title: Pre-hospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug administration In Cardiac arrest (PARAMEDIC-2): Trial protocol.
abstract: 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).
authors.affiliation: Warwick Clinical Trials Unit, University of Warwick, Coventry CV4 7AL, UK; Heart of England NHS Foundation Trust, Bordesley Green East, Birmingham B9 5SS, UK. Electronic address: g.d.perkins@warwick.ac.uk.
authors.forename: Gavin D
authors.initials: GD
authors.lastname: Perkins
authors.affiliation: Faculty of Health, Social Care and Education, Kingston University London and St. George's, University of London, London SW17 0RE, UK.
authors.forename: Tom
authors.initials: T
authors.lastname: Quinn
authors.affiliation: Respiratory BRU, University Hospital Southampton SO16 6YD, UK; South Central Ambulance Service NHS Foundation Trust, Otterbourne, UK.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Deakin
authors.affiliation: School of Clinical Sciences, University of Bristol, Bristol BS8 1TH, UK; Department of Anaesthesia and Intensive Care Medicine, Royal United Hospital, Bath BA1 3NG, UK.
authors.forename: Jerry P
authors.initials: JP
authors.lastname: Nolan
authors.affiliation: Warwick Clinical Trials Unit, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Ranjit
authors.initials: R
authors.lastname: Lall
authors.affiliation: Warwick Clinical Trials Unit, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Slowther
authors.affiliation: Warwick Clinical Trials Unit, University of Warwick, Coventry CV4 7AL, UK; Heart of England NHS Foundation Trust, Bordesley Green East, Birmingham B9 5SS, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Cooke
authors.affiliation: Kadoorie Centre for Critical Care Research and Education, John Radcliffe Hospital, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 9DU, UK.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Lamb
authors.affiliation: Warwick Clinical Trials Unit, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Stavros
authors.initials: S
authors.lastname: Petrou
authors.affiliation: Warwick Clinical Trials Unit, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Felix
authors.initials: F
authors.lastname: Achana
authors.affiliation: Department of Epidemiology and Preventive Medicine, School of Public Health & Preventive Medicine, Monash University, Melbourne, Australia; Prehospital, Resuscitation and Emergency Care Research Unit (PRECRU), School of Nursing, Midwifery and Paramedicine, Curtin University, Perth, Australia; St John Ambulance Western Australia, Belmont, Australia.
authors.forename: Judith
authors.initials: J
authors.lastname: Finn
authors.affiliation: Department of Epidemiology and Preventive Medicine, School of Public Health & Preventive Medicine, Monash University, Melbourne, Australia; Prehospital, Resuscitation and Emergency Care Research Unit (PRECRU), School of Nursing, Midwifery and Paramedicine, Curtin University, Perth, Australia; St John Ambulance Western Australia, Belmont, Australia.
authors.forename: Ian G
authors.initials: IG
authors.lastname: Jacobs
authors.affiliation: West Midlands Ambulance Service NHS Foundation Trust, Brierley Hill DY5 1LX, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Carson
authors.affiliation: Warwick Clinical Trials Unit, University of Warwick, Coventry CV4 7AL, UK; West Midlands Ambulance Service NHS Foundation Trust, Brierley Hill DY5 1LX, UK.
authors.forename: Mike
authors.initials: M
authors.lastname: Smyth
authors.affiliation: North East Ambulance Service NHS Foundation Trust, Newcastle upon Tyne NE15 8NY, UK.
authors.forename: Kyee
authors.initials: K
authors.lastname: Han
authors.affiliation: North East Ambulance Service NHS Foundation Trust, Newcastle upon Tyne NE15 8NY, UK.
authors.forename: Sonia
authors.initials: S
authors.lastname: Byers
authors.affiliation: Welsh Ambulance Services NHS Trust, Denbighshire, Wales LL17 0RS, UK.
authors.forename: Nigel
authors.initials: N
authors.lastname: Rees
authors.affiliation: Welsh Ambulance Services NHS Trust, Denbighshire, Wales LL17 0RS, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Whitfield
authors.affiliation: London Ambulance Service NHS Trust, 8-20 Pocock Street, London SE1 0BW, UK.
authors.forename: Fionna
authors.initials: F
authors.lastname: Moore
authors.affiliation: Warwick Clinical Trials Unit, University of Warwick, Coventry CV4 7AL, UK; London Ambulance Service NHS Trust, 8-20 Pocock Street, London SE1 0BW, UK.
authors.forename: Rachael
authors.initials: R
authors.lastname: Fothergill
authors.affiliation: Statistics and Epidemiology, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK.
authors.forename: Nigel
authors.initials: N
authors.lastname: Stallard
authors.affiliation: Warwick Clinical Trials Unit, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: John
authors.initials: J
authors.lastname: Long
authors.affiliation: Warwick Clinical Trials Unit, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Susie
authors.initials: S
authors.lastname: Hennings
authors.affiliation: Warwick Clinical Trials Unit, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Jessica
authors.initials: J
authors.lastname: Horton
authors.affiliation: Warwick Clinical Trials Unit, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Kaye
authors.affiliation: Warwick Clinical Trials Unit, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Gates
mesh_terms: D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D002985:Clinical Protocols; D004311:Double-Blind Method; D004632:Emergency Medical Services / Q000706:statistics & numerical data*; D004634:Emergency Medical Technicians; D004837:Epinephrine / Q000627:therapeutic use*; D006801:Humans; D058687:Out-of-Hospital Cardiac Arrest / Q000188:drug therapy* / Q000191:economics / Q000401:mortality; D010865:Pilot Projects; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D017741:Survivors / Q000706:statistics & numerical data; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*
chemical_list: D014662:Vasoconstrictor Agents; D004837:Epinephrine
keywords: Adrenaline; Cardiac arrest; Randomised controlled trial; Vasopressor