Comparison of Effectiveness of Ranolazine Plus Metoprolol Combination vs. FlecainidE pluS Metoprolol Combination in ATrial Fibrillation Recurrences FOllowing PhaRmacological or Electrical CardioverSion of AtRial Fibrillation

NCT03162120 | Withdrawn Phase 2

• 1 other identifier: IIS-EL-VASS-2017
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice with a prevalence reaching 5% in patients older than 65 years and an incidence that increases progressively with age.1 According to the most recent guidelines, class Ic anti-arrhythmic drugs are considered the first line treatment in patients without significant structural heart disease. Flecainide is effective in preventing AF recurrences in 31-61% of cases according to different studies.2-5 A recent study showed that the combination of Flecainide and Metoprolol improves effective rhythm control in patients with persistent symptomatic AF compared to Flecainide or Metoprolol alone.6 In contrast, the combination of Flecainide and Metoprolol conferred no significant benefit over Flecainide alone in patients with paroxysmal AF. This suggests different underlying mechanisms for paroxysmal and persistent AF. Pulmonary veins are likely the main focus triggering paroxysmal AF while in persistent AF the role of pulmonary veins is less important.

Conditions

Atrial Fibrillation; Recurrence

Outcome Measures

Primary Outcomes (1)

• Number of 1-year-recurrences

  efficacy and safety of the combination of RN and Metoprolol vs. the combination of Flecainide and Metoprolol in preventing AF recurrences during a 1-year follow-up period in patients with AF of longer than 24-hour duration who were cardioverted to sinus rhythm either pharmacologically or electrically

  12 months

Secondary Outcomes (1)

• Number of 48-hours-recurrences

  48 hours

Study Arms (2)

Ranolazine plus Metoprolol Combination

ACTIVE COMPARATOR

Ranolazine plus Metoprolol Combination in ATrial Fibrillation Recurrences FOllowing PhaRmacological or Electrical CardioverSion of AtRial Fibrillation

Drug: Ranolazine plus Metoprolol Combination

FlecainidE pluS Metoprolol Combination

ACTIVE COMPARATOR

FlecainidE pluS Metoprolol Combination in in ATrial Fibrillation Recurrences FOllowing PhaRmacological or Electrical CardioverSion of AtRial Fibrillation

Drug: FlecainidE pluS Metoprolol Combination

Interventions

Ranolazine plus Metoprolol Combination DRUG

Ranolazine plus Metoprolol Combination in ATrial Fibrillation Recurrences FOllowing PhaRmacological or Electrical CardioverSion of AtRial Fibrillation

Also known as: RM group

Ranolazine plus Metoprolol Combination

FlecainidE pluS Metoprolol Combination DRUG

FlecainidE pluS Metoprolol Combination in ATrial Fibrillation Recurrences FOllowing PhaRmacological or Electrical CardioverSion of AtRial Fibrillation

Also known as: FM group

FlecainidE pluS Metoprolol Combination

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients with AF
• recently converted to sinus rhythm (\>24hrs and \< 7 days)
• admitted in the 3rd University Cardiology Clinic of Ippokrateion Hospital
• eligible to participate in the study and follow the study procedures
• signed informed consent

You may not qualify if:

• use of IC antiarrhythmic agents or
• Sotalol during the last 48 hours,
• chronic use of oral or intravenous Amiodarone for the last 48 hours,
• recent acute coronary syndrome,
• heart failure New York Heart Association class III or IV,
• severe left ventricular dysfunction with left ventricular ejection fraction \<40%,
• atrioventricular conduction disorders (atrioventricular block,
• complete left bundle branch block and bi-fascicular block),
• heart rate \< 50 bpm,
• sick sinus syndrome,
• thyroid dysfunction and severe pulmonary, renal, or
• liver disease
• \- not eligible to participate in the study and follow the study procedures
• no signed informed consent

Sponsors & Collaborators

• Elpen Pharmaceutical Co. Inc.: lead

Related Publications (17)

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  PMID: 11602543 BACKGROUND

• Aliot E, Capucci A, Crijns HJ, Goette A, Tamargo J. Twenty-five years in the making: flecainide is safe and effective for the management of atrial fibrillation. Europace. 2011 Feb;13(2):161-73. doi: 10.1093/europace/euq382. Epub 2010 Dec 7.

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• Anderson JL, Gilbert EM, Alpert BL, Henthorn RW, Waldo AL, Bhandari AK, Hawkinson RW, Pritchett EL. Prevention of symptomatic recurrences of paroxysmal atrial fibrillation in patients initially tolerating antiarrhythmic therapy. A multicenter, double-blind, crossover study of flecainide and placebo with transtelephonic monitoring. Flecainide Supraventricular Tachycardia Study Group. Circulation. 1989 Dec;80(6):1557-70. doi: 10.1161/01.cir.80.6.1557.

  PMID: 2513143 BACKGROUND

• Naccarelli GV, Dorian P, Hohnloser SH, Coumel P. Prospective comparison of flecainide versus quinidine for the treatment of paroxysmal atrial fibrillation/flutter. The Flecainide Multicenter Atrial Fibrillation Study Group. Am J Cardiol. 1996 Jan 25;77(3):53A-59A. doi: 10.1016/s0002-9149(97)89118-7.

  PMID: 8607392 BACKGROUND

• van Wijk LM, den Heijer P, Crijns HJ, van Gilst WH, Lie KI. Flecainide versus quinidine in the prevention of paroxysms of atrial fibrillation. J Cardiovasc Pharmacol. 1989 Jan;13(1):32-6. doi: 10.1097/00005344-198901000-00005.

  PMID: 2468933 BACKGROUND

• Capucci A, Piangerelli L, Ricciotti J, Gabrielli D, Guerra F. Flecainide-metoprolol combination reduces atrial fibrillation clinical recurrences and improves tolerability at 1-year follow-up in persistent symptomatic atrial fibrillation. Europace. 2016 Nov;18(11):1698-1704. doi: 10.1093/europace/euv462. Epub 2016 Feb 17.

  PMID: 26893497 BACKGROUND

• Fragakis N, Koskinas KC, Vassilikos V. Ranolazine as a promising treatment option for atrial fibrillation: electrophysiologic mechanisms, experimental evidence, and clinical implications. Pacing Clin Electrophysiol. 2014 Oct;37(10):1412-20. doi: 10.1111/pace.12486. Epub 2014 Aug 19.

  PMID: 25138058 BACKGROUND

• Sicouri S, Glass A, Belardinelli L, Antzelevitch C. Antiarrhythmic effects of ranolazine in canine pulmonary vein sleeve preparations. Heart Rhythm. 2008 Jul;5(7):1019-26. doi: 10.1016/j.hrthm.2008.03.018. Epub 2008 Mar 21.

  PMID: 18598958 BACKGROUND

• Burashnikov A, Di Diego JM, Zygmunt AC, Belardinelli L, Antzelevitch C. Atrium-selective sodium channel block as a strategy for suppression of atrial fibrillation: differences in sodium channel inactivation between atria and ventricles and the role of ranolazine. Circulation. 2007 Sep 25;116(13):1449-57. doi: 10.1161/CIRCULATIONAHA.107.704890. Epub 2007 Sep 4.

  PMID: 17785620 BACKGROUND

• Murdock DK, Reiffel JA, Kaliebe J, Larrain G. The Conversion of Paroxysmal or Initial Onset Atrial Fibrillation with Oral Ranolazine: Implications for a New

  BACKGROUND

• Fragakis N, Koskinas KC, Katritsis DG, Pagourelias ED, Zografos T, Geleris P. Comparison of effectiveness of ranolazine plus amiodarone versus amiodarone alone for conversion of recent-onset atrial fibrillation. Am J Cardiol. 2012 Sep 1;110(5):673-7. doi: 10.1016/j.amjcard.2012.04.044. Epub 2012 May 22.

  PMID: 22621799 BACKGROUND

• Koskinas KC, Fragakis N, Katritsis D, Skeberis V, Vassilikos V. Ranolazine enhances the efficacy of amiodarone for conversion of recent-onset atrial fibrillation. Europace. 2014 Jul;16(7):973-9. doi: 10.1093/europace/eut407. Epub 2014 Jan 27.

  PMID: 24473502 BACKGROUND

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• Schubert B, Vandongen AM, Kirsch GE, Brown AM. Inhibition of cardiac Na+ currents by isoproterenol. Am J Physiol. 1990 Apr;258(4 Pt 2):H977-82. doi: 10.1152/ajpheart.1990.258.4.H977.

  PMID: 2158748 BACKGROUND

• Burashnikov A, Sicouri S, Di Diego JM, Belardinelli L, Antzelevitch C. Synergistic effect of the combination of ranolazine and dronedarone to suppress atrial fibrillation. J Am Coll Cardiol. 2010 Oct 5;56(15):1216-24. doi: 10.1016/j.jacc.2010.08.600.

  PMID: 20883928 BACKGROUND

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  PMID: 19952329 BACKGROUND

MeSH Terms

Conditions

Atrial Fibrillation; Recurrence

Interventions

Ranolazine; Flecainide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperidines

Study Officials

• Vasilios Vasilikos, MD

  3rd University Cardiology Clinic of Ippokrateion Hospital, Thessaloniki, Greece

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2017
• First Posted: May 22, 2017
• Study Start: September 1, 2018
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: May 13, 2019

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share