Kansai Plus Atrial Fibrillation Trial
Condition: Atrial Fibrillation
MeSH terms: Atrial Fibrillation
Study type: Interventional
Phase: Phase 4

Summary: 
      This is a 2x2 factorial randomized controlled trial (KPAF Trial), evaluating two different
      pharmacological approaches to improve long-term outcome of catheter ablation for atrial
      fibrillation (AF). The study is composed of UNmasking Dormant Electrical Reconduction by
      Adenosine TriPhosphate (UNDER-ATP) Trial and Efficacy of Antiarrhythmic Drugs Short-Term Use
      after Catheter Ablation for Atrial Fibrillation (EAST-AF) Trial. Patients with paroxysmal or
      persistent AF will be randomized to ATP guide ablation or control group in a 1:1 ratio before
      the procedure (UNDER-ATP Trial). Excluding those with severe procedural complications or
      substantial bradycardia identified first after ablation for persistent AF, patients will be
      randomized in a 1:1 ratio to antiarrhythmic-drug (AAD) or control group after the procedure
      (EAST-AF Trial).
    

Detailed description: 
      Atrial fibrillation (AF) is a common tachyarrhythmia causing disabling symptoms and stroke.
      Although catheter ablation has been developed as curative therapy for AF, it is still
      associated with considerably high rate of AF recurrence, approximately 30-40% in patients
      with paroxysmal AF and 50-80% among those with persistent AF.

      Because most ectopic beats triggering AF originate from myocardial sleeves in pulmonary veins
      (PVs), the mainstay of catheter ablation for AF is PV isolation. The major cause of early and
      late AF recurrence following successful PV isolation is considered to be electrical
      reconnection between left atrium (LA) and PVs. Therefore, it is important to establish
      permanent LA-PV disconnection, although high energy application is associated with increased
      risk of procedural complications, including cardiac tamponade, PV stenosis/occlusion and
      LA-esophageal fistula.

      Adenosine or adenosine triphosphate (ATP) has been reported to unmask dormant electrical
      conduction between LA and PVs after successful PV isolation. Thus, adenosine or ATP guide
      additional ablation until disappearance of dormant electrical conduction has been proposed as
      adjunctive approach to establish permanent LA-PV disconnection and thereby decrease AF
      recurrence post ablation. However, only several small observational studies showed the
      efficacy of adenosine or ATP guide ablation, and this approach is not recognized as standard
      therapy.

      On the other hand, sizable portion of AF recurrence early after ablation is considered to be
      due to irritability in LA from the ablation. Thus, short term use of antiarrhythmic drugs
      (AADs) after ablation has been proposed as adjunctive approach not only to prevent early AF
      recurrence, but also to improve long-term outcome by promoting reverse remodeling of LA
      through maintenance of sinus rhythm during the first 2-3 months period after ablation.

      The 5A study, a recently reported single-center study, randomized 110 patients with
      paroxysmal AF to AAD or control group. In the AAD group, AAD was used for 6 weeks after
      ablation. Although AAD significantly reduced early AF recurrence during the first 6 weeks,
      discontinuation of the drug resulted in similar AF-free rates at 6 months. Considering the
      small number of patients enrolled in the 5A study, the results were not conclusive, lacking
      statistical power to determine the effect of short-tem use of AAD following successful
      ablation for AF on long-term clinical outcome. Also, this approach is expected to be more
      effective in patients with persistent AF rather than those with 'self-terminating' paroxysmal
      AF. In addition, 6 weeks may have been too short to promote reverse remodeling of LA.

      Accordingly, we planned a 2x2 factorial randomized controlled trial (KPAF trial), evaluating
      the efficacy of ATP guide additional ablation and 90 days use of AADs post ablation.
      Approximately 2,000 patients with paroxysmal or persistent AF will be randomized to ATP guide
      ablation or control group in a 1:1 ratio before the procedure (UNDER-ATP trial). Excluding
      those with severe procedural complications or those with substantial bradycardia identified
      first after ablation for persistent AF, patients will be randomized in a 1:1 ratio to AAD or
      control group after the procedure (EAST-AF trial). Approximately 5% of the patients are
      expected to be excluded from the EAST-AF trial after ablation, but those patients will not be
      excluded from the UNDER-ATP trial, whose data will be analyzed by intention-to-treat manner.
      The follow-up duration is one year.
    

Intervention name(s): ATP guide additional ablation.; Antiarrhythmic drug (AAD); ATP guide additional ablation.; Control; Control; Antiarrhythmic drug (AAD); Control; Control
Intervention type(s): Procedure; Drug; Procedure; Drug; Procedure; Drug; Procedure; Drug
Intervention description(s): Following successful PV isolation, intravenous ATP of 0.4 mg/body-weight-kg is rapidly is injected, and dormant LA-PV conduction is evaluated. If dormant LA-PV conduction is unmasked, then additional radiofrequency energy applications are delivered to the conduction gaps until disappearance of dormant LA-PV conduction.; Following successful ablation, AAD (Vaughan Williams class I or III) is administered for 90 days. The recommended drugs are flecainide, propafenone, sotalol and amiodarone, but the final choice of drug and dosage is left to the discretion of the attending physician.; Following successful PV isolation, intravenous ATP of 0.4 mg/body-weight-kg is rapidly is injected, and dormant LA-PV conduction is evaluated. If dormant LA-PV conduction is unmasked, then additional radiofrequency energy applications are delivered to the conduction gaps until disappearance of dormant LA-PV conduction.; Following successful ablation, AAD (Vaughan Williams class I or III) including flecainide, propafenone, sotalol and amiodarone is not used during the period of 0 - 90 days.; Following successful PV isolation, intravenous ATP is not administered.; Following successful ablation, AAD (Vaughan Williams class I or III) is administered for 90 days. The recommended drugs are flecainide, propafenone, sotalol and amiodarone, but the final choice of drug and dosage is left to the discretion of the attending physician.; Following successful PV isolation, intravenous ATP is not administered.; Following successful ablation, AAD (Vaughan Williams class I or III) including flecainide, propafenone, sotalol and amiodarone is not used during the period of 0 - 90 days.
Other intervention name(s): The brand names of ATP; Adetphos-L, Trinosin-S; Brand names; Tambocor, Pronon, Sotacor, Ancaron; The brand names of ATP; Adetphos-L, Trinosin-S; Brand names; Tambocor, Pronon, Sotacor, Ancaron; The brand names of ATP; Adetphos-L, Trinosin-S; Brand names; Tambocor, Pronon, Sotacor, Ancaron; The brand names of ATP; Adetphos-L, Trinosin-S; Brand names; Tambocor, Pronon, Sotacor, Ancaron
Intervention MeSH terms: Anti-Arrhythmia Agents; Flecainide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: atrial fibrillation; catheter ablation; adenosine triphosphate; antiarrhythmic drugs