and dissemination. Timelines for delivery: M1-10: trial set up M7-30: recruitment, follow up M31-36: analysis, dissemination Impact and Dissemination: Our results will improve the outcomes and experience of children treated for ASA, bring greater clarity to guidelines for healthcare professionals, and ensure cost-effective management of ASA in the NHS. We will disseminate our findings in partnership with our PPI groups and healthcare professionals, including previously well-established clinical research networks via conferences, publications, and NHS guidelines.