DOuble SEquential External Defibrillation for Refractory VF

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Out-Of-Hospital Cardiac Arrest, Ventricular Fibrillation

Intervention / Treatment
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* Procedure: Double Sequential Defibrillation
* Procedure: Vector Change Defibrillation


Participation Criteria
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Eligibility Criteria
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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.

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: Crossover Assignment
Interventional Model Description: This is a cluster randomized trial, with cluster units defined by EMS agency. Each cluster will crossover at six month intervals for each EMS agency during the study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard Arm<br>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<br>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<br>* Defibrillation using pad placement in anterior-posterior position<br>|
| Active Comparator: Vector Change Defibrillation<br>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<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Resuscitation, Arrhythmia, Cardiac, Heart Diseases, Heart Arrest