Title: The ACUTE (Ambulance CPAP: Use, Treatment effect and Economics) feasibility study: A pilot randomised controlled trial of prehospital CPAP for acute respiratory failure
Funder: Department of Health and Social Care

Abstract: AIM: To determine whether it is feasible, acceptable and cost-effective to undertake a definitive pragmatic randomised controlled trial comparing prehospital CPAP to standard oxygen therapy in patients presenting with acute respiratory failure DESIGN: a) Individual patient randomised controlled pilot trial b) Updated value of information analysis of existing HTA economic model SETTING: Four ambulance hubs in the West Midlands Ambulance Service PARTICIPANTS: Adults presenting to paramedics with acute respiratory failure and recruited according to the 2005 Mental Capacity Act SAMPLE SIZE: A sample size of 1,508 is projected for the full trial (based on 5% absolute effect size, 88% baseline 30 day survival, 90% power, 2-sided significance of 5%, 5% attrition at 30 days). Recruitment of at least 120 participants to the pilot trial over 12 months will demonstrate that a definitive trial is feasible and cost-effective. It will also allow estimation of adherence, attrition, data completeness and event rates with sufficient precision to ensure validity of the definitive trial protocol. INCLUSION CRITERIA: Respiratory distress with peripheral oxygen saturation below BTS target levels (88% for patients with COPD, 94% for other conditions), despite supplemental oxygen EXCLUSION CRITERIA: Hospital treatment available within 15 minutes of eligibility, trauma aetiology, terminal illness, not for resuscitation status, suspected pneumothorax, anticipated inability to apply CPAP, oxygen alert card, need for immediate intubation, age <18 years, epistaxis, vomiting HEALTH TECHNOLOGIES ASSESSED: Prehospital CPAP (O_two system) with supplemental oxygen versus standard oxygen therapy; both titrated to BTS recommendations for peripheral oxygen saturations. Interventions provided in identical sealed boxes to ensure allocation concealment FEASIBILITY OUTCOMES: 1. Incidence of recruited eligible patients; 2. Recruitment of patients meeting eligibility criteria; 3. Adherence to the allocation schedule (i.e. initiation of allocated treatment); 4. Adherence to treatment (i.e. crossovers recorded prior to hospital arrival); 5. Attrition at 30 days; 6. Feasibility of data collection, based on proportion with missing or incomplete data; 7. Cost-effectiveness of definitive trial using value of information analysis of updated economic model EFFECTIVENESS OUTCOMES: Survival at 30 days (definitive trial primary endpoint); endotracheal intubation; admission to critical care; length of hospital stay; EQ-5D-3L and health-care resource use at 30 days ACCEPTABILITY OUTCOMES: Adverse events and side effects. Paramedic perceptions about, and satisfaction with, each intervention DATA COLLECTION: Efficient collection of baseline, outcome and adverse event data using ambulance service electronic patient report forms, emergency department information systems, and NHS Summary Care Records. Quality of life and resource use postal questionnaires. Assessment of paramedic acceptability using online survey. ANALYSIS: Feasibility outcomes will be analysed descriptively (point estimates reported with 95% confidence intervals) and compared to pre-specified target values. Effectiveness outcomes will be reported descriptively. The existing meta-analysis and economic model will be updated and an expected net benefit of sampling analysis undertaken. TIMETABLE: 28m project: 8m set-up; 1m training for paramedics; 12m recruitment; 1m follow-up; 6m close out, analysis and write-up

Lay abstract: BACKGROUND Acute respiratory failure is a common and life-threatening medical emergency that often results in prolonged hospital stays or expensive intensive care admissions. It occurs when heart or lung disease suddenly develops or worsens and leads to the patient being unable to maintain oxygen levels in their blood. When this happens the patient is at high risk of death and needs emergency treatment. Paramedics currently provide oxygen delivered at normal pressure by a loose fitting face mask. Continuous positive airway pressure (CPAP) is a potentially useful treatment that could be delivered by paramedics in an ambulance. It involves delivering oxygen under increased pressure through a tight-fitting facemask. Its use in hospital can reduce the risk of death in people with lung disease and improve breathing in people with heart disease. Small studies undertaken outside the UK have suggested that using CPAP in an ambulance may save more lives than delaying its use until arrival at hospital. However, it is uncertain whether this treatment could work effectively in NHS ambulance services, and if it represents value for money. AIM The purpose of this study is to see whether it is possible and worthwhile to undertake a full-scale study comparing CPAP and standard oxygen treatment for acute respiratory failure, and if so, how we should do it. METHODS Paramedics will identify adults with acute respiratory failure when attending 999 emergency calls. We aim to include 120 patients in the study. Half will be randomly assigned to a group that will receive CPAP, while the other half will be treated with standard oxygen therapy. All the patients will then undergo normal hospital treatment and be followed up for a month to see if they survive. We will also measure each patient’s quality of life, need for admission to intensive care, and length of stay in hospital. Additionally, we will look at how many adults are attended with acute respiratory failure and are entered into study, the number who correctly receive CPAP treatment, and how many patients we can follow up to the end of the study. Paramedics will also be surveyed to understand their experience of delivering CPAP and aspects of the research. Together these results will tell us whether it is feasible and affordable to conduct a full -scale study evaluating CPAP for acute respiratory failure, and will inform us how to design it. The main ethical issue is that the trial will involve patients who are severely ill and unable to decide whether they wish to participate. In these circumstances patients can be recruited to the trial and their consent sought later, provided important legal safeguards are adhered to. We have consulted with representatives from relevant patient groups to ensure that this process respects the patient's dignity and autonomy. EXPERTISE Our research team has extensive experience of undertaking trials of emergency treatments and is familiar with the complex ethical and legal issues when undertaking these studies. People who have experienced medical emergencies and breathing problems have been consulted in the development of this project. We will continue to involve patient and public representatives to ensure that the needs of potentially vulnerable patients are taken into account throughout the study

Research activity codes: 6.7 PHYSICAL
Health categories: RESPIRATORY