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The objective is to compare IV vernakalant to IV procainamide for the ED management of acute AF patients. If vernakalant proves to be more effective, faster, and safer than IV procainamide, this will give clinicians an important alternative for pharmacological cardioversion of acute AF. The investigators propose a pragmatic comparative effectiveness trial entailing an open label, randomized controlled trial at 12 large Canadian EDs. Study subjects will be randomized to 1 of 2 treatment arms: 1) Patients will receive an initial infusion of 3mg/kg of IV vernakalant over 10 minutes, followed by a second dose of 2mg/kg over 10 minutes, if necessary, or 2) Patients will receive a continuous infusion of 15mg/kg of IV procainamide over 60 minutes. The primary aim will be to compare conversion to normal sinus rhythm between the two drugs. The investigators will include stable patients presenting with an episode of acute AF of at least 3 hours duration, where symptoms require urgent management and where immediate cardioversion is a reasonable option. Using the integrated consent model, research assistants will obtain verbal consent from eligible patients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Vernakalant | Active Comparator | Patients randomized to this arm will receive an initial infusion of 3 mg/kg infused over a 10-minute period by a pre-programmed IV pump.82 For patients ≤ 100 kg the infusion is prepared by adding 25 mL of BRINAVESS 20 mg/mL to 100 mL of diluent creating a total volume of 125 mL at a concentration of 4 mg/mL. For patients > 100 kg the infusion is prepared by adding 30 mL of BRINAVESS 20 mg/mL to 120 mL of diluent creating a total volume of 150 mL at a concentration of 4 mg/mL. For patients weighing ≥ 113 kg, the maximum initial dose is 339 mg (84.7 mL of 4 mg/mL solution). |
|
| Procainamide | Active Comparator | Patients randomized to this arm will receive a continuous infusion of IV procainamide with a dose of 15 mg/kg in 500 mL of normal saline given over 60 minutes (maximum dose 1,500 mg), by a pre-programmed pump. While the CAEP Best Practices Checklist suggests an infusion time of 30-60 minutes, we believe that a 60-minute period will avoid some adverse events. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vernakalant | Drug | an initial infusion of 3 mg/kg infused over a 10-minute period by a pre-programmed IV pump |
|
| Measure | Description | Time Frame |
|---|---|---|
| Conversion to sinus rhythm for a minimum duration of 30 minutes | Conversion to and maintenance of sinus rhythm for at least 30 minutes at any time following randomization until 30 minutes past the completion of the drug infusion. Heart rhythm will be determined by an electrocardiogram (ECG). | During any time following randomization until 30 minutes past the completion of the drug infusion |
| Measure | Description | Time Frame |
|---|---|---|
| Normal sinus rhythm | Being in normal sinus rhythm at the time of ED disposition (discharge or admission). Heart rhythm will be determined by an electrocardiogram (ECG). | At the time of patient disposition (approximately 3 hours after arrival) |
| Patient disposition (admission or discharge) |
| Measure | Description | Time Frame |
|---|---|---|
| Maintenance of normal sinus rhythm | Maintenance of normal sinus rhythm at 30 days after ED disposition, to be verified by hospital records, patient report, or by a smartphone application. | 30 days post discharge |
| Recurrence of acute AF |
Inclusion Criteria:
The investigators will include stable (see below) patients presenting with an episode of acute non-valvular AF of at least 3 hours duration and no greater than 7 days, where symptoms require urgent management and where immediate cardioversion is a reasonable option because:
i) onset < 12 hours ago, or ii) if onset 12 - 48 hours ago and there are <2 of these CHADS-65 criteria (age ≥ 65, diabetes, hypertension, heart failure), or iii) negative for thrombus on transesophageal echocardiography. Of note, we will not exclude patients with prior episodes of acute AF. Patients will only be enrolled if the attending physician is confident about time of onset, based upon the patient's symptoms. Physicians are well aware of the importance of this determination and will not attempt to cardiovert patients otherwise.
Exclusion Criteria: The investigators will exclude patients who have any of the reasons listed below.
Appropriateness:
Safety
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| Name | Affiliation | Role |
|---|---|---|
| Ian G Stiell, MD, MSc | Ottawa Hospital Research Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alberta Hospital | Edmonton | Alberta | T6G 2B7 | Canada | ||
| Vancouver General Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41218981 | Derived | Stiell IG, Taljaard M, Eagles D, Yadav K, Vadeboncoeur A, Hohl CM, Archambault PM, Birnie D, Brown E, Campbell SG, Chen Y, Clement CM, Cournoyer A, de Wit K, Emond M, Macle L, McRae AD, Mercier E, Morris J, Mohamad G, Nemnom MJ, Nicholls SG, Pare D, Parkash R, Sivilotti M, Thavorn K, Perry JJ. Vernakalant versus procainamide for rapid cardioversion of patients with acute atrial fibrillation (RAFF4): randomised clinical trial. BMJ. 2025 Nov 11;391:e085632. doi: 10.1136/bmj-2025-085632. |
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| Procainamide | Drug | 15 mg/kg in 500 mL of normal saline given over 60 minutes |
|
Whether the patient was discharged home or admitted to the hospital. |
| At the time of patient admission or discharge (approximately 3 hours after arrival) |
| Length of stay in ED | Length of stay in ED in minutes, from time of arrival to time of discharge or admission | From time of arrival until time of discharge or admission (approximately 3 hours) |
| Time to discharge | Time to discharge in minutes, from time of randomization to time of discharge or admission | From time of randomization until time of discharge or admission (approximately 3 hours) |
| Time to conversion | Time to conversion to sinus rhythm in minutes, from time of start of study drug infusion | From time of infusion start until time of conversion to sinus rhythm (approximately 0 - 90 minutes) |
| Whether the patient required electrical cardioversion | Whether the patient required electrical cardioversion to restore normal sinus rhythm in the ED | From 30 minutes after the study drug infusion is completed. |
| Adverse events | will be classified as serious or other, whether occurring 0-2 hours or 2-12 hours after infusion, whether infusion had to be halted or discontinued, or treatment required | 0-12 hours |
Recurrence of acute atrial fibrillation requiring an emergency department visit
| 30 days |
| Death | within 30 days of ED disposition | 30 days |
| Stroke | transient ischemic attack, myocardial infarction, or other thromboembolic event within 30 days of ED disposition | 30 days |
| Return to normal activities | Return to normal daily activities measured in days | 30 days |
| Vancouver |
| British Columbia |
| V5Z 1M9 |
| Canada |
| St. Paul's Hospital | Vancouver | British Columbia | Canada |
| Queen Elizabeth II Health Sciences Centre | Halifax | Nova Scotia | Canada |
| Hamilton Health Sciences Centre | Hamilton | Ontario | l8L 2X2 | Canada |
| Kingston Health Sciences Centre | Kingston | Ontario | K2L 2V7 | Canada |
| Ottawa Hospital | Ottawa | Ontario | K1Y 4E9 | Canada |
| St. Michaels | Toronto | Ontario | Canada |
| Sunnybrook Hospital | Toronto | Ontario | Canada |
| Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval | Laval | Quebec | Canada |
| Montreal Heart Institute | Montreal | Quebec | H1T 1C8 | Canada |
| Hopital Du Sacre-Coeur | Montreal | Quebec | Canada |
| Hopital de L'Enfant-Jesus | Québec | Quebec | Canada |
| Hôtel-Dieu de Lévis | Québec | Quebec | Canada |
| ID | Term |
|---|---|
| D001281 | Atrial Fibrillation |
| D004630 | Emergencies |
| ID | Term |
|---|---|
| D001145 | Arrhythmias, Cardiac |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D020969 | Disease Attributes |
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| ID | Term |
|---|---|
| C524581 | vernakalant |
| D011342 | Procainamide |
| ID | Term |
|---|---|
| D001549 | Benzamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D062366 | para-Aminobenzoates |
| D062365 | Aminobenzoates |
| D001565 | Benzoates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
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