Atrial Fibrillation Progression Trial (ATTEST)

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.

Study Overview

• Status: Terminated
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Device: Catheter Ablation; Drug: Drug Treatment

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).

• Study Type: Interventional
• Enrollment (Actual): 255
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia, 5000
    • Royal Adelaide Hospital
• Austria
  • Graz, Austria, 8036
    • Medizinische Universitaetsklinik
  • Linz, Austria, 4020
    • Krankenhaus der Elisabethinen
• Belgium
  • Aalst, Belgium, 9300
    • OLV Ziekenhuis
  • Brugge, Belgium, 8000
    • AZ Sint Jan
• Germany
  • Bad Nauheim, Germany, 61231
    • Kerckhoff Klinik
  • Berlin, Germany, 13125
    • Helios Klinikum Berlin-Buch
  • Berlin, Germany, 10967
    • Vivantes Klinikum am Urban
  • Göttingen, Germany, 37099
    • Herzzentrum Universitätsmedizin Göttingen
  • Hamburg, Germany, 20099
    • Asklepios Klinik St. Georg
  • Hamburg, Germany, 22765
    • Herzpraxis Altona
  • Hamburg, Germany, 20246
    • University Heart Center Hamburg-Eppendorf
• Hungary
  • Budapest, Hungary, 1122
    • Semmelweis University, Cardiovascular Center
• Ireland
  • Dublin, Ireland, 7
    • Mater Misericordiae University Hospital
• Italy
  • Bari, Italy, 70021
    • Ospedale Generale Regionale "F. Miulli"
  • Pisa, Italy, 56126
    • Ospedaleria Universitaria Pisana
  • Roma, Italy, 00169
    • Policlinico Casalino Roma
• Korea, Republic of
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 02841
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
• Latvia
  • Riga, Latvia, 1002
    • P. Stradins Clinical University Hospital
• Norway
  • Bergen, Norway, 5021
    • Haukeland Universitetssykehus
• Poland
  • Warszaw, Poland, 04-628
    • Cardinal Stefan Wyszyński Institute of Cardiology
• Russian Federation
  • Krasnoyarsk, Russian Federation, 45
    • Federal Center of Cardiovascular surgery
  • Moscow, Russian Federation, 101990
    • Federal State Institution National Research Center for Preventive Medicine of Healthcare of the Russian Federation
  • Novosibirsk, Russian Federation, 55
    • State Research Institute of Circulation Pathology
  • Saint-Petersburg, Russian Federation, 194341
    • Almazov Federal Heart, Blood and Endocrinology Centre
  • Tomsk, Russian Federation, 634012
    • Federal State Budgetary Scientific Institution "Research Institute for Cardiology"
• Spain
  • Madrid, Spain, 28009
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain, 28007
    • Hospital Universitario Infanta Leonor
  • Malaga, Spain, 29010
    • Hospital Universitario Virgen De La Victoria
  • Salamanca, Spain, 37007
    • Hospital Universitario Salamanca
• Sweden
  • Örebro, Sweden, 701 85
    • Universitetssjukhuset Örebro
• United Kingdom
  • Bournemouth, United Kingdom, BH7 7DW
    • Royal Bournemouth Hospital
  • Cambridge, United Kingdom, CB23 3RE
    • Papworth Hospital
  • Manchester, United Kingdom, M23 9LT
    • University Hospital of South Manchester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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" )
2. HATCH Score of at least ≥1 and ≤4.
3. 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).
4. Age 60 years or older.
5. Left atrium (LA) diameter ≤ 55mm by TTE.

6. 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.

7. 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:

1. Patients awaiting cardiac transplantation or other cardiac surgery.
2. 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.
3. Reversible causes of atrial fibrillation, e.g. but not limited to thyroid disorders, acute alcohol intoxication, recent major surgical procedures or trauma, etc.
4. Recent cardiac events including myocardial infarction (MI), percutaneous coronary intervention (PCI), or valve or bypass surgery in the preceding 3 months.
5. Heart failure decompensation.
6. Previously diagnosed with persistent/permanent atrial fibrillation/ atrial flutter.
7. Previously required cardioversion >48 hours after onset of atrial fibrillation/ atrial flutter.
8. Subject having previous transischemic attack (TIA) or stroke (cerebrovascular accident) one year prior to patient enrolment and/or no sufficient recovery.
9. Pulmonary embolism or recent atrial embolism/thrombosis.
10. Hypertrophic obstructive cardiomyopathy.
11. Class IV angina or Class IV congestive heart failure (CHF) (including past or planned heart transplantation).
12. Mandated anti-arrhythmic drug therapy for disease conditions other than atrial fibrillation.
13. Heritable arrhythmias or increased risk for torsade de pointes with class I or III Drugs.
14. Prior left atrial catheter ablation with the intention of treating atrial fibrillation; prior surgical interventions for AF such as the MAZE procedure.
15. Prior AV nodal ablation.
16. Patients presenting contra-indications for the study catheter(s), as indicated in the respective Instructions For Use.
17. Contraindication to warfarin, other anticoagulation therapy, or all anti-platelet medications.
18. Medical conditions limiting expected survival to <3 years.
19. Concurrent participation in any other clinical study.
20. Prior history of non-adherence to prescribed drug regimens.
21. 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Catheter Ablation; Radiofrequency catheter ablation treatment in subjects with Paroxysmal Atrial Fibrillation (PAF)	Device: Catheter Ablation; Treat subjects with Paroxysmal Atrial Fibrillation (PAF); Other Names: CARTO® 3 or CARTO® XP System and THERMOCOOL® Catheter Family
Active Comparator: Drug Treatment; Drug therapy (either rate or rhythm control) using current AF management guidelines	Drug: Drug Treatment; Drug therapy (either rate or rhythm control): Class I or class III, or AV nodal blocking agents such as beta blockers and calcium channel blockers in accordance with current atrial fibrillation management guidelines.; Other Names: Antiarrhythmic Drugs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Persistent Atrial Fibrillation/Atrial Tachycardia at 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.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Persistent Atrial Fibrillation/Atrial Tachycardia at 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.	1 year
Time to Persistent Atrial Fibrillation/Atrial Tachycardia at 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.	2 years
Percentage of Participants With Persistent Atrial Fibrillation/Atrial Tachycardia at 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.	1 year
Percentage of Participants With Persistent Atrial Fibrillation/Atrial Tachycardia at 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.	2 Years
Percentage of Participants With Persistent Atrial Fibrillation/Atrial Tachycardia at 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.	3 year
Percentage of Participants With Persistent Atrial Fibrillation/Atrial Tachycardia at 3 Years by Number of Repeat Ablations	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.	3 years
Number of Repeat Ablations	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.	3 years
Number of New Antiarrhythmic Drugs	Number of new antiarrhythmic drugs were administered as per investigator's discretion and 2006 AF management guidelines.	3 years
Number of Participants in Sinus Rhythm at Each Visit Throughout the Follow-up	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	3 months, 6 months, 1 year, 2 years, 3 years
Number of Participants With Recurrent AF/AT at Each Visit Throughout the Follow-up	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	3 months, 6 months, 1 year, 2 year and 3 years

Collaborators and Investigators

• Sponsor: Biosense Webster, Inc.
• Investigators: Principal Investigator: Karl-Heinz Kuck, MD, Asklepios Klinik St. Georg

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2012
• Primary Completion (Actual): December 19, 2018
• Study Completion (Actual): December 19, 2018

Study Registration Dates

• First Submitted: March 28, 2012
• First Submitted That Met QC Criteria: April 3, 2012
• First Posted (Estimate): April 4, 2012

Study Record Updates

• Last Update Posted (Actual): May 14, 2020
• Last Update Submitted That Met QC Criteria: May 1, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Pathologic Processes; Atrial Fibrillation; Cardiovascular Diseases; Heart Diseases; Arrhythmias, Cardiac
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Anti-Arrhythmia Agents
• Other Study ID Numbers: ATTEST

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes