Background Acute respiratory failure (ARF) is a common and life-threatening medical emergency. Continuous positive airway pressure (CPAP) is a potentially beneficial prehospital treatment, but it is uncertain whether this could improve important outcomes in NHS ambulance services. Methods An individually randomised, external pilot study was conducted to test the feasibility of a definitive pragmatic trial. Adults with respiratory distress and peripheral oxygen saturations below British Thoracic Society target levels were recruited from the West Midlands Ambulance Service between August 2017 and July 2018. Participants were randomised 1:1 to prehospital CPAP or standard oxygen therapy. Feasibility objectives estimated the: incidence of eligible patients; proportion recruited and allocated to treatment appropriately; adherence to allocated treatment; retention and data completeness; and 30-day mortality, as a potential primary outcome for a definitive trial. Results Over 12 months, 77 patients were enrolled (CPAP arm 42, standard oxygen arm 35 cases, target 120). CPAP was fully delivered as planned in 74% (target 75%). There were no major protocol violations/non-compliances (target 0%). Full data were available for key outcomes (target ≥90%). Mortality was higher than expected (overall 27.3%, CPAP arm 28.6% n=12/42, standard care arm 25.7% n=9/35). Of deceased patients, 14/21 (68%) either did not have a respiratory condition or had ceiling of treatment decisions excluding hospital non-invasive ventilation and critical care. Two patients required emergency department treatment for a pneumothorax, neither having received prehospital CPAP. There were no other serious adverse events. Conclusions The lower than expected recruitment rate, limited compliance with CPAP, and the difficulty in identifying patients who could benefit from CPAP, indicate limited potential for prehospital CPAP to reduce mortality. A definitive effectiveness trial is therefore not recommended. These findings also argue against routine implementation of CPAP into NHS ambulance services.

Despite its use since the 1960s, the safety or effectiveness of adrenaline as a treatment for cardiac arrest has never been comprehensively evaluated in a clinical trial. Although most studies have found that adrenaline increases the chance of return of spontaneous circulation for short periods, many studies found harmful effects on the brain and raise concern that adrenaline may reduce overall survival and/or good neurological outcome. The PARAMEDIC-2 trial seeks to determine if adrenaline is safe and effective in out-of-hospital cardiac arrest.This is a pragmatic, individually randomised, double blind, controlled trial with a parallel economic evaluation. Participants will be eligible if they are in cardiac arrest in the out-of-hospital environment and advanced life support is initiated. Exclusions are cardiac arrest as a result of anaphylaxis or life threatening asthma, and patient known or appearing to be under 16 or pregnant.8000 participants treated by 5 UK ambulance services will be randomised between December 2014 and August 2017 to adrenaline (intervention) or placebo (control) through opening pre-randomised drug packs. Clinical outcomes are survival to 30 days (primary outcome), hospital discharge, 3, 6 and 12 months, health related quality of life, and neurological and cognitive outcomes (secondary outcomes).Trial registration (ISRCTN73485024).