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

August 4, 2023 updated by: David Filgueiras-Rama

Randomized Clinical Trial to Study Pharmacological Cardioversion of Paroxysmal Atrial Fibrillation by Vernakalant and Flecainide

  • 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

  • Background: Different research strategies aim at understanding the mechanisms underlying the maintenance of atrial fibrillation (AF), while preventing ventricular pro-arrhythmia related to the use of anti-arrhythmic drugs to restore sinus rhythm. Such aims might be achieved by drugs that effectively terminate reentrant sources identified during AF, along with an atrial specific and atria-preferential blockade of ionic currents. The latter may be especially relevant in paroxysmal AF episodes with fast atrial activation rates, in which INa and IK,ACh are involved in the maintenance of fast atrial reentrant sources underlying AF.
  • Objective: 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 AF.
  • The hypothesis is that a drug blocking atrial specific and atria-preferential dynamics of ionic currents (IK,ACh and INa, 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.
  • Design: 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 for 90 minutes upon drug administration to acquire both 12-lead digitized ECG signals and non-invasive body surface potential mapping. Body surface recordings and conventional ECG signals will be exported to obtain temporal and spectral parameters of atrial activity during AF, and measure organization and atrial rate in both groups of patients undergoing pharmacological cardioversion. The success rate of cardioversion obtained in both groups will be correlated with the patterns of activation and spectral parameters obtained from the body surface, which will provide what type of paroxysmal AF episodes are suitable to terminate upon administration of anti-arrhythmic drugs with an atrial specific and atria-preferential profile.

Electrical cardioversion will be performed in subjects with unsuccessful pharmacological cardioversion within the first 24 h. after vernakalant or flecainide administration.

The results obtained in the clinical setting will be studied in realistic mathematical models to further understand the capability of both drugs to terminate paroxysmal AF.

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 4

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

Study Contact Backup

Study Locations

  • Spain
    • Madrid/Madrid
      • Madrid, Madrid/Madrid, Spain, 28040
        • Hospital Clínico Universitario San Carlos

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

20 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

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

Exclusion Criteria:

  1. Corrected QT interval> 440 milliseconds, long QT family or history of 'Torsades de Pointes' syndrome.
  2. Symptomatic bradycardia or ventricular rate <50 bpm without a pacemaker, or QRS interval> 140 milliseconds.
  3. Patients with heart failure regardless of the classification of the New York Heart Association (NYHA).
  4. Second or third degree atrioventricular block, or right bundle branch block associated with partial left bundle branch block (bifascicular block).
  5. Cardiogenic or septic shock, chronic myocardial infarction, acute coronary syndrome, or heart surgery in the previous 30 days before inclusion.
  6. Valvular stenosis, hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy, or constrictive pericarditis.
  7. Previous unsuccessful electrical cardioversion or longstanding atrial fibrillation (no attempt to convert to sinus rhythm).
  8. Treatment with other investigational drug within 60 days before enrollment.
  9. Previous treatment with vernakalant.
  10. Secondary causes of atrial fibrillation, hyperthyroidism, uncorrected electrolyte imbalance, or digoxin toxicity.
  11. IV / oral treatment with Class I or III antiarrhythmics (except amiodarone) in the previous 48 hours.
  12. Renal failure with glomerular filtration rate <35 ml / min.
  13. Intravenous / oral amiodarone within the previous 3 months.
  14. Pregnant or nursing women.
  15. Intolerance or allergy to any of the two drugs being studied.
  16. Refusal to sign the informed consent.

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: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Flecainide
Conventional cardioversion group using intravenous flecainide.
Drug: Flecainide
2 mg /kg (max 150 mg) intravenously over 10 minutes.
Other Names:
  • APOCARD
Active Comparator: Vernakalant
Atria-preferential and atrial-specific blockade group using intravenous vernakalant.
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.
Other Names:
  • BRINAVESS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Electrocardiographic-based spectral parameters of atrial fibrillatory activity (Dominant frequency) associated with successful or unsuccessful cardioversion in both groups of patients.
Time Frame: 18 months

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cardioversion success (yes/no) in patients with paroxysmal atrial fibrillation episodes lasting < 24 hours or ≥24 hours.
Time Frame: 18 months
The investigators will quantify the difference in cardioversion success (yes/no) between 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.
Time Frame: 18 months
The investigators will quantify the difference in baseline dominant frequency values (Hz) of atrial fibrillatory activity between 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.
Time Frame: 24 months

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.
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.
Time Frame: 24 months
The investigators will quantify dominant frequency changes (Hz) and rotor meandering (mm) under the effect of vernakalant or flecainide in 2D computational models.
24 months
Atrial Fibrillation Quality of Life questionnaire (AF-QOL).
Time Frame: 24 months
The Investigators will quantify the effects of atrial fibrillation on patients´ quality of life base on of the Atrial Fibrillation Quality of Life questionnaire (AF-QOL).
24 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patient's perception during cardioversion. The investigators will used a custom-designed five-question questionnaire as follows:
Time Frame: 24 months

i) Do you recall something from the cardioversion attempt? yes/no. ii) If (1) is yes, was it uncomfortable? yes/no. iii) Did you feel any pain during the cardioversion attempt? yes/no. iv) Please, provide an score from '0' to '10' to evaluate your general perception of the cardioversion attempt.

v) If necessary, would you undergo another cardioversion attempt using the same strategy? yes/no.
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

David Filgueiras-Rama

Collaborators

Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III

Investigators

  • Study Chair: 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

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

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 (Actual)

January 1, 2017

Primary Completion (Actual)

June 1, 2023

Study Completion (Actual)

August 1, 2023

Study Registration Dates

First Submitted

December 5, 2016

First Submitted That Met QC Criteria

December 23, 2016

First Posted (Estimated)

December 29, 2016

Study Record Updates

Last Update Posted (Actual)

August 7, 2023

Last Update Submitted That Met QC Criteria

August 4, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SELECTI-CARFAP

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

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.

Clinical Trials on Paroxysmal Atrial Fibrillation

Clinical Trials on Flecainide

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Peru

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe