Epinephrine Dose: Optimal Versus Standard Evaluation Trial

Ventricular Fibrillation Clinical Trial

— EpiDOSE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03826524
• Other study ID #: EpiDOSE Protocol Version 2.2
• Status: Recruiting
• Phase: Phase 4
• Start date: May 24, 2023
• Est. completion date: June 2028

Study information

• Verified date: June 2023
• Source: Unity Health Toronto
• Contact: Theresa Aves, MSc
• Phone: 416-864-6060
• Email: theresa.aves[@]unityhealth.to
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 3790
• Est. completion date: June 2028
• Est. primary completion date: December 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiac Arrest, Out-Of-Hospital
• Death, Sudden, Cardiac
• Heart Arrest
• Out-of-Hospital Cardiac Arrest
• Sudden Cardiac Arrest
• Tachycardia
• Tachycardia, Ventricular
• Ventricular Fibrillation
• Ventricular Tachycardia-Pulseless

Intervention

Drug:
• Epinephrine
Epinephrine 1mg 1:10000 (10cc) per dose

Locations

Country	Name	City	State
Canada	Halton Region Paramedic Services	Halton	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
Unity Health Toronto	Canadian Institutes of Health Research (CIHR), Pfizer

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival to hospital discharge	Individuals discharged alive from hospital	Through study completion (up to 5 years)
Secondary	Return of spontaneous circulation in out-of-hospital setting	Return of spontaneous circulation in the field	Through study completion (up to 5 years)
Secondary	Survival to emergency department arrival	Individuals alive upon arrival to a hospital emergency department	Through study completion (up to 5 years)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	Length of stay in hospital	Length of time an individual remained in-hospital (length in days)	Through study completion (up to 5 years)
Secondary	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)
Secondary	Survival post-arrest	Survival following hospital discharge, up to 5 years	Up to 5 years
Secondary	Recurrent cardiac arrest(s)	Number of cardiac arrests following the index arrest	Up to 5 years
Secondary	ICD implant post-arrest	Whether an implantable cardioverter defibrillator was implanted post-arrest	Up to 5 years
Secondary	Cardiovascular re-hospitalization(s)	Number of cardiovascular re-hospitalizations	Up to 5 years
Secondary	All-cause re-hospitalizations(s)	Number of re-hospitalizations for any reason	Up to 5 years