A Trial of Circumferential Pulmonary Vein Ablation (CPVA) Versus Antiarrhythmic Drug Therapy in for Paroxysmal Atrial Fibrillation (AF) (APAF2)

This study has been completed.
Sponsor:
Information provided by:
IRCCS San Raffaele
ClinicalTrials.gov Identifier:
NCT00340314
First received: June 19, 2006
Last updated: July 27, 2010
Last verified: May 2006
  Purpose

Background: Circumferential pulmonary vein ablation (CPVA) has been safely and effectively performed for treating paroxysmal atrial fibrillation (PAF); however, its safety and efficacy, as compared with those of antiarrhythmic drug therapy (ADT), have never been formally assessed in a randomized controlled trial.

The Purpose of this study was to evaluate CPVA versus ADT in patients with PAF in a randomized controlled trial.


Condition Intervention Phase
Atrial Fibrillation
Procedure: Circumferential Pulmonary Vein Ablation
Drug: Antiarrhythmic Drug Therapy
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Controlled Randomized Trial of Circumferential Pulmonary Vein Ablation Versus Antiarrhythmic Drug Therapy in Treating Paroxysmal Atrial Fibrillation. The Ablation for Paroxysmal Atrial Fibrillation (APAF2) Trial

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Further study details as provided by IRCCS San Raffaele:

Primary Outcome Measures:
  • The primary end point was freedom from recurrent atrial tachyarrhythmias ([AT], both AF and regular atrial tachycardia) during a 12 and 48 months follow-up . The first analysis was scheduled to be performed after the last enrolled patient complete.

Secondary Outcome Measures:
  • Presence of SR during 1-month intervals
  • Percent of patients totally free of AF
  • Number of cardioversions
  • LV function
  • Incidence of cardiovascular hospitalization
  • Overall morbidity
  • Left atrial size and function
  • Thromboembolic and bleeding complications
  • Efficacy and safety of two 3D mapping systems
  • Efficacy and safety of two ablation catheters
  • Procedure duration, length of hospital stay

Estimated Enrollment: 198
Study Start Date: January 2005
Estimated Study Completion Date: May 2006
Detailed Description:

Antiarrhythmic drug therapy (ADT) is currently considered as first-line therapy in patients with paroxysmal atrial fibrillation (AF).1 However antiarrhythmic drugs are frequently ineffective and can have serious potential adverse effects, thus often offsetting any advantage offered by the maintenance of sinus rhythm (SR).2,3 Data from our and other laboratories suggest that pulmonary vein ablation techniques may be a curative alternative for AF, obviating the need for ADT and/or anticoagulation in many patients.4-8 However, only preliminary and frequently non-randomized data exists for an evidence-based evaluation of catheter ablation as compared to conventional antiarrhythmic drug therapyADT.4,8 Thus, we conducted a controlled randomized trial (the Ablation for Paroxysmal Atrial Fibrillation [APAF] trial) to determine the long-term efficacy of circumferential pulmonary vein ablation (CPVA) in patients with paroxysmal AF as compared with ADT with flecainide, sotalol or amiodarone.

Methods: One hundred ninety-eight patients (age, 56±10 years) with PAF (duration, 6±5 years, mean AF episodes 3.4/month), were randomized to CPVA or to ADT with flecainide, sotalol or amiodarone. Ablation was randomly performed with the use of a standard or an irrigated tip catheter and with CARTO or NavX non fluoroscopic 3D systems guidance. Cardiac rhythm was assessed with daily transtelephonic transmissions over a 12 and 48 months follow-up. Crossovers to CPVA were allowed after 3 months of ADT.

Results: By Kaplan-Meier analysis, 86% of patients in the CPVA group and 22% in the ADT group were free from recurrent atrial tachyarrhythmias ([AT] P<0.001); a repeat ablation was performed in 9% of patients in the CPVA group for recurrent AF (6%) or atrial tachycardia (3%). At 1 year, 93% and 35% of the CPVA and ADT groups were AT-free while at 4 years only 72.7% patients assigned to RFA and 12.1% assigned to AADs reached the endpoint(p<0.001).Lower left ejection fraction, arterial hypertension and age independently predicted AF recurrences in the ADT group. CPVA was associated with a significant decrease in left atrial diameter (15±10%, P<0.01) and with fewer number of cardiovascular hospitalizations (p<0.01). Ablation with an irrigated tip catheter was more effective (P=0.03) with either the CARTO or NavX system (P=0.08). One transient ischemic attack and one pericardial effusion occurred in the CPVA group; side effects of ADT were reported in 23 patients.During the 4-year follow-up, 87 initially AADs patients required cross over to RFA with a steeper rate at 1 year (42 patients) and 19 of them progressed to persistent AF before switching. Considering repeat ablation and crossover, the overall success rate was 90% in RFA group and 80% in AAD group (p=0.0023, by log-rank test). New left AT developed in 9 patients requiring mapping and ablation in 7 patients. Quality of life was higher in the RFA group than in AAD group for all subscale scores (p<0.001) Conclusions: Compared to ADT, CPVA can safely and effectively cure PAF in many patients at one-year follow-up and this benefit is extended to 4 years.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 18-70 years
  2. History of symptomatic paroxysmal AF lasting more than 6 months. Paroxysms of AF are intended as recurrent self-terminating episodes lasting less than 7 days and occurring more than 2 times every month.

Exclusion Criteria:

  1. Pregnancy
  2. NYHA functional class III or IV
  3. Left atrial size > 65 mm
  4. Left ventricular (LV) ejection fraction < 35%
  5. Contraindication to anticoagulation with warfarin
  6. History of myocardial infarction within six months of the procedure
  7. Prior catheter or surgical ablation attempt for AF
  8. Inability or unwillingness to provide written informed consent
  9. Life expectancy less than 1 year
  10. Significant comorbid conditions such as: cancer (not cured), end stage renal disease (creatinine clearance < 20 mL/h), severe chronic obstructive lung disease, cirrhosis, etc)
  11. Anticipated cardiac surgery for congenital, valvular, aortic or coronary heart disease.
  12. Presence of left atrial thrombus.
  13. Prior antiarrhythmic drug therapy with amiodarone, sotalol and flecainide at optimal doses (target 200 mg, 240 mg, 200 mg daily respectively
  14. AF burden < 2 episodes/month
  15. WPW
  16. Expected survival < 1 year
  17. Contraindications for antiarrhythmics therapy including flecainide, sotalol or amiodarone not listed above:

    • LV hypertrophy (LV mass index > 125g/m2)
    • thyroid dysfunction (hyperthyroidism or uncontrolled hypothyroidism or thyroid cancer)
    • liver dysfunction (ALT or AST >2x the reference values)
    • Interstitial lung disease with DLCO<70% of predicted or severe asthma.
    • QT interval exceeding 400 msec
    • Symptomatic sinus node or atrioventricular node dysfunction unless a pacemaker had been implanted
    • Evidence of stress-induced myocardial ischemia
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00340314

Locations
Italy
San Raffaele University Hospital
Milan, Italy, 20132
Sponsors and Collaborators
IRCCS San Raffaele
Investigators
Principal Investigator: Carlo Pappone, MD, PhD San Raffaele University Hospital, Villa Maria Cecilia Hospital, Cotignola (Ravenna), Italy
Study Chair: Vincenzo Santinelli, MD San Raffaele University Hospital, Villa Maria Cecilia Hospital, Cotignola (Ravenna), Italy
  More Information

Additional Information:
No publications provided by IRCCS San Raffaele

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00340314     History of Changes
Other Study ID Numbers: APAF/02
Study First Received: June 19, 2006
Last Updated: July 27, 2010
Health Authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health

Keywords provided by IRCCS San Raffaele:
symptomatic
paroxysmal
atrial fibrillation

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

ClinicalTrials.gov processed this record on October 20, 2014