Predictive Factors to Effectively Terminate Paroxysmal Atrial Fibrillation by Blocking Atrial Selective Ionic Currents

NCT03005366 | Completed Phase 4 DMC

• 1 other identifier: SELECTI-CARFAP
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

• The main objective of this project is to study the efficacy and the mechanistic value of blocking both atrial specific and atria-preferential dynamics of ionic currents to terminate paroxysmal atrial fibrillation (AF).
• The hypothesis is that a drug blocking atrial specific and atria-preferential dynamics of ionic currents (IK,ACh - acetylcholine sensitive K+ current - and INa - inward sodium current - , respectively) will be more effective to terminate paroxysmal AF episodes with fast atrial activation rates, than a classical INa blocker, which will be more effective to terminate AF episodes with slower activation rates.
• The investigators will include patients without structural heart disease and short-lasting AF episodes (\<48 h.). Double blind and single center study, in which patients will be randomly assigned to a cardioversion group using intravenous flecainide or to an atria-preferential and atrial-specific blockade group using intravenous vernakalant. Patients will be routinely monitored in the electrophysiology room to acquire both 12-lead digitized ECG signals and non-invasive body surface potential mapping. Atrial signals will be extracted from both the multisite body surface and ECG recordings to obtain temporal and spectral parameters, and measure organization and atrial rate in both groups. The results obtained in the clinical setting will be studied in mathematical models to understand their capability to terminate paroxysmal AF. The project expects to provide consistent, reliable and reproducible parameters that will assist clinicians to know what type of paroxysmal AF episodes will be more suitable to effectively terminate, upon administration of drugs with an atrial specific and atria-preferential profile.

Conditions

Paroxysmal Atrial Fibrillation

Keywords

Atrial fibrillation; vernakalant; flecainide; cardioversion

Outcome Measures

Primary Outcomes (1)

• Electrocardiographic-based spectral parameters of atrial fibrillatory activity (Dominant frequency) associated with successful or unsuccessful cardioversion in both groups of patients.

  The investigators will quantify the difference in baseline dominant frequency values (Hz) of atrial fibrillatory activity between patients with successful cardioversion in the vernakalant and flecainide groups. The investigators will also quantify the difference in baseline dominant frequency values (Hz) of atrial fibrillatory activity between patients with successful and unsuccessful cardioversion within the vernakalant or flecainide group.

  18 months

Secondary Outcomes (5)

• Cardioversion success (yes/no) in patients with paroxysmal atrial fibrillation episodes lasting < 24 hours or ≥24 hours.

  18 months

• Electrocardiographic-based spectral parameters of atrial fibrillatory activity (Dominant frequency) in patients with episodes lasting < 24 hours or ≥24 hours.

  18 months

• Spectral parameters of atrial fibrillatory activity (Dominant frequency) recorded by non-invasive body surface potential mapping associated with successful or unsuccessful cardioversion in both groups of patients.

  24 months

• Effects on reentrant-based atrial fibrillation (dominant frequency decrease, rotor meandering) in 2D models of fast and low atrial activation rates under the effect of vernakalant or flecainide.

  24 months

• Atrial Fibrillation Quality of Life questionnaire (AF-QOL).

  24 months

Other Outcomes (1)

• Patient's perception during cardioversion. The investigators will used a custom-designed five-question questionnaire as follows:

  24 months

Study Arms (2)

Flecainide

ACTIVE COMPARATOR

Conventional cardioversion group using intravenous flecainide.

Drug: Flecainide

Vernakalant

ACTIVE COMPARATOR

Atria-preferential and atrial-specific blockade group using intravenous vernakalant.

Drug: Vernakalant

Interventions

Vernakalant DRUG

Initial infusion: 3 mg/kg intravenously over a 10 minute period. For patients weighing ≥ 113 kg, the maximum initial dose will be 339 mg. If conversion to sinus rhythm does not occur within 15 minutes after the end of the initial infusion, a second 10 minute infusion of 2 mg/kg will be administered. For patients weighing ≥ 113 kg, the maximum second infusion will be 226 mg.

Also known as: BRINAVESS

Vernakalant

Flecainide DRUG

2 mg /kg (max 150 mg) intravenously over 10 minutes.

Also known as: APOCARD

Flecainide

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients ≥ 20 and ≤65 year-olds.
• Patients with paroxysmal AF lasting \<48 hours, in whom pharmacological cardioversion may be indicated.
• Hemodynamically stable patients (systolic blood pressure \> 100 mm Hg and \< 160 mm Hg. Diastolic blood pressure \<95 mm Hg).
• Weight of 45-136 kg .
• Appropriate anticoagulation therapy according to the clinical practice guidelines of the European Society of Cardiology in paroxysmal AF episodes lasting \< 48 hours.
• Signed informed consent.

You may not qualify if:

• Corrected QT interval\> 440 milliseconds, long QT family or history of 'Torsades de Pointes' syndrome.
• Symptomatic bradycardia or ventricular rate \<50 bpm without a pacemaker, or QRS interval\> 140 milliseconds.
• Patients with heart failure regardless of the classification of the New York Heart Association (NYHA).
• Second or third degree atrioventricular block, or right bundle branch block associated with partial left bundle branch block (bifascicular block).
• Valvular stenosis, hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy, or constrictive pericarditis.
• Previous unsuccessful electrical cardioversion or longstanding atrial fibrillation (no attempt to convert to sinus rhythm).
• Treatment with other investigational drug within 60 days before enrollment.
• Previous treatment with vernakalant.
• Secondary causes of atrial fibrillation, hyperthyroidism, uncorrected electrolyte imbalance, or digoxin toxicity.
• IV / oral treatment with Class I or III antiarrhythmics (except amiodarone) in the previous 48 hours.
• Renal failure with glomerular filtration rate \<35 ml / min.
• Intravenous / oral amiodarone within the previous 3 months.
• Pregnant or nursing women.
• Intolerance or allergy to any of the two drugs being studied.
• Refusal to sign the informed consent.

Sponsors & Collaborators

• David Filgueiras-Rama: lead
• Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III: collaborator

Study Sites (1)

Hospital Clínico Universitario San Carlos

Madrid, Madrid/Madrid, 28040, Spain

Location

Related Publications (23)

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MeSH Terms

Conditions

Atrial Fibrillation

Interventions

vernakalant; Flecainide

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Nicasio Pérez-Castellano, MD, PhD

  Hospital San Carlos, Madrid

  STUDY CHAIR

• Asunción Conde, PharmD

  Hospital San Carlos, Madrid

  STUDY CHAIR

• María-Jesús García-Torrent, PharmD, PhD

  Hospital San Carlos, Madrid

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD PhD

Study Record Dates

• First Submitted: December 5, 2016
• First Posted: December 29, 2016
• Study Start: January 1, 2017
• Primary Completion: June 1, 2023
• Study Completion: August 1, 2023
• Last Updated: August 7, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)