Vernakalant Versus Amiodarone for Post-operative Atrial Fibrillation in Cardiac Surgery Patients

NCT ID: NCT04748991

Last Updated: 2024-05-22

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-30
• Study Completion Date: 2025-09-30

Brief Summary

Post-operative atrial fibrillation is a common problem post cardiac surgery with rates exceeding 30%. Atrial fibrillation has multiple adverse effects on cardiac hemodynamics and can lead to hypotension, diminished end organ perfusion and lengthen the stay in ICU. Amiodarone is the medication of choice used for pharmacological cardioversion and can be used with vasoactive medications. Intravenous amiodarone is associated with hypotension and end organ perfusion requiring escalation in vasoactive support. Vernakalant is novel anti-arrhythmic agent approved in Canada for cardioversion of atrial fibrillation that primarily works on atrial channels and has no effect on contractility or vasodilation. Clinical trials have proved good efficacy of Vernakalant in conversion of paroxysmal atrial fibrillation however there is no comparison of Amiodarone to Vernakalant in post-operative cardiac surgery. We plan to perform a clinical trial comparing Vernakalant to amiodarone in post-cardiac surgery patients with a primary outcome of cardioversion at 90 minutes. Secondary outcomes will follow duration of vasoactive medications, days in ICU and economics.

Detailed Description

1. Background - Atrial fibrillation (AF) is the most common cardiac arrhythmia post cardiac surgery. Estimates suggest that rates of patients experiencing post-operative atrial fibrillation (POAF) after cardiac surgery exceeds 30%. Atrial fibrillation has multiple effects on the cardiopulmonary hemodynamics. Rapid irregular ventricular rate results in decreased coronary flow diminishing the ability to preserve myocardial oxygen demand leading to ischemia. Atrial contraction provides 15-20% of LV filling in normal cardiac physiology and loss of synchronized atrial contraction in addition to decreased diastolic filling time may lead to decreased cardiac. This may lead to hypotension and diminished end organ perfusion requiring additional vasoactive support. Currently amiodarone is utilized as the pharmacological agent of choice for POAF in cardiac surgery, typical rate control agents are contraindicated due to need of vasoactive requirements. However direct effects of IV amiodarone include vasodilation and hypotension typically requiring escalating doses of vasoactive medications, which subsequently prolong stay in the CVICU (cardiovascular Intensive Care Unit), increase exposure to vasopressors and potentially mechanical ventilation. Vernakalant is a Von Williams Class III novel anti-arrhythmic agent with primary activity on atrial tissue with limited activity on ventricular myocardium. Primary mechanism of action is blocking early activating K+ atrial channels and frequency-dependent atrial Na+ channels which prolongs atrial refractory periods and decreasing atrial conduction without promoting ventricular arrhythmia. There have been many trials that proven efficacy in converting AF in patients with atrial fibrillation and in the post cardiac surgery patients, however this has never been compared to standard of care Amiodarone.

2. Research Questions and objectives: We hypothesize administration of vernakalant compared to amiodarone will have a higher rate of cardioversion to sinus rhythm at 90 min in post-operative sustained atrial fibrillation. This will reduce duration of vasoactive medications, days in ICU and mortality.

3. Methods: Patients will be recruited from the CVICU 24 hours after admission to CIVCU based on inclusion and exclusion criteria. Patients identified with new presentation atrial fibrillation with a sustained duration of greater than 30 minutes will be considered for the study. Patients will be randomized to Amiodarone versus Vernakalant using a computerized process. Patients randomized to an amiodarone arm will receive 150mg IV bolus and an amiodarone infusion of 1mg/hr x 6 hours followed by 0.5mg/hr x 12 hours. Patients randomized to Vernakalant will receive a bolus of 3mg/kg over 10 minutes and an observation period of 15 minutes, if the patient is still in AF, they will receive an additional 2.0mg/kg bolus of Vernakalant. Infusions will be discontinued if QT interval becomes >550ms, heart rate less than 45 bpm lasting >30 seconds with symptoms or <40bpm lasting >30 seconds with or without symptoms, ventricular tachycardia or development of heart block. At 90 minutes rate of conversion to sinus rhythm will be documented. Secondary outcomes including time to AF conversion, recurrence of atrial fibrillation will be documented along with safety events over 48h. Duration of vasoactive medications, days in ICU, time to initiation of beta blockers, mortality, Left Ventricular (LV) function and economics of ICU still will be followed. Patients will be excluded if they return to the OR.

Conditions

Atrial Fibrillation; Post-cardiac Surgery

Study Design

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

Study Groups

Intravenous Vernakalant

Patients randomized to Vernakalant will receive a bolus of 3mg/kg over 10 minutes and an observation period of 15 minutes, if the patient is still in AF, they will receive an additional 2.0mg/kg bolus of Vernakalant.

Group Type: EXPERIMENTAL

Vernakalant

Intervention Type: DRUG

Post operative AF after cardiac surgery. Vernakalant 3mg/kg over 10 minutes followed by 2mg/kg over 10 minutes if still in AF.

Intravenous Amiodarone

Patients randomized to an amiodarone arm will receive 150mg IV bolus and an amiodarone infusion of 1mg/hr x 6 hours followed by 0.5mg/hr x 12 hours.

Group Type: ACTIVE_COMPARATOR

Amiodarone

Intervention Type: DRUG

Post operative AF after cardiac surgery. Amiodarone 150mg IV followed by 1 mg/min x 6 hours then 0.5 mg/min x 12 hours

Interventions

Vernakalant

Post operative AF after cardiac surgery. Vernakalant 3mg/kg over 10 minutes followed by 2mg/kg over 10 minutes if still in AF.

Intervention Type: DRUG

Amiodarone

Post operative AF after cardiac surgery. Amiodarone 150mg IV followed by 1 mg/min x 6 hours then 0.5 mg/min x 12 hours

Intervention Type: DRUG

Other Intervention Names

BRINAVESS; Cordarone, Nexterone, Pacerone

Eligibility Criteria

Inclusion Criteria

1. Age >/=18 years

2. Undergone heart surgery for coronary artery bypass surgery (on-pump or off-pump CABG) and/or valve repair or replacement (excluding mechanical valves), including re-operations.

3. Hemodynamically stable with/without vasopressor support

Exclusion Criteria

1. LVAD insertion or heart transplantation

2. MAZE procedure

3. Transcatheter aortic valve replacement (TAVR)

4. History of or planned mechanical valve replacement

5. Rheumatic heart disease

6. Congenital cardiac defect (excluding bicuspid aortic valve or patent foramen ovale)

7. History of prior atrial fibrillation or flutter

8. History of ablation for atrial fibrillation

9. Contraindication to amiodarone

• PR >240ms
• Heart block (2nd or 3rd degree)
• QTC >480ms
• Untreated thyroid disorder
• AST or ALT >2x upper limit of normal
• Hepatic cirrhosis
• Interstitial lung disease

10. Received amiodarone within 6 weeks

11. Contraindications to Vernakalant

• Known hypersensitivity to Vernakalant
• Prolonged QT
• Heart block (2nd or 3rd degree)
• Use of anti-arrhythmic medication in the past 4 weeks.

12. Return to OR during CVICU stay or readmission to CIVCU from Cardiac Surgery ward.

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

Sponsors

University of Calgary

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Chiu, MD, MSC

Role: PRINCIPAL_INVESTIGATOR

University of Calgary

Central Contacts

Michael Chiu, MD, MSC

Role: CONTACT

michael.chiu@albertahealthservices.ca

4032106818

Vikas Kuriachan, MD

Role: CONTACT

vpkuriac@ucalgary.ca

4032106818

References

Roy D, Pratt CM, Torp-Pedersen C, Wyse DG, Toft E, Juul-Moller S, Nielsen T, Rasmussen SL, Stiell IG, Coutu B, Ip JH, Pritchett EL, Camm AJ; Atrial Arrhythmia Conversion Trial Investigators. Vernakalant hydrochloride for rapid conversion of atrial fibrillation: a phase 3, randomized, placebo-controlled trial. Circulation. 2008 Mar 25;117(12):1518-25. doi: 10.1161/CIRCULATIONAHA.107.723866. Epub 2008 Mar 10.

Reference Type: BACKGROUND

PMID: 18332267 (View on PubMed)

Kowey PR, Dorian P, Mitchell LB, Pratt CM, Roy D, Schwartz PJ, Sadowski J, Sobczyk D, Bochenek A, Toft E; Atrial Arrhythmia Conversion Trial Investigators. Vernakalant hydrochloride for the rapid conversion of atrial fibrillation after cardiac surgery: a randomized, double-blind, placebo-controlled trial. Circ Arrhythm Electrophysiol. 2009 Dec;2(6):652-9. doi: 10.1161/CIRCEP.109.870204.

Reference Type: BACKGROUND

PMID: 19948506 (View on PubMed)

Camm AJ, Capucci A, Hohnloser SH, Torp-Pedersen C, Van Gelder IC, Mangal B, Beatch G; AVRO Investigators. A randomized active-controlled study comparing the efficacy and safety of vernakalant to amiodarone in recent-onset atrial fibrillation. J Am Coll Cardiol. 2011 Jan 18;57(3):313-21. doi: 10.1016/j.jacc.2010.07.046.

Reference Type: BACKGROUND

PMID: 21232669 (View on PubMed)

Study Documents

Document Type: Product monograph - Vernakalant

View Document

Document Type: Product monograph - Amiodarone

View Document

Other Identifiers

REB20-2257

Identifier Type: -

Identifier Source: org_study_id