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Kansai Plus Atrial Fibrillation Trial (KPAF)

K

Kyoto University, Graduate School of Medicine

Status and phase

Completed
Phase 4

Conditions

Atrial Fibrillation

Treatments

Procedure: ATP guide additional ablation.
Drug: Antiarrhythmic drug (AAD)
Drug: Control

Study type

Interventional

Funder types

Other

Identifiers

NCT01477983
KPAFKUHP

Details and patient eligibility

About

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).

Full 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.

Enrollment

2,113 patients

Sex

All

Ages

21 to 79 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  • Patients undergoing first catheter ablation including PV isolation for paroxysmal or persistent atrial fibrillation
  • Patients who are 21-79 years old
  • Able to be followed for one year in an out-patient clinic
  • Willing to sign the consent form for participation

Exclusion criteria

  • Contraindication or intolerance to adenosine triphosphate or Vaughan Williams class I or III antiarrhythmic drugs, including severe bronchial asthma, severe vasospastic angina, and substantial bradycardia including sinus node dysfunction with prolonged pauses on termination of atrial fibrillation
  • Age =< 20 years or => 80 years
  • Renal insufficiency (serum creatinine >=2.0mg/dl or hemodialysis)
  • NYHA class IV heart failure
  • Left ventricular ejection fraction < 40%
  • Left atrial diameter > 55mm
  • Very long-lasting (>=5years) persistent atrial fibrillation
  • Ineligible for optimal anticoagulant therapy
  • History of myocardial infarction within the past 6 months
  • Prior or planned open heart surgery
  • Severe valve heart disease
  • Unable to be followed in an out-patient clinic for one year
  • Unwilling to sign the consent form for participation
  • When the attending physician are unwilling to enroll the patient in the study
  • When the attending physician consider inappropriate to enroll the patient in the study
  • Those with severe procedural complications (EAST-AF trial only)

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

2,113 participants in 4 patient groups

ATP guide additional ablation - AAD
Active Comparator group
Description:
UNDER-ATP trial: ATP guide additional ablation, EAST-AF trial: AAD for 90 days
Treatment:
Procedure: ATP guide additional ablation.
Procedure: ATP guide additional ablation.
Drug: Antiarrhythmic drug (AAD)
Drug: Antiarrhythmic drug (AAD)
Control - AAD
Active Comparator group
Description:
UNDER-ATP trial: Control, EAST-AF trial: AAD for 90 days
Treatment:
Drug: Antiarrhythmic drug (AAD)
Drug: Antiarrhythmic drug (AAD)
ATP guide additinal ablation - Control
Active Comparator group
Description:
UNDER-ATP trial: ATP guide additional ablation, EAST-AF trial: Control
Treatment:
Drug: Control
Drug: Control
Drug: Control
Procedure: ATP guide additional ablation.
Procedure: ATP guide additional ablation.
Drug: Control
Control - Control
Active Comparator group
Description:
UNDER-ATP trial: Control, EAST-AF trial: Control
Treatment:
Drug: Control
Drug: Control
Drug: Control
Drug: Control

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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