Kansai Plus Atrial Fibrillation Trial (KPAF)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Satoshi Shizuta, Kyoto University, Graduate School of Medicine
ClinicalTrials.gov Identifier:
NCT01477983
First received: November 12, 2011
Last updated: May 18, 2014
Last verified: May 2014
  Purpose

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).


Condition Intervention Phase
Atrial Fibrillation
Procedure: ATP guide additional ablation.
Drug: Antiarrhythmic drug (AAD)
Drug: Control
Procedure: Control
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Kyoto University, Graduate School of Medicine:

Primary Outcome Measures:
  • 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) [ Time Frame: 91 - 365 days ] [ Designated as safety issue: No ]

    Atrial tachyarrhythmias include atrial fibrillation, atrial tachycardia, and common or uncommon atrial flutter.

    Antiarrhythmic drug (AAD) indicates Vaughan Williams class I or III drug.



Secondary Outcome Measures:
  • Repeat Ablation for atrial tachyarrhythmias. (Both trials) [ Time Frame: 0 - 365 days ] [ Designated as safety issue: No ]
  • 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) [ Time Frame: 0 - 90 days ] [ Designated as safety issue: No ]
    * In patients assigned to AAD group, AAD therapy between 0 and 90 days post ablation is not regarded as this secondary outcome.

  • Atrial tachyarrhythmias lasting for > 30 seconds or requiring repeat ablation, hospital admission, cardioversion or antiarrhythmic drug (AAD) therapy* after ablation. (Both trials) [ Time Frame: 0 - 365 days ] [ Designated as safety issue: No ]
    * In patients assigned to AAD group, AAD therapy between 0 and 90 days post ablation is not regarded as this secondary outcome.

  • Quality of Life (QOL) score. (Both trials) [ Time Frame: 0 - 365 days ] [ Designated as safety issue: No ]
    Atrial Fibrillation Quality of Life Questionnaire(AFQLQ) is used in this study.

  • Procedural complications including cardiac tamponade, thromboembolism, PV stenosis/occlusion, left atrium-esophageal fistula, and peri-esophageal injury. (UNDER-ATP trial) [ Time Frame: 0 - 365 days ] [ Designated as safety issue: Yes ]
  • Total procedure time. (UNDER-ATP trial) [ Time Frame: Day-0 ] [ Designated as safety issue: Yes ]
  • Total fluoroscopy time. (UNDER-ATP trial) [ Time Frame: Day-0 ] [ Designated as safety issue: Yes ]
  • Total radiation dose. (UNDER-ATP trial) [ Time Frame: Day-0 ] [ Designated as safety issue: Yes ]
  • Total number and duration of radiofrequency energy applications. (UNDER-ATP trial) [ Time Frame: Day-0 ] [ Designated as safety issue: Yes ]
  • Total number and duration of radiofrequency energy applications for pulmonary vein isolation. (UNDER-ATP trial) [ Time Frame: Day-0 ] [ Designated as safety issue: Yes ]
  • Side effects of ATP including bronchial asthma, angina and sustained hypotension (<90mmHg or requiring vasopressor) during and after the procedure. (UNDER-ATP trial) [ Time Frame: 0 - 365 days ] [ Designated as safety issue: Yes ]
  • Side effects of antiarrhythmic drugs (EAST-AF trial) [ Time Frame: 0 - 365 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 2000
Study Start Date: November 2011
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: ATP guide additional ablation - AAD
UNDER-ATP trial: ATP guide additional ablation, EAST-AF trial: AAD for 90 days
Procedure: ATP guide additional ablation.
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.
Other Name: The brand names of ATP; Adetphos-L, Trinosin-S
Drug: Antiarrhythmic drug (AAD)
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.
Other Name: Brand names; Tambocor, Pronon, Sotacor, Ancaron
Active Comparator: Control - AAD
UNDER-ATP trial: Control, EAST-AF trial: AAD for 90 days
Procedure: Control
Following successful PV isolation, intravenous ATP is not administered.
Other Name: The brand names of ATP; Adetphos-L, Trinosin-S
Drug: Antiarrhythmic drug (AAD)
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.
Other Name: Brand names; Tambocor, Pronon, Sotacor, Ancaron
Active Comparator: ATP guide additinal ablation - Control
UNDER-ATP trial: ATP guide additional ablation, EAST-AF trial: Control
Procedure: ATP guide additional ablation.
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.
Other Name: The brand names of ATP; Adetphos-L, Trinosin-S
Drug: Control
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 Name: Brand names; Tambocor, Pronon, Sotacor, Ancaron
Active Comparator: Control - Control
UNDER-ATP trial: Control, EAST-AF trial: Control
Procedure: Control
Following successful PV isolation, intravenous ATP is not administered.
Other Name: The brand names of ATP; Adetphos-L, Trinosin-S
Drug: Control
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 Name: Brand names; Tambocor, Pronon, Sotacor, Ancaron

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

Ages Eligible for Study:   21 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01477983

Locations
Japan
Division of Cardiology, Kyoto University Hospital
Kyoto, Japan, 606-8507
Sponsors and Collaborators
Kyoto University, Graduate School of Medicine
Investigators
Principal Investigator: Satoshi Shizuta, MD Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine
  More Information

No publications provided

Responsible Party: Satoshi Shizuta, Satoshi Shizuta, Kyoto University, Graduate School of Medicine, Kyoto University, Graduate School of Medicine
ClinicalTrials.gov Identifier: NCT01477983     History of Changes
Other Study ID Numbers: KPAFKUHP
Study First Received: November 12, 2011
Last Updated: May 18, 2014
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Kyoto University, Graduate School of Medicine:
atrial fibrillation
catheter ablation
adenosine triphosphate
antiarrhythmic drugs

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Anti-Arrhythmia Agents
Flecainide
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 29, 2014