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

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.

PMID: 38260121
PMCID: PMC10801302
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)

Keith Couper et al. Resusc Plus. 2023.

. 2023 Dec 30:17:100544.

doi: 10.1016/j.resplu.2023.100544. eCollection 2024 Mar.

Authors

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.

PMID: 38260121
PMCID: PMC10801302
DOI: 10.1016/j.resplu.2023.100544

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.

PubMed Disclaimer

Conflict of interest statement

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: GDP is co-chair of the International Liaison Committee on Resuscitation (ILCOR). CD and JPN are emeritus members of the ILCOR Advanced Life Support task force. KC and HP are current members of the ILCOR Advanced Life Support task force. GDP is editor-in-chief and JPN is founding editor of Resuscitation Plus. KC is associate editor of Resuscitation Plus and guest editor for the research methodology special edition.

Figures

**Fig. 1**
**PARAMEDIC-3 trial CONOSRT diagram.** Figure footer: OHCA- out-of-hospital cardiac arrest; IO- Intraosseous; IV- Intravenous.

See this image and copyright information in PMC

References

1. Hawkes C., Booth S., Ji C., et al. Epidemiology and outcomes from out-of-hospital cardiac arrests in England. Resuscitation. 2017;110:133–140. - PubMed
1. Perkins G.D., Ji C., Deakin C.D., et al. A randomized trial of epinephrine in out-of-hospital cardiac arrest. New England Journal of Medicine. 2018;379:711–721. - PubMed
1. Perkins G.D., Kenna C., Ji C., et al. The influence of time to adrenaline administration in the Paramedic 2 randomised controlled trial. Intensive Care Med. 2020;46:426–436. - PMC - PubMed
1. Reades R., Studnek J.R., Garrett J.S., et al. Comparison of first-attempt success between tibial and humeral intraosseous insertions during out-of-hospital cardiac arrest. Prehosp Emerg Care. 2011;15:278–281. - PubMed
1. Ross E.M., Mapp J., Kharod C., et al. Time to epinephrine in out-of-hospital cardiac arrest: a retrospective analysis of intraosseous versus intravenous access. Am J Disaster Med. 2016;11:119–123. - PubMed

LinkOut - more resources

Full Text Sources

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

Full Text Sources