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First Line Radiofrequency Ablation Versus Antiarrhythmic Drugs for Atrial Fibrillation Treatment (The RAAFT Study)
This study is currently recruiting participants.
Verified by Population Health Research Institute, October 2007
First Received: October 23, 2006   Last Updated: October 10, 2007   History of Changes
Sponsors and Collaborators: Population Health Research Institute
Johnson & Johnson
Information provided by: Population Health Research Institute
ClinicalTrials.gov Identifier: NCT00392054
  Purpose

The purpose of this study is to determine whether catheter-based pulmonary vein isolation is superior to antiarrhythmic drugs as first line therapy in patients with symptomatic paroxysmal recurrent atrial fibrillation not previously treated with therapeutic doses of antiarrhythmic drugs.


Condition Intervention Phase
Atrial Fibrillation
Procedure: Pulmonary Vein Isolation
Drug: Control Group receives Anti-Arrhythmic Drugs per ACC/AHA 2006 Guidelines for the Management of Patients with AF
Phase III

Genetics Home Reference related topics: Brugada syndrome familial atrial fibrillation short QT syndrome
MedlinePlus related topics: Atrial Fibrillation
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title: First Line Radiofrequency Ablation Versus Antiarrhythmic Drugs for Atrial Fibrillation Treatment: A Multi-Center Randomized Trial

Further study details as provided by Population Health Research Institute:

Primary Outcome Measures:
  • Primary Efficacy: Time to first recurrence of electrocardiographically documented symptomatic atrial fibrillation lasting >30 seconds during Follow-up Period.
  • Primary Safety: Ablation Arm: Severe (>70%) PV stenosis at 3 and 12 month follow-up. Thromboembolic event with residual sequelae, TIA, pericarditis, myocardial infarction, diaphragmatic paralysis, procedural complication requiring intervention and death.
  • Primary Safety: AAD Arm: Torsade de Pointes, syncope, bradycardia requiring pacemaker, other pro-arrhythmic events, any other significant adverse events leading to drug discontinuation. Bleeding complications associated with OAC therapy.

Secondary Outcome Measures:
  • Secondary Efficacy Outcomes: 1. Total of symptomatic and asymptomatic AF episodes documented by TTM,
  • 2. Quality of life at 1-year follow-up (EQ-5D).

Estimated Enrollment: 400
Study Start Date: August 2006
Estimated Study Completion Date: December 2009
Detailed Description:

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice and is estimated to affect 2.2 million people in the United States. AF is a major cause of stroke, adversely affects quality of life, and is associated with increased mortality. Despite advances in antiarrhythmic drug therapy, AF continues to be associated with significant morbidity. Although antiarrhythmic drug therapy is currently considered a first-line option, recent data indicate that more than 35% of Patients will have recurrence of AF despite best antiarrhythmic drug (AAD) therapy, and more than 30% of Patients will discontinue the drugs because of adverse reactions. Furthermore, although recent trials have indicated equivalence of rhythm and rate control strategies in some patient populations, 25-35% of Patients with AF who are rate controlled will continue to have activity limiting symptoms.

Newer measures to prevent, treat and potentially cure AF are needed. Seminal work by Haissaguerre and replicated by Chen showed that the majority of AF is initiated by ectopic foci found primarily in the pulmonary veins (PV). Experience with the catheter-based Maze technique led to observations that opened the door to effective and practical catheter-based cures for AF. In response to the difficulties of focal ablation, an alternate strategy has been developed that seeks to electrically isolate the Pulmonary Veins from the atrial tissue. Empirical PV isolation targets all of the PV's without regard to the initiation of ectopic beats. The goal is to create entrance block in the PV. Multipolar circular catheters and basket catheters have been developed that facilitate identification of the electrical connections that are present at the junction of the atrium and the PV, and radiofrequency energy is applied in a circumferential fashion until entrance block is achieved. Relative to focal ablation, circumferential PV isolation is simpler to perform, can be completed without inducing AF, has a shorter procedure time, and has a lower incidence of PV stenosis.

Comparison: Patients will have ablation to achieve entrance and/or exit block into all pulmonary veins, compared with patients receiving antiarrhythmic drugs given in accordance with ACC/AHA/ESC 2006 Guidelines for the Management of patients with AF.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age > 18 years old
  2. Symptomatic, recurrent paroxysmal AF lasting > 30 seconds (at least 4 episodes within the prior 6 months). At least one episode must be documented by Holter, 12-lead ECG, event monitor or rhythm strip.

Exclusion Criteria:

  1. Documented LVEF <40%.
  2. Documented left atrial diameter >5.5cm.
  3. Moderate to severe LVH (LV wall thickness >1.5cm).
  4. Documented valvular disease, coronary heart disease (defined as the presence of >70% stenosis of coronary arteries or documentation of active myocardial ischemia), post-CABG, postoperative cardiac surgery or peripheral artery disease.
  5. Documented AF with electrical cardioversion where full therapeutic antiarrhythmic drug therapy after the cardioversion was prescribed.
  6. Untreated hypothyroidism or hyperthyroidism. Patients who are euthyroid on thyroid hormone replacement therapy are acceptable.
  7. Contraindication for the use of sotalol, dofetilide and 1C antiarrhythmic drugs (liver enzymes and serum creatinine that are outside the upper normal lab values, e.g. > 3 times ULN with 2 abnormal lab values).
  8. Previous left heart ablation procedure, either by surgery or by percutaneous catheter, for atrial fibrillation.
  9. Current enrollment in another investigational drug or device study.
  10. Presence of any other condition that the investigator feels would be problematic or would restrict or limit the participation of the Patient for the entire study period.
  11. Absolute contra-indication to the use of heparin and or warfarin.
  12. Increase risk of bleeding, current peptic ulceration, proliferative diabetic retinopathy, history of severe systemic bleeding, or other history of bleeding diathesis or coagulopathy.
  13. Severe pulmonary disease e.g. restrictive pulmonary disease, chronic obstructive disease (COPD).
  14. Documented intra-atrial thrombus, tumor, or another abnormality which precludes catheter introduction.
  15. Previous use of full therapeutic dose of an antiarrhythmic drug, including amiodarone, propafenone, flecainide, sotalol, quinidine.
  16. Pacemaker or Implantable Cardioverter Defibrillator.
  17. Females of childbearing potential who are not practicing protocol acceptable method of birth control.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00392054

Contacts
Contact: Carlos A Morillo, MD (905) 577-8004 morillo@hhsc.ca
Contact: Rashid J Ahmed, BScH (905) 527-4322 ext 44556 rashid@phri.ca

Locations
Canada, Ontario
Hamilton General Hospital Recruiting
Hamilton, Ontario, Canada, L8L 2X2
Contact: Rashid J Ahmed, B.Sc.H.     (905) 527-4322 ext 44556     rashid@phri.ca    
Contact: Carlos A Morillo, MD     (905) 577-8004     morillo@hhsc.ca    
Principal Investigator: Carlos A Morillo, MD            
Sub-Investigator: Stuart Connolly, MD            
Sub-Investigator: Jeffry Healey, MD            
Sub-Investigator: Girish Nair, MD            
Sub-Investigator: S. Divakaramenon, MD            
Sub-Investigator: P. Neary, MD            
Sponsors and Collaborators
Population Health Research Institute
Johnson & Johnson
Investigators
Principal Investigator: Carlos A Morillo, MD Population Health Research Institute, Hamilton Health Sciences Corporation and McMaster University
Principal Investigator: Natale Andrea, MD Unaffiliated
  More Information

Additional Information:
Publications:
Benjamin EJ, Wolf PA, D'Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation. 1998 Sep 8;98(10):946-52.
European Heart Rhythm Association; Heart Rhythm Society; Fuster V, Ryden LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, Halperin JL, Le Heuzey JY, Kay GN, Lowe JE, Olsson SB, Prystowsky EN, Tamargo JL, Wann S, Smith SC Jr, Jacobs AK, Adams CD, Anderson JL, Antman EM, Hunt SA, Nishimura R, Ornato JP, Page RL, Riegel B, Priori SG, Blanc JJ, Budaj A, Camm AJ, Dean V, Deckers JW, Despres C, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A, Zamorano JL; American College of Cardiology; American Heart Association Task Force on Practice Guidelines; European Society of Cardiology Committee for Practice Guidelines; Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation--executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation). J Am Coll Cardiol. 2006 Aug 15;48(4):854-906. No abstract available.
Haissaguerre M, Jais P, Shah DC, Gencel L, Pradeau V, Garrigues S, Chouairi S, Hocini M, Le Metayer P, Roudaut R, Clementy J. Right and left atrial radiofrequency catheter therapy of paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol. 1996 Dec;7(12):1132-44.
Haissaguerre M, Jais P, Shah DC, Takahashi A, Hocini M, Quiniou G, Garrigue S, Le Mouroux A, Le Metayer P, Clementy J. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med. 1998 Sep 3;339(10):659-66.
Chen SA, Tai CT, Tsai CF, Hsieh MH, Ding YA, Chang MS. Radiofrequency catheter ablation of atrial fibrillation initiated by pulmonary vein ectopic beats. J Cardiovasc Electrophysiol. 2000 Feb;11(2):218-27. Review.
Haissaguerre M, Jais P, Shah DC, Garrigue S, Takahashi A, Lavergne T, Hocini M, Peng JT, Roudaut R, Clementy J. Electrophysiological end point for catheter ablation of atrial fibrillation initiated from multiple pulmonary venous foci. Circulation. 2000 Mar 28;101(12):1409-17.
Marrouche NF, Dresing T, Cole C, Bash D, Saad E, Balaban K, Pavia SV, Schweikert R, Saliba W, Abdul-Karim A, Pisano E, Fanelli R, Tchou P, Natale A. Circular mapping and ablation of the pulmonary vein for treatment of atrial fibrillation: impact of different catheter technologies. J Am Coll Cardiol. 2002 Aug 7;40(3):464-74.
Ng FS, Camm AJ. Catheter ablation of atrial fibrillation. Clin Cardiol. 2002 Aug;25(8):384-94. Review.
Oral H, Chugh A, Good E, Igic P, Elmouchi D, Tschopp DR, Reich SS, Bogun F, Pelosi F Jr, Morady F. Randomized comparison of encircling and nonencircling left atrial ablation for chronic atrial fibrillation. Heart Rhythm. 2005 Nov;2(11):1165-72.
Wazni OM, Marrouche NF, Martin DO, Verma A, Bhargava M, Saliba W, Bash D, Schweikert R, Brachmann J, Gunther J, Gutleben K, Pisano E, Potenza D, Fanelli R, Raviele A, Themistoclakis S, Rossillo A, Bonso A, Natale A. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: a randomized trial. JAMA. 2005 Jun 1;293(21):2634-40.
Scherlag BJ, Yamanashi W, Patel U, Lazzara R, Jackman WM. Autonomically induced conversion of pulmonary vein focal firing into atrial fibrillation. J Am Coll Cardiol. 2005 Jun 7;45(11):1878-86.
Nademanee K, McKenzie J, Kosar E, Schwab M, Sunsaneewitayakul B, Vasavakul T, Khunnawat C, Ngarmukos T. A new approach for catheter ablation of atrial fibrillation: mapping of the electrophysiologic substrate. J Am Coll Cardiol. 2004 Jun 2;43(11):2044-53.

Study ID Numbers: USMay1/07CANAug1/06EUJan1/07
Study First Received: October 23, 2006
Last Updated: October 10, 2007
ClinicalTrials.gov Identifier: NCT00392054     History of Changes
Health Authority: United States: Food and Drug Administration;   Canada: Health Canada;   European Union: European Medicines Agency

Keywords provided by Population Health Research Institute:
Atrial Fibrillation
Paroxysmal
Pulmonary Vein Isolation
Ablation Catheter
Anti-arrhythmic Drug Therapy
First Line Therapy

Study placed in the following topic categories:
Heart Diseases
Cardiovascular Agents
Anti-Arrhythmia Agents
Atrial Fibrillation
Arrhythmias, Cardiac

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

ClinicalTrials.gov processed this record on May 07, 2009