Route of drug administration in out-of-hospital cardiac arrest: A protocol for a randomised controlled trial (PARAMEDIC-3)

Keith Couper; Chen Ji; Ranjit Lall; Charles D Deakin; Rachael Fothergill; John Long; James Mason; Felix Michelet; Jerry P Nolan; Henry Nwankwo; Tom Quinn; Anne-Marie Slowther; Michael A Smyth; Alison Walker; Loraine Chowdhury; Chloe Norman; Laurille Sprauve; Kath Starr; Sara Wood; Steve Bell; Gemma Bradley; Martina Brown; Shona Brown; Karl Charlton; Alison Coppola; Charlotte Evans; Christine Evans; Theresa Foster; Michelle Jackson; Justin Kearney; Nigel Lang; Adam Mellett-Smith; Ria Osborne; Helen Pocock; Nigel Rees; Robert Spaight; Belinda Tibbetts; Gregory A Whitley; Jason Wiles; Julia Williams; Adam Wright; Gavin D Perkins

doi:10.1016/j.resplu.2023.100544

Route of drug administration in out-of-hospital cardiac arrest: A protocol for a randomised controlled trial (PARAMEDIC-3)

Resusc Plus. 2023 Dec 30:17:100544. doi: 10.1016/j.resplu.2023.100544. eCollection 2024 Mar.

Authors

Keith Couper^{1

2}, Chen Ji¹, Ranjit Lall¹, Charles D Deakin^{3

4}, Rachael Fothergill^{1

5}, John Long¹, James Mason¹, Felix Michelet¹, Jerry P Nolan^{1

6}, Henry Nwankwo¹, Tom Quinn⁷, Anne-Marie Slowther⁸, Michael A Smyth¹, Alison Walker^{9

10}, Loraine Chowdhury¹, Chloe Norman¹, Laurille Sprauve¹, Kath Starr¹, Sara Wood¹, Steve Bell¹¹, Gemma Bradley¹², Martina Brown⁴, Shona Brown¹³, Karl Charlton¹⁴, Alison Coppola¹⁵, Charlotte Evans¹⁶, Christine Evans⁹, Theresa Foster¹³, Michelle Jackson¹⁴, Justin Kearney⁵, Nigel Lang¹⁷, Adam Mellett-Smith^{1

5}, Ria Osborne¹⁵, Helen Pocock^{1

4}, Nigel Rees¹⁶, Robert Spaight¹⁸, Belinda Tibbetts¹⁷, Gregory A Whitley¹⁸, Jason Wiles⁹, Julia Williams^{12

19}, Adam Wright¹¹, Gavin D Perkins^{1

2}

Affiliations

¹ Warwick Clinical Trials, University of Warwick, Coventry, UK.
² Critical Care Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
³ University Hospital Southampton NHS Foundation Trust, Southampton, UK.
⁴ South Central Ambulance NHS Foundation Trust, Otterbourne, UK.
⁵ Clinical Audit and Research Unit, London Ambulance Service, London, UK.
⁶ Department of Anaesthesia, Royal United Hospitals Bath NHS Foundation Trust, Bath, UK.
⁷ Kingston University, London, UK.
⁸ Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry, UK.
⁹ West Midlands Ambulance Service University NHS Foundation Trust, Brierly Hill, UK.
¹⁰ Emergency Department, Harrogate and District NHS Foundation Trust, Harrogate, UK.
¹¹ North West Ambulance Service NHS Trust, Bolton, UK.
¹² Research and Development Department, South East Coast Ambulance Service NHS Foundation Trust, Crawley, UK.
¹³ East of England Ambulance Service NHS Trust, Melbourn, UK.
¹⁴ North East Ambulance Service NHS Foundation Trust, Newcastle upon Tyne, UK.
¹⁵ South Western Ambulance Service NHS Foundation Trust, Exeter, UK.
¹⁶ Welsh Ambulance Services NHS Trust, Cwmbran, UK.
¹⁷ Devon Air Ambulance Trust, Exeter, UK.
¹⁸ East Midlands Ambulance Service NHS Trust, Nottingham, UK.
¹⁹ Department of Paramedic Science, University of Hertfordshire, Hatfield, UK.

Abstract

Aims: The PARAMEDIC-3 trial evaluates the clinical and cost-effectiveness of an intraosseous first strategy, compared with an intravenous first strategy, for drug administration in adults who have sustained an out-of-hospital cardiac arrest.

Methods: PARAMEDIC-3 is a pragmatic, allocation concealed, open-label, multi-centre, superiority randomised controlled trial. It will recruit 15,000 patients across English and Welsh ambulance services. Adults who have sustained an out-of-hospital cardiac arrest are individually randomised to an intraosseous access first strategy or intravenous access first strategy in a 1:1 ratio through an opaque, sealed envelope system. The randomised allocation determines the route used for the first two attempts at vascular access. Participants are initially enrolled under a deferred consent model.The primary clinical-effectiveness outcome is survival at 30-days. Secondary outcomes include return of spontaneous circulation, neurological functional outcome, and health-related quality of life. Participants are followed-up to six-months following cardiac arrest. The primary health economic outcome is incremental cost per quality-adjusted life year gained.

Conclusion: The PARAMEDIC-3 trial will provide key information on the clinical and cost-effectiveness of drug route in out-of-hospital cardiac arrest.Trial registration: ISRCTN14223494, registered 16/08/2021, prospectively registered.

Keywords: Cardiac arrest; Clinical trial protocol; Epinephrine; Intraosseous; Intravenous.