POHCA Resuscitation: Evaluation of IM Epinephrine

Study Overview
=================
Brief Summary
-----------------
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).

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 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 in POHCA.

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

Conditions
-----------------
Pediatric Out-of-Hospital Cardiac Arrest

Intervention / Treatment
-----------------
* Drug: Epinephrine Injection


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 1 Day
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Paramedic services across Ontario will participate in the study. All sites will begin with a period of baseline data collection (standard of care arm) and will cross over to the intervention arm (Intramuscular Epinephrine Dose arm) on a staggered schedule and in random order. Each site will remain in the intervention arm, once cross over happens, for the duration of the study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard of Care<br>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<br>POHCA events will be handled per standard of care, however, first dose epinephrine administration will be via intramuscular (IM) autoinjector. Dosing will be dependent on weight as follows: 3-<5kg=0.3mg IM epinephrine 5-<10kg=0.5mg IM epinephrine 10-<25kg=1.0mg IM epinephrine 25kg=1.5mg IM epinephrine | Drug: Epinephrine Injection<br>* Epinephrine administered via sterile epinephrine injection USP, by 0.3mg or 0.5mg epinephrine auto-injector(s)<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cardiac arrest, IM Epinephrine, standard of care, pediatric, resuscitation