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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

Tracking Information
First Submitted Date  ICMJE January 23, 2013
First Posted Date  ICMJE January 25, 2013
Last Update Posted Date February 26, 2013
Study Start Date  ICMJE July 2012
Estimated Primary Completion Date July 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 24, 2013)
freedom from recurrence of any atrial arrhythmia within 1 year [ Time Frame: 1 year ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01775891 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy of Pilsicainide After Radiofrequency Ablation of Paroxysmal Atrial Fibrillation
Official Title  ICMJE Efficacy of Pilsicainide After Radiofrequency Ablation of Paroxysmal Atrial Fibrillation Compared With Other Class IC Anti-arrhythmic Drugs
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Paroxysmal Atrial Fibrillation
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: pilsicainide
    • Drug: other class IC antiarrhythmic drug
  • 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.
    Interventions:
    • Drug: pilsicainide
    • Drug: other class IC antiarrhythmic drug
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: January 24, 2013)
245
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2015
Estimated Primary Completion Date July 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Korea, Republic of
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01775891
Other Study ID Numbers  ICMJE PIL245
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Young-Hoon Kim, Korea University
Study Sponsor  ICMJE Korea University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Young-Hoon Kim, MD., PhD Arrhythmia center, Anam hospital, Korea university
PRS Account Korea University
Verification Date February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP