Atrial Fibrillation Progression Trial

Phase 4

Terminated

Conditions: Atrial Fibrillation

Interventions: Device: Catheter Ablation
Drug: Drug Treatment

Registration Number: NCT01570361

Lead Sponsor: Biosense Webster, Inc.

Brief Summary: The objective of this study is to determine whether early radiofrequency (RF) ablation treatment, using the CARTO® 3 or CARTO® XP System, and THERMOCOOL® Catheter Family (including THERMOCOOL® SF or THERMOCOOL® SMARTTOUCH™) in subjects with paroxysmal atrial fibrillation (PAF), delays progression of atrial fibrillation (AF) compared with drug therapy (either rate or rhythm control) using current AF management guidelines.

Detailed Description: Eligible PAF subjects with recurrent AF for 2 years who have failed no more than 2 prescribed drugs (with either anti-arrhythmic or rate control drug) are randomized into one of two study arms (catheter ablation or drug therapy).

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 255

Inclusion Criteria

Patients with recurrent paroxysmal atrial fibrillation (AF) for at least 2 years, with ≥ 2 episodes over the last 6 months; (per Amendment v3, 09APR2013, previous "6 episodes" )
HATCH Score of at least ≥1 and ≤4.
Eligible for catheter ablation and for anti-arrhythmic or rate control medications, after having failed at least 1 but no more than 2 prescribed drugs (either anti-arrhythmic or rate control drug).
Age 60 years or older.
Left atrium (LA) diameter ≤ 55mm by TTE.
Left ventricle (LV) ejection fraction ≥50% when in sinus rhythm or LV ejection fraction ≥35% when in atrial fibrillation.

NOTE: For patients entering the study in AF with an ejection fraction ≥35% and <50%; the ejection fraction should be re-checked when in sinus rhythm. In case the ejection fraction is >50% the subject can continue in the study.
Patient signed the Informed Consent Form and is able and willing to comply with protocol requirements, including all baseline and follow-up testing.

Exclusion Criteria

Patients awaiting cardiac transplantation or other cardiac surgery.
Acute illness (ongoing) or active systemic infection or sepsis which in the opinion of the investigator, may adversely affect the safety and/or effectiveness of the participant of the study.
Reversible causes of atrial fibrillation, e.g. but not limited to thyroid disorders, acute alcohol intoxication, recent major surgical procedures or trauma, etc.
Recent cardiac events including myocardial infarction (MI), percutaneous coronary intervention (PCI), or valve or bypass surgery in the preceding 3 months.
Heart failure decompensation.
Previously diagnosed with persistent/permanent atrial fibrillation/ atrial flutter.
Previously required cardioversion >48 hours after onset of atrial fibrillation/ atrial flutter.
Subject having previous transischemic attack (TIA) or stroke (cerebrovascular accident) one year prior to patient enrolment and/or no sufficient recovery.
Pulmonary embolism or recent atrial embolism/thrombosis.
Hypertrophic obstructive cardiomyopathy.
Class IV angina or Class IV congestive heart failure (CHF) (including past or planned heart transplantation).
Mandated anti-arrhythmic drug therapy for disease conditions other than atrial fibrillation.
Heritable arrhythmias or increased risk for torsade de pointes with class I or III Drugs.
Prior left atrial catheter ablation with the intention of treating atrial fibrillation; prior surgical interventions for AF such as the MAZE procedure.
Prior AV nodal ablation.
Patients presenting contra-indications for the study catheter(s), as indicated in the respective Instructions For Use.
Contraindication to warfarin, other anticoagulation therapy, or all anti-platelet medications.
Medical conditions limiting expected survival to <3 years.
Concurrent participation in any other clinical study.
Prior history of non-adherence to prescribed drug regimens.
Women of child bearing potential whom are pregnant, lactating, or planning to become pregnant during the course of the trial

NOTE: Prior ablation of the cavo-tricuspid isthmus is not a reason to exclude, if the patient develops subsequent recurrent atrial fibrillation.

NOTE: For patients randomized to the PVI group (Test Group), a Transesophageal Echocardiography (TEE) should be performed (as per standard of care), within 48 hours pre-procedure, to exclude atrial thrombus or other structural contraindications for an ablation procedure.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Catheter Ablation	Catheter Ablation	Radiofrequency catheter ablation treatment in subjects with Paroxysmal Atrial Fibrillation (PAF)
Drug Treatment	Drug Treatment	Drug therapy (either rate or rhythm control) using current AF management guidelines

Primary Outcome Measures

Name	Time	Method
Time to Persistent Atrial Fibrillation/Atrial Tachycardia at 3 Years	3 years	Persistent atrial fibrillation/atrial tachycardia (AF/AT) (excluding isthmus-dependent atrial flutter) was defined as AF/AT lasting longer than 7 consecutive days or requiring termination by cardioversion after 48 hours.

Secondary Outcome Measures

Name	Time	Method
Time to Persistent Atrial Fibrillation/Atrial Tachycardia at 2 Years	2 years	Persistent atrial fibrillation/atrial tachycardia (AF/AT) (excluding isthmus-dependent atrial flutter) was defined as AF/AT lasting longer than 7 consecutive days or requiring termination by cardioversion after 48 hours.
Number of Repeat Ablations	3 years	Number of repeat ablations refers to the total number of ablation procedures (including initial ablation procedure). If the number of repeat ablations =1 then subject only had one ablation procedure (initial ablation procedure in test group as randomized or cross-over procedure in cross-over subjects). If the number of repeat ablations is \>= 2, then subject had at least one repeat procedure.
Percentage of Participants With Persistent Atrial Fibrillation/Atrial Tachycardia at 1 Year	1 year	Percentage of Participants with Persistent Atrial Fibrillation/Atrial Tachycardia at 1 year were reported. The percentage of participants was calculated using Kaplan Meier (KM) rate estimate. Persistent atrial fibrillation/atrial tachycardia (AF/AT) (excluding isthmus-dependent atrial flutter) was defined as AF/AT lasting longer than 7 consecutive days or requiring termination by cardioversion after 48 hours.
Percentage of Participants With Persistent Atrial Fibrillation/Atrial Tachycardia at 3 Year	3 year	Percentage of Participants with Persistent Atrial Fibrillation/Atrial Tachycardia at 3 year were reported. The percentage of participants was calculated using Kaplan Meier (KM) rate estimate. Persistent atrial fibrillation/atrial tachycardia (AF/AT) (excluding isthmus-dependent atrial flutter) was defined as AF/AT lasting longer than 7 consecutive days or requiring termination by cardioversion after 48 hours.
Time to Persistent Atrial Fibrillation/Atrial Tachycardia at 1 Year	1 year	Persistent atrial fibrillation/atrial tachycardia (AF/AT) (excluding isthmus-dependent atrial flutter) was defined as AF/AT lasting longer than 7 consecutive days or requiring termination by cardioversion after 48 hours.
Number of Participants in Sinus Rhythm at Each Visit Throughout the Follow-up	3 months, 6 months, 1 year, 2 years, 3 years	Subject in sinus rhythm: no other rhythms documented at specific visit, based on ECG, Holter and event recorder. Percentages are calculated with respect to number of subjects with data available at corresponding visit
Number of Participants With Recurrent AF/AT at Each Visit Throughout the Follow-up	3 months, 6 months, 1 year, 2 year and 3 years	Subjects with recurrent AF/AT: any AF/AT documented between previous visit up to visit analyzed at any TTM, Holter or ECG. Percentages are calculated with respect to number of subjects with data available at corresponding visit
Percentage of Participants With Persistent Atrial Fibrillation/Atrial Tachycardia at 2 Years	2 Years	Percentage of Participants with Persistent Atrial Fibrillation/Atrial Tachycardia at 2 year were reported. The percentage of participants was calculated using Kaplan Meier (KM) rate estimate. Persistent atrial fibrillation/atrial tachycardia (AF/AT) (excluding isthmus-dependent atrial flutter) was defined as AF/AT lasting longer than 7 consecutive days or requiring termination by cardioversion after 48 hours.
Percentage of Participants With Persistent Atrial Fibrillation/Atrial Tachycardia at 3 Years by Number of Repeat Ablations	3 years	Percentage of Participants with Persistent Atrial Fibrillation/Atrial Tachycardia at 3 year by number of repeat ablations were reported. The percentage of participants was calculated using Kaplan Meier (KM) rate estimate. Persistent atrial fibrillation/atrial tachycardia (AF/AT) (excluding isthmus-dependent atrial flutter) was defined as AF/AT lasting longer than 7 consecutive days or requiring termination by cardioversion after 48 hours.
Number of New Antiarrhythmic Drugs	3 years	Number of new antiarrhythmic drugs were administered as per investigator's discretion and 2006 AF management guidelines.

Trial Locations

Locations (36): Vivantes Klinikum am Urban
🇩🇪
Berlin, Germany
Korea University Anam Hospital
🇰🇷
Seoul, Korea, Republic of
University Heart Center Hamburg-Eppendorf
🇩🇪
Hamburg, Germany
Herzpraxis Altona
🇩🇪
Hamburg, Germany
Policlinico Casalino Roma
🇮🇹
Roma, Italy
Asklepios Klinik St. Georg
🇩🇪
Hamburg, Germany
Ospedaleria Universitaria Pisana
🇮🇹
Pisa, Italy
University Hospital of South Manchester
🇬🇧
Manchester, United Kingdom
Hospital Universitario Virgen de la Victoria
🇪🇸
Malaga, Spain
Asan Medical Center
🇰🇷
Seoul, Korea, Republic of
Hospital Universitario Infanta Leonor
🇪🇸
Madrid, Spain
State Research Institute of Circulation Pathology
🇷🇺
Novosibirsk, Russian Federation
Ospedale Generale Regionale "F. Miulli"
🇮🇹
Bari, Italy
Hospital Universitario Salamanca
🇪🇸
Salamanca, Spain
Hospital General Universitario Gregorio Maranon
🇪🇸
Madrid, Spain
P. Stradins Clinical University Hospital
🇱🇻
Riga, Latvia
Federal State Institution National Research Center for Preventive Medicine of Healthcare of the Russian Federation
🇷🇺
Moscow, Russian Federation
Papworth Hospital
🇬🇧
Cambridge, United Kingdom
Royal Bournemouth Hospital
🇬🇧
Bournemouth, United Kingdom
Semmelweis University, Cardiovascular Center
🇭🇺
Budapest, Hungary
Mater Misericordiae University Hospital
🇮🇪
Dublin, Ireland
Krankenhaus der Elisabethinen
🇦🇹
Linz, Austria
Haukeland Universitetssykehus
🇳🇴
Bergen, Norway
Kerckhoff Klinik
🇩🇪
Bad Nauheim, Germany
Royal Adelaide Hospital
🇦🇺
Adelaide, Australia
Medizinische Universitaetsklinik
🇦🇹
Graz, Austria
OLV Ziekenhuis
🇧🇪
Aalst, Belgium
AZ Sint Jan
🇧🇪
Brugge, Belgium
Helios Klinikum Berlin-Buch
🇩🇪
Berlin, Germany
Samsung Medical Center
🇰🇷
Seoul, Korea, Republic of
Cardinal Stefan Wyszyński Institute of Cardiology
🇵🇱
Warszaw, Poland
Federal Center of Cardiovascular Surgery
🇷🇺
Krasnoyarsk, Russian Federation
Almazov Federal Heart, Blood and Endocrinology Centre
🇷🇺
Saint-Petersburg, Russian Federation
Federal State Budgetary Scientific Institution "Research Institute for Cardiology"
🇷🇺
Tomsk, Russian Federation
Herzzentrum Universitätsmedizin Göttingen
🇩🇪
Göttingen, Germany
Universitetssjukhuset Örebro
🇸🇪
Örebro, Sweden