POHCA Resuscitation: Evaluation of IM Epinephrine (PRIME)

Pediatric Out-of-Hospital Cardiac Arrest Resuscitation: Evaluation of IM Epinephrine (The PRIME Trial)

This is a pragmatic, two-arm, open-label, prospective stepped-wedge cluster randomized control trial (SW-CRCT) looking to evaluate early intramuscular (IM) epinephrine in the management of pediatric out-of-hospital cardiac arrest (POHCA).

Study Overview

• Status: Recruiting
• Conditions: Pediatric Out-of-Hospital Cardiac Arrest
• Intervention / Treatment: Drug: Epinephrine Injection

Detailed Description

IM epinephrine may provide a more efficient means of administering the initial epinephrine dose (versus IV/IO administration) to a child experiencing pediatric out of hospital cardiac arrest (POHCA) with no greater risk of harm. In so doing, this may improve the short- and long-term outcomes of these patients. There is an abundance of literature detailing the risk/benefit profile of IM epinephrine use in anaphylaxis; however, there is no human data on this topic as it relates to cardiac arrest. Important knowledge gaps include whether the use of IM epinephrine via autoinjector and/or pre-filled syringe leads to faster administration of the initial doses of epinephrine without delaying time to definitive epinephrine (via IV/IO) and the impact on time to initial and sustained return of spontaneous circulation (ROSC). This trial will be the first to examine the role of IM epinephrine via autoinjector/pre-filled syringe in POHCA.

• Study Type: Interventional
• Enrollment (Estimated): 284
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Maysaa Assaf; Phone Number: 75548 519-685-8500; Email: maysaa.assaf@lhsc.on.ca

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Recruiting
      • Children's Hospital - London Health Sciences Centre
      • Principal Investigator: Janice Tijssen, MD MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Children aged 1 day to and including 17 years experiencing an out-of-hospital cardiac arrest (OHCA)
• Must be receiving at least 1 minute of CPR by trained first responders (police, fire, or paramedic services)

Exclusion Criteria:

- Children who experience OHCA due to an obvious traumatic event.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard of Care; All POHCA events will be handled per standard of care of epinephrine administration via intravenous or intraosseous (IV/IO) based on patient estimated weight.
Other: Intramuscular Epinephrine Dose; POHCA events will be handled per standard of care, however, first dose epinephrine administration will be via intramuscular (IM) autoinjector and/or pre-filled syringes. Dosing will be dependent on weight as follows: 3-<5kg=0.3mg IM epinephrine; 5-<10kg=0.5mg IM epinephrine; 10-<20kg=1.0mg IM epinephrine; 20-<30kg=2.0mg IM epinephrine; 30kg=3.0mg IM epinephrine	Drug: Epinephrine Injection; Epinephrine administered via sterile epinephrine injection USP, by 0.3mg or 0.5mg epinephrine auto-injector(s) and/or pre-filled syringe (exact dose).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to initial return of spontaneous circulation (ROSC)	The primary outcome will be the time to initial ROSC. The investigator will compare time to initial ROSC between the standard of care and intervention periods.	At time of event

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Return of spontaneous circulation	Whether return of spontaneous circulation is achieved or not	At time of event
Time to sustained ROSC	Time to sustained ROSC will be calculated from the time that paramedics arrive on scene to the time that sustained ROSC, defined as chest compressions not required for 20 minutes with persistent signs of circulation, is achieved.	At time of event
Survival	Survival to emergency department transfer to pediatric critical care unit (PCCU), if applicable: admitted to PCCU from external ED	From time of event to ED admission
Survival - comparison between both arms	Survival to hospital admission will be compared between standard of care and intervention periods	From time of event to hospital admission
PCCU/Hospital length of stay	PCCU and hospital length of stay will be calculated from time of admission to the PCCU/hospital and time to discharge from PCCU/hospital, if applicable, between standard of care and intervention periods	From time of hospital/PCCU admission to discharge, up to 1 year
Survival to hospital discharge	Survival to hospital discharge will be compared between standard of care and intervention periods	Dependent on course of hospital stay, up to 1 year
Post POHCA survival	Survival at 6 months and 12 months post-POHCA will be compared between standard of care and intervention periods	Dependent on survival at 6 and 12 month period post POHCA event
Neurological status	The investigator will compare PCPC scores at discharge, 6- and 12-months post-POHCA between the standard of care and intervention periods	From time of discharge and 6 and 12 months post POHCA event
Life Impact and Pediatric Quality of Life assessments	Life Impact assessment between 6 and 12 months: the investigator will use the Pediatric Quality of Life (PEDSQoL, Pediatrics Quality of Life) assessment tool at 6- and 12-months post-POHCA in all survivors and compare between standard of care and intervention periods. The score ranges from 0-100, with higher scores indicating better outcome.	6 and 12 months post POHCA event
Life Impact and Pediatric Quality of Life assessments	Life Impact assessment between 6 and 12 months: the investigator will use the Daily Activities Scale at 6- and 12-months post-POHCA in all survivors and compare between standard of care and intervention periods. This scale is a subscore of the PEDSQoL tool with scores ranging from 0-100, with higher scores indicating better outcome.	6 and 12 months post POHCA event

Collaborators and Investigators

• Sponsor: Lawson Health Research Institute
• Investigators: Principal Investigator: Janice Tijssen, MD MSc, Lawson Health Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: November 22, 2021
• First Submitted That Met QC Criteria: December 8, 2021
• First Posted (Actual): December 21, 2021

Study Record Updates

• Last Update Posted (Estimated): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 23, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: pediatric; cardiac arrest; resuscitation; standard of care; IM Epinephrine
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Arrest; Out-of-Hospital Cardiac Arrest; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-Agonists; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Epinephrine
• Other Study ID Numbers: PRIME-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No