Clinical trial NCT04485195: RAFF4 Trial: Vernakalant vs. Procainamide for Acute Atrial Fibrillation in the Emergency Department
Official title: RAFF4 Trial: Vernakalant vs. Procainamide for Acute Atrial Fibrillation in the Emergency Department
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Atrial Fibrillation
Keywords: Emergency Department
Atrial Fibrillation
Vernakalant
Procainamide
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
First posted: 2020-07-24
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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).

Primary outcomes:
measure: Conversion to sinus rhythm for a minimum duration of 30 minutes
timeFrame: During any time following randomization until 30 minutes past the completion of the drug infusion
Secondary outcomes:
measure: Normal sinus rhythm
timeFrame: At the time of patient disposition (approximately 3 hours after arrival)
measure: Patient disposition (admission or discharge)
timeFrame: At the time of patient admission or discharge (approximately 3 hours after arrival)
measure: Length of stay in ED
timeFrame: From time of arrival until time of discharge or admission (approximately 3 hours)
measure: Time to discharge
timeFrame: From time of randomization until time of discharge or admission (approximately 3 hours)
measure: Time to conversion
timeFrame: From time of infusion start until time of conversion to sinus rhythm (approximately 0 - 90 minutes)
measure: Whether the patient required electrical cardioversion
timeFrame: From 30 minutes after the study drug infusion is completed.
measure: Adverse events
timeFrame: 0-12 hours
Other outcomes:
measure: Maintenance of normal sinus rhythm
timeFrame: 30 days post discharge
measure: Recurrence of acute AF
timeFrame: 30 days
measure: Death
timeFrame: 30 days
measure: Stroke
timeFrame: 30 days
measure: Return to normal activities
timeFrame: 30 days
Locations:
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences Centre
state: Ontario
city: Kingston
country: Canada
facility: Kingston Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: St. Michaels
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Hospital
state: Ontario
city: Laval
country: Canada
facility: Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval
state: Quebec
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Montreal
country: Canada
facility: Hopital Du Sacre-Coeur
state: Quebec
city: Quebec City
country: Canada
facility: Hopital de L'Enfant-Jesus
state: Quebec
city: Québec
country: Canada
facility: Hôtel-Dieu de Lévis
state: Quebec
Study officials:
affiliation: Ottawa Hospital Research Institute
name: Ian G Stiell, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: