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

SELECTI-CARFAP

* 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.

2017-01-01

2023-06-01

2023-08-01

Completed

Early phase I

50

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.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE4'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 50, 'type': 'ACTUAL'}}

2023-08-07