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Efficacy of Pilsicainide After Radiofrequency Ablation of Paroxysmal Atrial Fibrillation

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ClinicalTrials.gov Identifier: NCT01775891
Recruitment Status : Unknown
Verified February 2013 by Young-Hoon Kim, Korea University.
Recruitment status was:  Recruiting
First Posted : January 25, 2013
Last Update Posted : February 26, 2013
Sponsor:
Information provided by (Responsible Party):
Young-Hoon Kim, Korea University

Brief Summary:
Investigators hypothesized that the use of Pilsicainide after radiofrequency ablation of AF could reduce the incidence of recurrence of atrial arrhythmia during follow up compared with other class IC antiarrhythmic drugs.

Condition or disease Intervention/treatment Phase
Paroxysmal Atrial Fibrillation Drug: pilsicainide Drug: other class IC antiarrhythmic drug Not Applicable

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Detailed Description:

Catheter ablation has become an integral part of the management of atrial fibrillation (AF), when a strategy to preserve normal sinus rhythm is required. However, recurrence of atrial arrhythmias is common after AF ablation. In order to prevent these arrhythmia recurrences, antiarrhythmic drugs (AADs) are often resumed empirically after AF ablation. Previously a prospective randomized trial demonstrated that the treatment with AADs during the first 6-weeks after AF ablation reduced the incidence of clinically significant atrial arrhythmias and need for cardioversion or hospitalization for arrhythmia management.

Pilsicainide is a class IC antiarrhythmic drug originally developed in Japan, which has a pure sodium channel blocking action with slow recovery pharmacokinetics. Its mechanism of action appears to provide new insight into the pharmacological conversion of AF.

In experimental studies, pilsicainide has a potent depressant effect on intra-atrial conduction and a prolonging effect on the atrial effective refractory period (ERP). Theoretically the suppression of conduction velocity minimizes the prolongation of wavelength induced by the increase in the ERP and may thus serve to allow the continuation of multiple re-entrant wavelets. Iwasa et al demonstrated that pilsicainide was more effective at terminating vagally induced AF than propafenone, despite the greater effect of propafenone on wavelength, suggesting that suppression of conduction velocity may play an important role in terminating AF. Moreover, Wijffels et al reported that the pharmacological cardioversion of AF cannot be explained by the prolongation of wavelength.

The effects of a single oral treatment of pilsicainide were compared with that of a disopyramide infusion in a multicentre trial. Seventy two patients with symptomatic paroxysmal AF were randomised to receive either a single oral dose of pilsicainide (100-150mg) or an infusion of disopyramide (2 mg/kg; maximum dose = 100mg). In the pilsicainide group, the cumulative percentage of conversion to sinus rhythm within 120 minutes was high as disopyramide (73% vs 56%). Moreover, the conversion time of pilsicainide is shorter than that of other class IC antiarrhythmics, including flecainide and propafenone, in patients with recent-onset AF. This seems likely to be due to the favorable pharmacokinetics of pilsicainide, including its rapid absorption from the gastrointestinal tract, the absence of changes from a first-pass effect, and a short elimination half-life.

In the case of an unsuccessful ablation for AF, AADs that were ineffective before the ablation are sometimes effective. The effects and mechanisms of hybrid therapy with pilsicainide and PV isolation for AF have been assessed. Seventy four patients with paroxysmal AF in whom pilsicainide was ineffective underwent PV isolation. A second PV isolation was performed in 31 patients among 42 recurred patients (57%). Pilsicainide was re-administered in recurred patients even after the second session. Amng 21 patients with recurrence of AF, pilsicainide and eliminated AF in 11 patients (success with hybrid therapy was 86%).

In patients with paroxysmal AF, pilsicainide significantly prolonged the ERP of the distal pulmonary vein (PV), PV-left atrium (LA) junction and LA, and the conduction time from the distal PV to the PV-LA junction. In some patients, PV-LA conduction block has been observed just before pilsicainide-induced termination of AF; this isolation of the PV may provide a new insight into the mechanism of pharmacological conversion of AF. Hybrid therapy with pilsicainide and PV isolation (by radiofrequency catheter ablation) appears to be an effective therapeutic approach for AF. The pharmacological PV isolation by pilsicainide and its suppression of focal discharges from atrial tissue may prevent the development of AF after unsuccessful ablation. These mechanism makes it suitable for hybrid therapy with catheter ablation of the PVs.

Therefore investigators hypothesized that the use of Pilsicainide after radiofrequency ablation of AF could reduce the incidence of recurrence of atrial arrhythmia during follow up compared with other AADs. Furthermore, we seek to identify whether there are clinical predictors of AF recurrence at 1-year follow-up and the relationship of early recurrence during blanking period and recurrence during 1-year follow up.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 245 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy of Pilsicainide After Radiofrequency Ablation of Paroxysmal Atrial Fibrillation Compared With Other Class IC Anti-arrhythmic Drugs
Study Start Date : July 2012
Estimated Primary Completion Date : July 2015
Estimated Study Completion Date : July 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: pilsicainide
The dose of pilsicainide will be 50mg tid PO. Pilsicainide will be started on the night of the ablation for a duration of at least 3 months. Physicians were encouraged to stop the drugs following the 3 months treatment if possible.
Drug: pilsicainide
The dose of pilsicainide will be 50mg tid PO. Pilsicainide will be started on the night of the ablation for a duration of at least 3 months. Physicians were encouraged to stop the drugs following the 3 months treatment if possible.
Other Name: Pilsicainide (Sunrhythm®) Daiichi Sankyo

Drug: other class IC antiarrhythmic drug
Other class IC antiarrhythmic drug that they had been taking before catheter ablation will be administrated.(flecainide 100mg bid PO or propafenone 225mg tid) Antiarrhythmic drug will be started on the night of the ablation for a duration of at least 3 months. Physicians were encouraged to stop the drugs following the 3 months treatment if possible.
Other Name: flecainide 100mg bid PO or propafenone 225mg tid

Placebo Comparator: other class IC antiarrhythmic drug
Other class IC antiarrhythmic drug that they had been taking before catheter ablation will be administrated.(flecainide 100mg bid PO or propafenone 225mg tid) Antiarrhythmic drug will be started on the night of the ablation for a duration of at least 3 months. Physicians were encouraged to stop the drugs following the 3 months treatment if possible.
Drug: pilsicainide
The dose of pilsicainide will be 50mg tid PO. Pilsicainide will be started on the night of the ablation for a duration of at least 3 months. Physicians were encouraged to stop the drugs following the 3 months treatment if possible.
Other Name: Pilsicainide (Sunrhythm®) Daiichi Sankyo

Drug: other class IC antiarrhythmic drug
Other class IC antiarrhythmic drug that they had been taking before catheter ablation will be administrated.(flecainide 100mg bid PO or propafenone 225mg tid) Antiarrhythmic drug will be started on the night of the ablation for a duration of at least 3 months. Physicians were encouraged to stop the drugs following the 3 months treatment if possible.
Other Name: flecainide 100mg bid PO or propafenone 225mg tid




Primary Outcome Measures :
  1. freedom from recurrence of any atrial arrhythmia within 1 year [ Time Frame: 1 year ]


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • patients with drug-refractory paroxysmal atrial fibrillation who requires catheter ablation
  • patients who are aged 18-80 and agree with this study

Exclusion Criteria:

  • patients who do not agree with this study
  • patients with a history of catheter ablatio or surgery for atrial fibrillation
  • patients who experienced side effects of pilsicainide before
  • patients who has galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
  • patients who has congestive heart failure with ejection fraction<40% or decompensated heart failure
  • patients with significant coronary artery disease, liver/renal disease
  • patients who has other kinds of arrhythmic which requires active treatment
  • contraindication to warfarin therapy
  • life expectancy <1 year]
  • pregnancy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01775891


Contacts
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Contact: Young-Hoon Kim, M.D., PhD. +82-10-9370-3337 ypruimin@naver.com
Contact: Yae Min Park, M.D. +82-10-9370-3337 ypruimin@naver.com

Locations
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Korea, Republic of
Arrhythmia center, Anam Hospital, Korea University Recruiting
Seoul, Korea, Republic of, 136-705
Contact: Young-Hoon Kim, M.D. PhD.    +82-10-9370-3337    ypruimin@naver.com   
Contact: Yae Min Park, M.D.    +82-10-9370-3337    ypruimin@naver.com   
Sponsors and Collaborators
Korea University
Investigators
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Principal Investigator: Young-Hoon Kim, MD., PhD Arrhythmia center, Anam hospital, Korea university

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Responsible Party: Young-Hoon Kim, M.D. PhD, Korea University
ClinicalTrials.gov Identifier: NCT01775891     History of Changes
Other Study ID Numbers: PIL245
First Posted: January 25, 2013    Key Record Dates
Last Update Posted: February 26, 2013
Last Verified: February 2013
Keywords provided by Young-Hoon Kim, Korea University:
pilsicainide
class IC antiarrhythmic drug
paroxysmal atrial fibrillation
catheter ablation
Additional relevant MeSH terms:
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Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Flecainide
Propafenone
Pilsicainide
Lidocaine
Anti-Arrhythmia Agents
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents