Epinephrine Dose: Optimal Versus Standard Evaluation Trial

Study Overview
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Brief Summary
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The objective of this randomized controlled trial is to evaluate the effectiveness of a low cumulative dose of epinephrine compared to a standard cumulative dose of epinephrine during resuscitation from ventricular fibrillation (VF) or ventricular tachycardia (VT) in adult out-of-hospital cardiac arrest (OHCA) patients.

Detailed Description
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This study is designed as a prospective, multicentre, single-blinded randomized controlled trial (RCT) where eligible OHCA patients are randomized to receive a low cumulative dose of epinephrine (low dose epinephrine, up to 2mg total) or a standard cumulative dose of epinephrine (standard dose epinephrine, up to 6mg total) in a 1:1 fashion. Eligible OHCA patients will be treated by emergency medical service (EMS) providers who will initiate cardiopulmonary resuscitation (CPR) and the delivery of defibrillation shocks per EMS treatment protocols. After one defibrillation and when feasible, EMS providers will establish peripheral intravenous (IV) access, and patients will be randomly allocated to 1 of the 2 study arms. Subsequent study drug doses will be administered every 3-5 minutes, based on current guidelines and paramedic protocols, during resuscitation until the first return of spontaneous circulation (ROSC) is achieved or if resuscitation has been terminated by the base hospital physician. Other medications (e.g. antiarrhythmics, magnesium, beta blockers) and interventions (e.g. intubation) may be interposed as required. Follow-up will take place using a combination of administrative databases (e.g. the Discharge Abstract Database and the National Ambulatory Care Reporting System) and telephone interviews. This RCT will evaluate a fundamental change in the treatment of OHCA. The investigators hypothesize that a low cumulative dose of epinephrine will improve patient survival to hospital discharge compared to a standard cumulative dose of epinephrine.

Official Title
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CanROC Epinephrine Dose: Optimal Versus Standard Evaluation Trial (CanROC EpiDOSE Trial)

Conditions
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Cardiac Arrest, Out-Of-Hospital, Sudden Cardiac Arrest, Ventricular Fibrillation, Ventricular Tachycardia-Pulseless

Intervention / Treatment
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* Drug: Epinephrine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Out-of-hospital cardiac arrest treated by paramedics Initial recorded cardiac rhythm of VF or pulseless VT, or, AED shock on first analysis administered or witnessed by EMS (paramedic or fire) Established intravenous vascular access Exclusion Criteria: Known or apparent age <18 years Initial recorded cardiac rhythm of pulseless electrical activity or asystole Cardiac arrest due to an obvious non-cardiac primary cause (e.g. blunt or penetrating trauma, exsanguination, burns, drug overdose, drowning, anaphylaxis, sudden asphyxiation, etc.) Prisoners or persons in police custody Known allergy or sensitivity to epinephrine Prior receipt of non-study kit intravenous, intraosseous, or intramuscular epinephrine during resuscitation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Low Dose Epinephrine<br>Epinephrine up to 2mg total | Drug: Epinephrine<br>* Epinephrine 1mg 1:10000 (10cc) per dose<br>* Other names: Adrenaline;|
| Active Comparator: Standard Dose Epinephrine<br>Epinephrine up to 6mg total | Drug: Epinephrine<br>* Epinephrine 1mg 1:10000 (10cc) per dose<br>* Other names: Adrenaline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival to hospital discharge | Individuals discharged alive from hospital | Through study completion (up to 5 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Return of spontaneous circulation in out-of-hospital setting | Return of spontaneous circulation in the field | Through study completion (up to 5 years) | 
| Survival to emergency department arrival | Individuals alive upon arrival to a hospital emergency department | Through study completion (up to 5 years) | 
| Survival to admission with death prior to discharge | Individuals alive upon hospital admission who die in-hospital before being discharged | Through study completion (up to 5 years) | 
| Survival to discharge outside of a long-term healthcare facility e.g. nursing home | Individuals discharged alive from hospital to a care facility | Through study completion (up to 5 years) | 
| Modified Rankin Scale (mRS) score | Assessment of neurological function, scores range from 0 to 6 where higher scores indicate worse neurological function (0=no symptoms, 6=dead) | 12+/-3 months | 
| Health Utility Index-3 (HUI-3) score | Assessment of quality of life, scores range from -0.36 to 1 where higher scores indicate better quality life (negative scores=a state worse than being dead, 0=dead, 1=perfect health) | 12+/-3 months | 
| Hospital Anxiety and Depression Scale score | Assessment of quality of life, scores range from 0 to 21 where higher scores indicate more anxiety/depression | 12+/-3 months | 
| Length of stay in hospital | Length of time an individual remained in-hospital (length in days) | Through study completion (up to 5 years) | 
| Length of stay in critical care unit | Length of time an individual remained in a crucial care unit (length in days) | Through study completion (up to 5 years) | 
| Survival post-arrest | Survival following hospital discharge, up to 5 years | Up to 5 years | 
| Recurrent cardiac arrest(s) | Number of cardiac arrests following the index arrest | Up to 5 years | 
| ICD implant post-arrest | Whether an implantable cardioverter defibrillator was implanted post-arrest | Up to 5 years | 
| Cardiovascular re-hospitalization(s) | Number of cardiovascular re-hospitalizations | Up to 5 years | 
| All-cause re-hospitalizations(s) | Number of re-hospitalizations for any reason | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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out-of-hospital cardiac arrest, sudden cardiac arrest, epinephrine, randomized controlled trial