DOuble SEquential External Defibrillation for Refractory VF (DOSEVF)

DOuble SEquential External Defibrillation for Refractory Ventricular Fibrillation (DOSEVF) Randomized Controlled Trial

Despite significant advances in resuscitation efforts, there are some patients who remain in refractory ventricular fibrillation (VF) during out-of-hospital cardiac arrest. Double sequential external defibrillation (DSED) and vector change defibrillation have been proposed as viable options for patients in refractory VF. This cluster randomized trial will compare (1) continued resuscitation using standard defibrillation; (2) resuscitation involving DSED; or (3) resuscitation involving vector change defibrillation, in patients presenting with refractory VF during out-of-hospital cardiac arrest. The results of this study will provide high level evidence of the impact of both DSED and vector change defibrillation on ROSC and patient survival after OHCA.

Study Overview

• Status: Completed
• Conditions: Ventricular Fibrillation; Out-Of-Hospital Cardiac Arrest
• Intervention / Treatment: Procedure: Double Sequential Defibrillation; Procedure: Vector Change Defibrillation

Detailed Description

Double sequential external defibrillation (DSED) and vector change defibrillation have been proposed as viable options for patients in refractory ventricular fibrillation (VF) during out-of-hospital cardiac arrest. However, currently there is insufficient evidence to support widespread implementation of this therapy. As such, a well-designed randomized controlled trial (RCT) employing a standardized approach to alternative defibrillation strategies early in the treatment of refractory VF is required to determine whether these treatments may impact clinical outcomes. This cluster randomized trial will be conducted in the regions of Peel, Halton, Simcoe, and the cities of London, Ottawa, and Toronto, Ontario, Canada over a three year time period. All adult (≥ 18 years) patients presenting in refractory VF/pulseless ventricular tachycardia (pVT) (defined as patients presenting in VF/pVT and remaining in VF/pVT after three consecutive standard defibrillation attempts each separated by 2 minutes of CPR) during out-of-hospital cardiac arrest of presumed cardiac etiology will be assigned to be treated by one of three strategies: (1) continued resuscitation using standard defibrillation; (2) resuscitation involving DSED (two defibrillators, one using anterior-posterior pad placement and the second using anterior- anterior pad placement delivering two rapid sequential shocks for all subsequent defibrillation attempts); or (3) resuscitation involving vector change (change of defibrillation pads from anterior-anterior to an anterior-posterior pad position) defibrillation. All study arms will continue to receive antiarrhythmic use and epinephrine as per current provincial standards. The cluster units will be defined by emergency medical service (EMS) agency and each cluster will crossover at 6 month intervals throughout the duration of the study.

• Study Type: Interventional
• Enrollment (Actual): 405
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Brampton, Ontario, Canada
      • Peel Regional Paramedic Service
    • London, Ontario, Canada
      • Middlesex-London Paramedic Service
    • Oakville, Ontario, Canada
      • Halton Region Paramedic Services
    • Ottawa, Ontario, Canada
      • Ottawa Paramedic Service
    • Simcoe, Ontario, Canada
      • County of Simcoe Paramedic Services
    • Toronto, Ontario, Canada
      • Toronto Paramedic Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ≥ 18 years of age
• Non-traumatic cardiac arrest of presumed cardiac etiology
• Presenting rhythm of ventricular fibrillation or pulseless ventricular tachycardia
• No ROSC or non-shockable rhythm after three consecutive shocks by EMS or fire department.

Exclusion Criteria:

• Traumatic cardiac arrest
• Patients with pre-existing do not resuscitate orders
• Patients without VF or pulseless VT as presenting rhythm
• Patients without three consecutive shocks delivered
• Patients initially treated by non-participating fire or EMS agencies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard Arm; All defibrillation attempts will occur using the standard defibrillation method, i.e. defibrillation pads will be placed in the anterior-anterior configuration. The patient may also be administered antiarrythmic agents and epinephrine, as per current provincial standard.
Active Comparator: Double Sequential Defibrillation; The first three shocks will occur with defibrillation pads placed in the anterior-anterior position. For all further shocks, a second set of defibrillation pads (via a second on scene EMS or fire defibrillator) will be applied in the anterior-posterior position, and defibrillation will be carried out by sequential defibrillation shocks provided by the two defibrillators (i.e. with a short delay between the two defibrillators). The patient may also be administered antiarrythmic agents and epinephrine, as per current provincial standard.	Procedure: Double Sequential Defibrillation; Defibrillation using pad placement in anterior-posterior position
Active Comparator: Vector Change Defibrillation; The first three shocks will occur with defibrillation pads placed in the anterior-anterior position. All further shocks will occur with the pads placed in the anterior-posterior position. The patient may also be administered antiarrythmic agents and epinephrine, as per current provincial standard.	Procedure: Vector Change Defibrillation; Defibrillation using two defibrillators, one with pad placement in anterior-posterior position and the other with pad placement in anterior-anterior position delivering two rapid sequential shocks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival to Hospital Discharge	Binary outcome of whether the patient was discharged alive from hospital or died prior to discharge.	Through study completion of three years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurologic outcome	Neurologic outcome as defined by the modified Rankin Scale at time of hospital discharge. mRS 0-2 will be considered a good neurologic outcome.	Throughout study completion of three years
Return of Spontaneous Circulation	Binary outcome of whether or not a patient had a return of spontaneous circulation	1 Day
VF termination after first interventional shock	Cessation of the VF waveform on defibrillator monitor at first rhythm analysis post interventional or standard shock. The interpretation will occur after three standard shocks have failed to terminate VF	1 Day
VF Termination after all interventional shocks	Cessation of the VF waveform on defibrillator monitor at any rhythm analysis post interventional or standard shock. The interpretation will occur after three standard shocks have failed to terminate VF	1 Day
Number of defibrillation attempts to achieve Return of spontaneous circulation	Total number of shocks required to achieve the first return of spontaneous circulation during resuscitation, inclusive of the first three standard shocks	1 Day

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Collaborators: London Health Sciences Centre; Toronto Paramedic Services; Halton Region Paramedic Services; County of Simcoe Paramedic Services; Peel Regional Paramedic Services; Middlesex-London EMS; Ottawa Paramedic Service
• Investigators: Principal Investigator: Sheldon Cheskes, MD, Sunnybrook Centre for Prehospital Medicine

Publications and helpful links

General Publications

• Drennan IR, Dorian P, McLeod S, Pinto R, Scales DC, Turner L, Feldman M, Verbeek PR, Morrison LJ, Cheskes S. DOuble SEquential External Defibrillation for Refractory Ventricular Fibrillation (DOSE VF): study protocol for a randomized controlled trial. Trials. 2020 Nov 26;21(1):977. doi: 10.1186/s13063-020-04904-z.
• Cheskes S, Dorian P, Feldman M, McLeod S, Scales DC, Pinto R, Turner L, Morrison LJ, Drennan IR, Verbeek PR. Double sequential external defibrillation for refractory ventricular fibrillation: The DOSE VF pilot randomized controlled trial. Resuscitation. 2020 May;150:178-184. doi: 10.1016/j.resuscitation.2020.02.010. Epub 2020 Feb 19.
• Cheskes S, Verbeek PR, Drennan IR, McLeod SL, Turner L, Pinto R, Feldman M, Davis M, Vaillancourt C, Morrison LJ, Dorian P, Scales DC. Defibrillation Strategies for Refractory Ventricular Fibrillation. N Engl J Med. 2022 Nov 24;387(21):1947-1956. doi: 10.1056/NEJMoa2207304. Epub 2022 Nov 6.

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2019
• Primary Completion (Actual): August 1, 2022
• Study Completion (Actual): August 1, 2022

Study Registration Dates

• First Submitted: August 30, 2019
• First Submitted That Met QC Criteria: September 4, 2019
• First Posted (Actual): September 6, 2019

Study Record Updates

• Last Update Posted (Actual): September 22, 2022
• Last Update Submitted That Met QC Criteria: September 20, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Heart Diseases; Heart Arrest; Resuscitation; Arrhythmia, Cardiac
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Heart Arrest; Ventricular Fibrillation; Out-of-Hospital Cardiac Arrest
• Other Study ID Numbers: DOSEVF RCT

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