EpiDOSE: Epinephrine Dose: Optimal Versus Standard Evaluation Trial
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Low Dose Epinephrine Epinephrine up to 2mg total |
Drug: Epinephrine
Epinephrine 1mg 1:10000 (10cc) per dose
Other Names:
|
| Active Comparator: Standard Dose Epinephrine Epinephrine up to 6mg total |
Drug: Epinephrine
Epinephrine 1mg 1:10000 (10cc) per dose
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Survival to hospital discharge [Through study completion (up to 5 years)]
Individuals discharged alive from hospital
Secondary Outcome Measures
- Return of spontaneous circulation in out-of-hospital setting [Through study completion (up to 5 years)]
Return of spontaneous circulation in the field
- Survival to emergency department arrival [Through study completion (up to 5 years)]
Individuals alive upon arrival to a hospital emergency department
- Survival to admission with death prior to discharge [Through study completion (up to 5 years)]
Individuals alive upon hospital admission who die in-hospital before being discharged
- Survival to discharge outside of a long-term healthcare facility e.g. nursing home [Through study completion (up to 5 years)]
Individuals discharged alive from hospital to a care facility
- Modified Rankin Scale (mRS) score [12+/-3 months]
Assessment of neurological function, scores range from 0 to 6 where higher scores indicate worse neurological function (0=no symptoms, 6=dead)
- Health Utility Index-3 (HUI-3) score [12+/-3 months]
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)
- Hospital Anxiety and Depression Scale score [12+/-3 months]
Assessment of quality of life, scores range from 0 to 21 where higher scores indicate more anxiety/depression
- Length of stay in hospital [Through study completion (up to 5 years)]
Length of time an individual remained in-hospital (length in days)
- Length of stay in critical care unit [Through study completion (up to 5 years)]
Length of time an individual remained in a crucial care unit (length in days)
- Survival post-arrest [Up to 5 years]
Survival following hospital discharge, up to 5 years
- Recurrent cardiac arrest(s) [Up to 5 years]
Number of cardiac arrests following the index arrest
- ICD implant post-arrest [Up to 5 years]
Whether an implantable cardioverter defibrillator was implanted post-arrest
- Cardiovascular re-hospitalization(s) [Up to 5 years]
Number of cardiovascular re-hospitalizations
- All-cause re-hospitalizations(s) [Up to 5 years]
Number of re-hospitalizations for any reason
Eligibility Criteria
Criteria
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.)
-
Prior receipt of non-study kit intravenous or intramuscular epinephrine during resuscitation
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Unity Health Toronto
- Canadian Institutes of Health Research (CIHR)
- Pfizer
Investigators
- Principal Investigator: Paul Dorian, MD, MSc, Unity Health Toronto
- Principal Investigator: Steve Lin, MD, MSc, Unity Health Toronto
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- EpiDOSE Protocol Version 2.0