Vernakalant Versus Flecainide: Atrial Contractility

Effects of Vernakalant and Flecainide on Atrial Contractility in Patients With Atrial Fibrillation

Atrial fibrillation (AF) is associated with decreased atrial contractility which is associated with stroke. Decreased contractility becomes apparent after cardioversion of atrial fibrillation, a short period (weeks) during which stroke risk is increased. Improved contractility immediately after cardioversion may prevent arrhythmia progression. In addition, it may reduce the stroke risk. Vernakalant is a new antiarrhythmic drug able to convert atrial fibrillation to sinus rhythm and at the same time increase atrial contractility. The latter has not yet been shown in humans and is subject of the present investigation. Our hypothesis is that in humans the contractility of the atria is higher after administration of vernakalant compared to flecainide. If indeed vernakalant improves atrial contractility after cardioversion further studies into the effect on long-term arrhythmia progression and stroke prevention may follow.

Study Overview

• Status: Unknown
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: Flecainide; Drug: Vernakalant

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ione Limantoro, MD; Phone Number: +31433875119; Email: ione.limantoro@mumc.nl
• Study Contact Backup: Name: Harry Crijns, MD, PhD; Phone Number: +31433875093; Email: hjgm.crijns@mumc.nl

Study Locations

• Netherlands
  • Maastricht, Netherlands, 6229 HX
    • Maastricht University Hospital
    • Contact: Ione Limantoro, MD; Phone Number: +31433875119; Email: ione.limantoro@mumc.nl
    • Contact: Harry Crijns, MD, PhD; Phone Number: +31433875093; Email: hjmg.crijns@mumc.nl
    • Principal Investigator: Harry Crijns, MD, PhD
    • Sub-Investigator: Ione Limantoro, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• persistent AF or paroxysmal AF
• eligible for treatment with vernakalant or flecainide infusion to restore sinus rhythm
• receiving adequate anticoagulant therapy (or having an episode of AF lasting < 24 hours)

Exclusion Criteria:

• refusal or inability to give informed consent to participate in this study
• atrial flutter
• contra-indications for receiving vernakalant or flecainide according to MUMC+ protocol (unstable hemodynamic condition, LVEF < 40%, inadequate potassium levels, acute ischaemia, sinus node dysfunction)
• age < 18 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Flecainide; Patients randomized to flecainide will receive a 10-minute infusion of 2 mg/kg (maximal 150 mg) flecainide. If the patient is still in AF 1 hour after the infusion, electrical cardioversion will be performed according to protocol.	Drug: Flecainide; 10-minute infusion of 2 mg/kg (maximal 150 mg); Other Names: Tambocor, EV product code SUB13894MIG
Active Comparator: Vernakalant; Patients randomized to vernakalant will receive a 10-minute infusion of 3 mg/kg vernakalant, followed by a 15 minute observation period. If the patient is still in atrial fibrillation, an additional 10-minute infusion of 2 mg/kg vernakalant will be given. If the patient is still in AF 1 hour after the infusion, electrical cardioversion will be performed according to protocol.	Drug: Vernakalant; 10-minute infusion of 3 mg/kg vernakalant, followed by a 15 minute observation period. If the patient is still in atrial fibrillation, an additional 10-minute infusion of 2 mg/kg vernakalant will be given.; Other Names: Brinavess, EV product code SUB30707

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Atrial contractility measured by echocardiography	Echocardiography will be performed when the patient has sinus rhythm. Transmitral flow will be measured by pulsed Doppler from an apical four chamber view. Peak velocities of the early filling (E) wave and atrial filling (A) will be determined. We will also determine the E/A ratio and the atrial volumes and the total atrial conduction time (PA-TVI).	After successful cardioversion to sinus rhythm (this can be during infusion of medication or during the first hour after infusion) an echocardiography will be performed within one hour.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Conversion to sinus rhythm	Heart rhythm will be assessed on monitor and confirmed on ECG.	Within one hour after drug administration
Recurrence of AF	Heart rhythm will be assessed by ECG.	At one month follow-up

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Investigators: Principal Investigator: Harry Crijns, MD, PhD, Maastricht University Hospital

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Anticipated): August 1, 2013
• Study Completion (Anticipated): August 1, 2013

Study Registration Dates

• First Submitted: July 9, 2012
• First Submitted That Met QC Criteria: July 18, 2012
• First Posted (Estimate): July 20, 2012

Study Record Updates

• Last Update Posted (Estimate): July 20, 2012
• Last Update Submitted That Met QC Criteria: July 18, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: Atrial fibrillation; Echocardiography; Vernakalant; Flecainide
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Membrane Transport Modulators; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Flecainide
• Other Study ID Numbers: NL39854.068.12