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

NCT ID: NCT04485195

Last Updated: 2025-04-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 350 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-17
• Study Completion Date: 2024-11-06

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.

Conditions

Atrial Fibrillation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Vernakalant

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).

Group Type: ACTIVE_COMPARATOR

Vernakalant

Intervention Type: DRUG

an initial infusion of 3 mg/kg infused over a 10-minute period by a pre-programmed IV pump

Procainamide

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.

Group Type: ACTIVE_COMPARATOR

Procainamide

Intervention Type: DRUG

15 mg/kg in 500 mL of normal saline given over 60 minutes

Interventions

Vernakalant

an initial infusion of 3 mg/kg infused over a 10-minute period by a pre-programmed IV pump

Intervention Type: DRUG

Procainamide

15 mg/kg in 500 mL of normal saline given over 60 minutes

Intervention Type: DRUG

Other Intervention Names

BRINAVESS

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.

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).

Exclusion Criteria

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);

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ottawa Hospital Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ian G Stiell, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Ottawa Hospital Research Institute

Locations

University of Alberta Hospital

Edmonton, Alberta, Canada

Vancouver General Hospital

Vancouver, British Columbia, 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, Canada

Kingston Health Sciences Centre

Kingston, Ontario, Canada

Ottawa Hospital

Ottawa, Ontario, 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, Canada

Hopital Du Sacre-Coeur

Montreal, Quebec, Canada

Hopital de L'Enfant-Jesus

Québec, Quebec, Canada

Hôtel-Dieu de Lévis

Québec, Quebec, Canada

Countries

Canada

Other Identifiers

20200402

Identifier Type: -

Identifier Source: org_study_id