- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04748991
Vernakalant Versus Amiodarone for Post-operative Atrial Fibrillation in Cardiac Surgery Patients
May 23, 2023 updated by: University of Calgary
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.
Study Overview
Status
Not yet recruiting
Conditions
Intervention / Treatment
Detailed 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.
Study Type
Interventional
Enrollment (Anticipated)
50
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Michael Chiu, MD, MSC
- Phone Number: 4032106818
- Email: michael.chiu@albertahealthservices.ca
Study Contact Backup
- Name: Vikas Kuriachan, MD
- Phone Number: 4032106818
- Email: vpkuriac@ucalgary.ca
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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.
|
Post operative AF after cardiac surgery.
Vernakalant 3mg/kg over 10 minutes followed by 2mg/kg over 10 minutes if still in AF.
Other Names:
|
Active Comparator: 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.
|
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
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rate of conversion of sustained post-operative atrial fibrillation at 90 minutes.
Time Frame: 90 minutes
|
Rate of conversion of sustained post-operative atrial fibrillation at 90 minutes.
|
90 minutes
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Duration of vasopressor therapy
Time Frame: 7 days
|
Duration of vasopressor therapy
|
7 days
|
Time to conversion to sinus rhythm
Time Frame: 7 days
|
Time to conversion to sinus rhythm
|
7 days
|
Days in intensive care unit
Time Frame: 7 Days
|
Days in intensive care unit
|
7 Days
|
Recurrence of atrial fibrillation within 48 hours
Time Frame: 48 hours
|
Recurrence of atrial fibrillation within 48 hours
|
48 hours
|
Mortality
Time Frame: 1 month
|
Mortality
|
1 month
|
LV function (Normal, Mild, Moderate or Severe)
Time Frame: 7 days
|
LV function (Normal, Mild, Moderate or Severe)
|
7 days
|
Time to initiation of beta-blockers
Time Frame: 7 days
|
Time to initiation of beta-blockers
|
7 days
|
Economics - cost of hospital stay
Time Frame: Up to one month
|
Economics - cost of hospital stay
|
Up to one month
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Michael Chiu, MD, MSC, University of Calgary
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Anticipated)
January 1, 2024
Primary Completion (Anticipated)
January 1, 2025
Study Completion (Anticipated)
September 1, 2025
Study Registration Dates
First Submitted
January 25, 2021
First Submitted That Met QC Criteria
February 8, 2021
First Posted (Actual)
February 10, 2021
Study Record Updates
Last Update Posted (Actual)
May 24, 2023
Last Update Submitted That Met QC Criteria
May 23, 2023
Last Verified
November 1, 2022
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Heart Diseases
- Cardiovascular Diseases
- Arrhythmias, Cardiac
- Atrial Fibrillation
- Molecular Mechanisms of Pharmacological Action
- Anti-Arrhythmia Agents
- Vasodilator Agents
- Enzyme Inhibitors
- Membrane Transport Modulators
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 Enzyme Inhibitors
- Sodium Channel Blockers
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors
- Potassium Channel Blockers
- Amiodarone
Other Study ID Numbers
- REB20-2257
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Study Data/Documents
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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