Title: Pre-hospitAl Randomised triAl of MEDICation route in out-of-hospital cardiac arrest (PARAMEDIC3)
Funder: Department of Health and Social Care

Abstract: AIMS OF THE RESEARCH_x000D_ _x000D_ To find out if giving drugs through a vein or into the bone is the most effective way to treat someone when their heart suddenly stops working. _x000D_ _x000D_ BACKGROUND_x000D_ _x000D_ Each year over 30,000 people’s hearts suddenly stop beating in communities around the UK (a condition known as cardiac arrest). Within seconds of this happening the person collapses into a coma. Unless the heart is restarted quickly, the brain will become permanently damaged and the person will die. Injecting drugs such as adrenaline through a vein is very effective at restarting the heart. However, for many people drugs are given too late to save them. This partly explains why less than one in ten people survive an out of hospital cardiac arrest._x000D_ _x000D_ Current guidelines advise paramedics to inject drugs in to a vein. The problem with this is it can take several critical minutes to put a drip in to a vein, ready to give drugs. A new, faster way of giving drugs is to put a small needle into an arm or leg bone. This allows drugs to be injected directly into the rich blood supply found in the bone marrow. Some research studies suggest this may be as good, if not better, than injecting drugs into the vein. Other studies suggest it may be less effective. None of the existing research is good enough to help paramedics decide how best to treat people with cardiac arrest. _x000D_ _x000D_ DESIGN AND METHODS USED_x000D_ _x000D_ We plan to test whether injecting drugs into the vein or the bone is most effective. NHS Paramedics will do this by injecting drugs into some people through the vein and others into the bone marrow. The study will look at how good each method is at restarting the heart and whether it makes a difference to how well people recover after cardiac arrest. The study will work out which treatment provides the NHS with the best value for money. _x000D_ _x000D_ PATIENT AND PUBLIC INVOLVEMENT_x000D_ _x000D_ We have worked closely with patients and the public to develop this proposal and will continue to do so. The idea behind the trial was presented to a meeting of patients, the public, doctors and nurses. Our patient and public member of the research team has helped us design and explain the research plan. A group of patients and relatives affected by cardiac arrest helped us decide what was important for us to find out. _x000D_ _x000D_ We will set up a patient and public group at the start of the study. We will meet regularly during the study, to help us keep focused on the needs of patients and the public. We will work together to communicate information about the study. We will support our patient colleagues by providing training and support through the Clinical Research Ambassador Group. Their time and expenses will be paid according to national guidelines. _x000D_ _x000D_ _x000D_ DISSEMINATION_x000D_ _x000D_ We will share information with patients and the public, paramedics and NHS leaders. We will start as soon as the study begins and continue during the study. _x000D_ _x000D_ We will make use of pictures, stories, talks, reports and social media to help people understand about the research. _x000D_ _x000D_ We will tell those who write the NHS national guidelines about the study findings. This will ensure the study findings can have an immediate effect on patient care. _x000D_ _x000D_ We will share information about our patient and public partnership alongside the study findings.

Lay abstract: RESEARCH QUESTION: _x000D_ _x000D_ Population: Adults with out-of-hospital cardiac arrest_x000D_ _x000D_ Intervention: Intraosseous (IO) first strategy_x000D_ _x000D_ Comparator: Current NHS treatment (2 attempts at IV access before attempting IO access)_x000D_ _x000D_ Outcomes: Survival, favourable neurological outcome, health-related quality of life and cost effectiveness_x000D_ _x000D_ Study design: Multi-centre, pragmatic, individually randomised, parallel group, trial and economic evaluation_x000D_ _x000D_ Timeline: 48 months._x000D_ _x000D_ BACKGROUND: 30,000 people sustain an out-of-hospital cardiac arrest each year. Parenteral drugs are an effective treatment and the earlier drugs are given the greater their impact. The best route for administering drugs is currently unknown, resulting in variation in practice and uncertainty about the optimal approach._x000D_ _x000D_ AIM: To conduct a multi-centre, pragmatic, individually randomised, parallel group, superiority trial and economic evaluation to determine the clinical and cost effectiveness of an intraosseous access first strategy, versus current NHS treatment. The trial will include an internal pilot to confirm feasibility. _x000D_ _x000D_ OBJECTIVES: _x000D_ _x000D_ (1) Conduct an internal pilot study to confirm the feasibility of the large-scale multicentre trial _x000D_ _x000D_ (2) Determine the clinical effectiveness of an IO first strategy for adults with out-of-hospital cardiac arrest upon survival, favourable neurological outcomes and health-related quality of life._x000D_ _x000D_ (3) Estimate, in an integrated economic evaluation, the cost-effectiveness of an IO first strategy._x000D_ _x000D_ METHODS:_x000D_ _x000D_ Setting: NHS Ambulance Services across England and Wales._x000D_ _x000D_ Randomisation: Allocation concealed, randomisation (1:1), stratified by ambulance service. _x000D_ _x000D_ Inclusion criteria:_x000D_ _x000D_ • Adult (age >18)_x000D_ • Out-of-hospital cardiac arrest_x000D_ • Requirement for vascular access to administer cardiac arrest drugs _x000D_ _x000D_ Exclusion criteria: _x000D_ _x000D_ • Known or suspected pregnancy_x000D_ • Already have vascular access_x000D_ _x000D_ _x000D_ Health technologies being assessed: Intraosseous first strategy compared with current NHS treatment (2 attempts at IV access before IO access)_x000D_ _x000D_ Primary outcome: _x000D_ _x000D_ • Survival to 30 days_x000D_ _x000D_ Secondary outcomes:_x000D_ _x000D_ • Any return of spontaneous circulation (ROSC)_x000D_ • Time to ROSC_x000D_ • Survived event (sustained ROSC at hospital handover) _x000D_ • Survival to hospital discharge, 3 and 6 months_x000D_ • Neurological outcome (modified Rankin Scale) at discharge, 3, and 6 months_x000D_ • Health related quality of life (EQ-5D-5L) at 3 and 6 months _x000D_ • Hospital and intensive care length of stay_x000D_ _x000D_ Economic outcomes: _x000D_ _x000D_ • Incremental cost per quality-adjusted life year gained from the perspective of the NHS and personal social services. _x000D_ • Within-trial and life-time model estimates will be generated._x000D_ _x000D_ Sample size: 15,000 participants (90% power, 5% significance, to detect 1% absolute difference in survival)._x000D_ _x000D_ ANTICIPATED IMPACT AND DISSEMINATION: _x000D_ _x000D_ The study will provide definitive evidence for the most effective vascular access strategy during out-of-hospital cardiac arrest. The findings will define future NHS and international practice. A 1% absolute difference in survival will translate to an additional 150 lives saved each year in the NHS. _x000D_ _x000D_ We will publish lay and professional summaries in written, audible and infographic styles. We will disseminate through public engagement events, peer reviewed publications, podcasts, blogs, conference presentations social media and our membership of key organisations

Research activity codes: 6.3 MEDICAL DEVICES
Health categories: CARDIOVASCULAR