RAFF4 Trial: Vernakalant vs. Procainamide for Acute Atrial Fibrillation in the Emergency Department

Atrial Fibrillation Clinical Trial

Official title:

RAFF4 Trial: Vernakalant vs. Procainamide for Acute Atrial Fibrillation in the Emergency Department

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04485195
• Other study ID #: 20200402
• Status: Recruiting
• Phase: Phase 4
• Start date: June 17, 2021
• Est. completion date: June 1, 2024

Study information

• Verified date: September 2023
• Source: Ottawa Hospital Research Institute
• Contact: Ian G Stiell, MD, MSc
• Phone: 613-798-5555
• Email: istiell[@]ohri.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 340
• Est. completion date: June 1, 2024
• Est. primary completion date: September 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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:

1. The patient has been adequately anticoagulated for a minimum of 3 weeks (warfarin and INR > 2.0 or novel oral anticoagulants [dabigatran, rivaroxaban, edoxaban, and apixaban]), or

2. The patient is not adequately anticoagulated for > 3 weeks, has no history of stroke or TIA, and does not have valvular heart disease, AND:

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.

1. Appropriateness:

1. unable to understand the study and integrated consent due to language barrier and/or cognitive impairment;

2. have permanent (chronic) AF;

3. have valvular heart disease (mitral stenosis, rheumatic or mechanical);

4. increased risk of stroke because onset not clearly <48 hours and not anticoagulated (or abnormal TEE); or do not meet the inclusion criteria a or b;

5. deemed unstable and require immediate cardioversion: i) systolic blood pressure <100 mmHg; ii) rapid ventricular preexcitation (Wolff-Parkinson-White syndrome); iii) acute coronary syndrome - chest pain and acute ischemic changes on ECG; or iv) pulmonary edema - severe dyspnea requiring immediate IV diuretic, nitrates, or BIPAP;

6. primary presentation was for another condition; examples include pneumonia, pulmonary embolism, and sepsis;

7. convert spontaneously to sinus rhythm prior to randomization;

8. were previously enrolled in the study; or

9. have atrial flutter.

2. Safety

1. has heart failure Class NYHA III or NYHA IV; left ventricular ejection fraction <30%; or has clinical or radiological evidence of acute HF;

2. has presented with an acute coronary syndrome or acute decompensated heart failure, in the last 30 days; or has had a recent myocardial infarction (< 3 months);

3. has severe aortic stenosis;

4. has a systolic blood pressure < 100 mmHg;

5. has a significantly prolonged QT interval at baseline e.g. uncorrected > 440 msec, congenital or acquired long QT syndrome; or a family history of Long QT syndrome; or ECG shows QTc >460ms (when heart rate >100 measured by the Fridericia formula);

6. has severe bradycardia (heart rate < 55 bpm), sinus node dysfunction, or second or third degree atrioventricular heart block, in the absence of an in situ properly functioning pacemaker; or, has Brugada syndrome (genetic disease with increased risk of sudden cardiac death);

7. has received an intravenous antiarrhythmic drug Class I, e.g. procainamide, or Class Ill, e.g. amiodarone or ibutilide, within the prior 4 hours; or currently takes oral class I or III antiarrhythmic drugs other than amiodarone (last dose < 5 half-lives before enrollment);

8. has received an IV beta-blocker within the 2 hours prior

9. has hypersensitivity to the active substance or to any of the ingredients of either drug;

10. has advanced or end-stage liver disease; or

11. is breast feeding or pregnant (safety not established).

Related Conditions & MeSH terms

• Atrial Fibrillation
• Emergencies

Intervention

Drug:
• Vernakalant
an initial infusion of 3 mg/kg infused over a 10-minute period by a pre-programmed IV pump
• Procainamide
15 mg/kg in 500 mL of normal saline given over 60 minutes

Locations

Country	Name	City	State
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia
Canada	Hamilton Health Sciences Centre	Hamilton	Ontario
Canada	Kingston Health Sciences Centre	Kingston	Ontario
Canada	Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval	Laval	Quebec
Canada	Hopital Du Sacre-Coeur	Montreal	Quebec
Canada	Montreal Heart Institute	Montreal	Quebec
Canada	Ottawa Hospital	Ottawa	Ontario
Canada	Hôtel-Dieu de Lévis	Québec	Quebec
Canada	Hopital de L'Enfant-Jesus	Quebec City	Quebec
Canada	St. Michaels	Toronto	Ontario
Canada	Sunnybrook Hospital	Toronto	Ontario
Canada	St. Paul's Hospital	Vancouver	British Columbia
Canada	Vancouver General Hospital	Vancouver	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Ottawa Hospital Research Institute

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	Recurrence of acute AF	Recurrence of acute atrial fibrillation requiring an emergency department visit	30 days
Other	Death	within 30 days of ED disposition	30 days
Other	Stroke	transient ischemic attack, myocardial infarction, or other thromboembolic event within 30 days of ED disposition	30 days
Other	Return to normal activities	Return to normal daily activities measured in days	30 days
Primary	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
Secondary	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)
Secondary	Patient disposition (admission or discharge)	Whether the patient was discharged home or admitted to the hospital.	At the time of patient admission or discharge (approximately 3 hours after arrival)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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.
Secondary	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