Kansai Plus Atrial Fibrillation Trial
Information source: Kyoto University, Graduate School of Medicine
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Atrial Fibrillation
Intervention: ATP guide additional ablation. (Procedure); Antiarrhythmic drug (AAD) (Drug); ATP guide additional ablation. (Procedure); Control (Drug); Control (Procedure); Antiarrhythmic drug (AAD) (Drug); Control (Procedure); Control (Drug)
Phase: Phase 4
Status: Active, not recruiting
Sponsored by: Kyoto University, Graduate School of Medicine Official(s) and/or principal investigator(s): Satoshi Shizuta, MD, Principal Investigator, Affiliation: Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine
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).
Clinical Details
Official title: Kansai Plus Atrial Fibrillation Trial; UNmasking Dormant Electrical Reconduction by Adenosine TriPhosphate Trial; Efficacy of Antiarrhythmic Drugs Short-Term Use After Catheter Ablation for Atrial Fibrillation Trial
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Atrial tachyarrhythmias lasting for > 30 seconds or requiring repeat ablation, hospital admission, cardioversion or antiarrhythmic drug (AAD) therapy between 91 and 365 days after ablation. (Both trials)
Secondary outcome: Repeat Ablation for atrial tachyarrhythmias. (Both trials)Atrial tachyarrhythmias lasting for > 30 seconds or requiring repeat ablation, hospital admission, cardioversion or antiarrhythmic drug (AAD) therapy* between 0 and 90 days after ablation. (Both trials) Atrial tachyarrhythmias lasting for > 30 seconds or requiring repeat ablation, hospital admission, cardioversion or antiarrhythmic drug (AAD) therapy* after ablation. (Both trials) Quality of Life (QOL) score. (Both trials) Procedural complications including cardiac tamponade, thromboembolism, PV stenosis/occlusion, left atrium-esophageal fistula, and peri-esophageal injury. (UNDER-ATP trial) Total procedure time. (UNDER-ATP trial) Total fluoroscopy time. (UNDER-ATP trial) Total radiation dose. (UNDER-ATP trial) Total number and duration of radiofrequency energy applications. (UNDER-ATP trial) Total number and duration of radiofrequency energy applications for pulmonary vein isolation. (UNDER-ATP trial) Side effects of ATP including bronchial asthma, angina and sustained hypotension (<90mmHg or requiring vasopressor) during and after the procedure. (UNDER-ATP trial) Side effects of antiarrhythmic drugs (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.
Eligibility
Minimum age: 21 Years.
Maximum age: 79 Years.
Gender(s): Both.
Criteria:
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)
Locations and Contacts
Division of Cardiology, Kyoto University Hospital, Kyoto 606-8507, Japan
Additional Information
Starting date: November 2011
Last updated: May 18, 2014
|