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

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

Interventions

DRUG

Vernakalant

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.

DRUG

Flecainide

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

Sponsors & Collaborators

• Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III

  collaborator OTHER

• David Filgueiras-Rama

  lead OTHER

Principal Investigators

• Nicasio Pérez-Castellano, MD, PhD · Hospital San Carlos, Madrid

• Asunción Conde, PharmD · Hospital San Carlos, Madrid

• María-Jesús García-Torrent, PharmD, PhD · Hospital San Carlos, Madrid

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

20 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-01-31

Primary Completion

2023-06-30

Completion

2023-08-31

Countries

• Spain

Study Locations