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

Studies

Study First Submitted Date 2021-01-25
Study First Posted Date 2021-02-10
Last Update Posted Date 2023-05-24
Start Month Year January 2024
Primary Completion Month Year January 2025
Verification Month Year November 2022
Verification Date 2022-11-30
Last Update Posted Date 2023-05-24

Detailed Descriptions

Sequence: 20833173
Description 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. 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. 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.

Browse Interventions

Sequence: 96512196 Sequence: 96512197 Sequence: 96512198 Sequence: 96512199 Sequence: 96512200 Sequence: 96512201 Sequence: 96512202 Sequence: 96512203 Sequence: 96512204 Sequence: 96512205 Sequence: 96512206 Sequence: 96512207 Sequence: 96512208
Mesh Term Amiodarone Mesh Term Anti-Arrhythmia Agents Mesh Term Vasodilator Agents Mesh Term Potassium Channel Blockers Mesh Term Membrane Transport Modulators Mesh Term Molecular Mechanisms of Pharmacological Action Mesh Term Sodium Channel Blockers Mesh Term Cytochrome P-450 CYP1A2 Inhibitors Mesh Term Cytochrome P-450 Enzyme Inhibitors Mesh Term Enzyme Inhibitors Mesh Term Cytochrome P-450 CYP2C9 Inhibitors Mesh Term Cytochrome P-450 CYP2D6 Inhibitors Mesh Term Cytochrome P-450 CYP3A Inhibitors
Downcase Mesh Term amiodarone Downcase Mesh Term anti-arrhythmia agents Downcase Mesh Term vasodilator agents Downcase Mesh Term potassium channel blockers Downcase Mesh Term membrane transport modulators Downcase Mesh Term molecular mechanisms of pharmacological action Downcase Mesh Term sodium channel blockers Downcase Mesh Term cytochrome p-450 cyp1a2 inhibitors Downcase Mesh Term cytochrome p-450 enzyme inhibitors Downcase Mesh Term enzyme inhibitors Downcase Mesh Term cytochrome p-450 cyp2c9 inhibitors Downcase Mesh Term cytochrome p-450 cyp2d6 inhibitors Downcase Mesh Term cytochrome p-450 cyp3a inhibitors
Mesh Type mesh-list Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor

Conditions

Sequence: 52457101 Sequence: 52457102
Name Atrial Fibrillation Name Post-cardiac Surgery
Downcase Name atrial fibrillation Downcase Name post-cardiac surgery

Id Information

Sequence: 40363275
Id Source org_study_id
Id Value REB20-2257

Design Groups

Sequence: 55911116 Sequence: 55911117
Group Type Experimental Group Type Active Comparator
Title Intravenous Vernakalant Title Intravenous Amiodarone
Description 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. Description 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.

Interventions

Sequence: 52767183 Sequence: 52767184
Intervention Type Drug Intervention Type Drug
Name Vernakalant Name Amiodarone
Description Post operative AF after cardiac surgery. Vernakalant 3mg/kg over 10 minutes followed by 2mg/kg over 10 minutes if still in AF. Description 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

Keywords

Sequence: 80256549 Sequence: 80256550
Name Amiodarone Name Vernakalant
Downcase Name amiodarone Downcase Name vernakalant

Design Outcomes

Sequence: 178453129 Sequence: 178453130 Sequence: 178453131 Sequence: 178453132 Sequence: 178453133 Sequence: 178453128 Sequence: 178453134 Sequence: 178453135 Sequence: 178453136
Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type primary Outcome Type secondary Outcome Type secondary Outcome Type secondary
Measure Duration of vasopressor therapy Measure Time to conversion to sinus rhythm Measure Days in intensive care unit Measure Recurrence of atrial fibrillation within 48 hours Measure Mortality Measure Rate of conversion of sustained post-operative atrial fibrillation at 90 minutes. Measure LV function (Normal, Mild, Moderate or Severe) Measure Time to initiation of beta-blockers Measure Economics – cost of hospital stay
Time Frame 7 days Time Frame 7 days Time Frame 7 Days Time Frame 48 hours Time Frame 1 month Time Frame 90 minutes Time Frame 7 days Time Frame 7 days Time Frame Up to one month
Description Duration of vasopressor therapy Description Time to conversion to sinus rhythm Description Days in intensive care unit Description Recurrence of atrial fibrillation within 48 hours Description Mortality Description Rate of conversion of sustained post-operative atrial fibrillation at 90 minutes. Description LV function (Normal, Mild, Moderate or Severe) Description Time to initiation of beta-blockers Description Economics – cost of hospital stay

Browse Conditions

Sequence: 194578708 Sequence: 194578709 Sequence: 194578710 Sequence: 194578711 Sequence: 194578712
Mesh Term Atrial Fibrillation Mesh Term Arrhythmias, Cardiac Mesh Term Heart Diseases Mesh Term Cardiovascular Diseases Mesh Term Pathologic Processes
Downcase Mesh Term atrial fibrillation Downcase Mesh Term arrhythmias, cardiac Downcase Mesh Term heart diseases Downcase Mesh Term cardiovascular diseases Downcase Mesh Term pathologic processes
Mesh Type mesh-list Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor

Sponsors

Sequence: 48585106
Agency Class OTHER
Lead Or Collaborator lead
Name University of Calgary

Overall Officials

Sequence: 29434992
Role Principal Investigator
Name Michael Chiu, MD, MSC
Affiliation University of Calgary

Central Contacts

Sequence: 12082608 Sequence: 12082609
Contact Type primary Contact Type backup
Name Michael Chiu, MD, MSC Name Vikas Kuriachan, MD
Phone 4032106818 Phone 4032106818
Email michael.chiu@albertahealthservices.ca Email vpkuriac@ucalgary.ca
Role Contact Role Contact

Design Group Interventions

Sequence: 68541070 Sequence: 68541071
Design Group Id 55911116 Design Group Id 55911117
Intervention Id 52767183 Intervention Id 52767184

Eligibilities

Sequence: 30929505
Gender All
Minimum Age 18 Years
Maximum Age N/A
Healthy Volunteers No
Criteria Inclusion Criteria: Age >/=18 years 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. Hemodynamically stable with/without vasopressor support Exclusion Criteria: LVAD insertion or heart transplantation MAZE procedure Transcatheter aortic valve replacement (TAVR) History of or planned mechanical valve replacement Rheumatic heart disease Congenital cardiac defect (excluding bicuspid aortic valve or patent foramen ovale) History of prior atrial fibrillation or flutter History of ablation for atrial fibrillation 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 Received amiodarone within 6 weeks 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. Return to OR during CVICU stay or readmission to CIVCU from Cardiac Surgery ward.
Adult True
Child False
Older Adult True

Calculated Values

Sequence: 254209109
Registered In Calendar Year 2021
Were Results Reported False
Has Single Facility False
Minimum Age Num 18
Minimum Age Unit Years
Number Of Primary Outcomes To Measure 1
Number Of Secondary Outcomes To Measure 8

Designs

Sequence: 30675156
Allocation Randomized
Intervention Model Parallel Assignment
Observational Model
Primary Purpose Treatment
Time Perspective
Masking None (Open Label)
Intervention Model Description 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.

Intervention Other Names

Sequence: 26816081 Sequence: 26816082
Intervention Id 52767183 Intervention Id 52767184
Name BRINAVESS Name Cordarone, Nexterone, Pacerone

Responsible Parties

Sequence: 29041885
Responsible Party Type Sponsor

Study References

Sequence: 52366858 Sequence: 52366859 Sequence: 52366860
Pmid 18332267 Pmid 19948506 Pmid 21232669
Reference Type background Reference Type background Reference Type background
Citation 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. Citation 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. Citation 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.

Documents

Sequence: 715673 Sequence: 715674
Document Type Product monograph – Vernakalant Document Type Product monograph – Amiodarone
Url https://pdf.hres.ca/dpd_pm/00038441.PDF Url https://pdf.hres.ca/dpd_pm/00035425.PDF