Tailored Treatment of Permanent Atrial Fibrillation

Atrial Fibrillation Clinical Trial

— TTOP-AF  

Official title:

Tailored Treatment of Permanent Atrial Fibrillation - TTOP-AF

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00514735
• Other study ID #: AFI-30
• Status: Completed
• Phase: Phase 3
• Start date: May 2007
• Est. completion date: November 2010

Study information

• Verified date: September 2018
• Source: Medtronic Cardiac Rhythm and Heart Failure
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this trial is to evaluate the safety and efficacy of the Medtronic Cardiac Ablation System compared to medical therapy in the persistent and long-standing persistent atrial fibrillation population.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 210
• Est. completion date: November 2010
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

INCLUSION CRITERIA:

• History of symptomatic, continuous atrial fibrillation defined as: Continuous atrial fibrillation lasting greater than 1 year but less than 4 years or nonself-terminating atrial fibrillation, lasting greater than 7 days but no more than 1 year, with at least one failed direct current cardioversion. A failed cardioversion was defined as an unsuccessful cardioversion or one in which normal sinus rhythm was established but not maintained beyond 7 days.

• Atrial fibrillation symptoms included the following: palpitations, fatigue,exertional dyspnea, exercise intolerance

• Age between 18 and 70 years

• Failure of at least one Class I or III rhythm control drug

• Willingness, ability and commitment to participate in baseline and follow-up evaluations for the full length of the study.

EXCLUSION CRITERIA:

• Structural heart disease of clinical significance including:

• Previous cardiac surgery (excluding coronary artery bypass graft and mitral valve repair)

• Symptoms of congestive heart failure including, but not limited to, New York Heart Association (NYHA) Class III or IV congestive heart failure and/or documented ejection fraction <40% measured by acceptable cardiac testing

• Left atrial diameter >55 mm

• Moderate to severe mitral or aortic valvular heart disease

• Stable/unstable angina or ongoing myocardial ischemia

• Myocardial infarction (MI) within 3 months of enrollment

• Congenital heart disease (not including atrial septal defect or patent foramen ovale without a right to left shunt) where the underlying abnormality increases the risk of an ablative procedure

• Prior atrial septal defect of patent foramen ovale closure with a device using a percutaneous approach

• Hypertrophic cardiomyopathy (left ventricular septal wall thickness >1.5 cm)

• Pulmonary hypertension (mean or systolic pulmonary artery pressure >50 mm Hg on Doppler echo)

• Any prior ablation for atrial fibrillation

• Enrollment in any other ongoing arrhythmia study

• Any ventricular tachyarrhythmia currently being treated where the arrhythmia or the management may interfere with this study

• Active infection or sepsis

• Any history of cerebral vascular disease including stroke or transient ischemic attacks

• Pregnancy or lactation

• Left atrial thrombus at the time of ablation

• Untreatable allergy to contrast media

• Any diagnosis of atrial fibrillation secondary to electrolyte imbalance, thyroid disease, or any other reversible or non-cardiovascular causes

• History of blood clotting (bleeding or thrombotic) abnormalities

• Known sensitivities to heparin or warfarin

• Severe chronic obstructive pulmonary disease (defined as forced expiratory volume 1 (FEV1) <1)

• Severe co-morbidity or poor general physical/mental health that, in the opinion of the investigator, will not allow the subject to be a good study candidate

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Procedure:
• Medtronic Cardiac Ablation System
Arm 1 (Ablation Management): Ablation procedures using investigational catheters in left atrium. Cardioversion could be used to restore sinus rhythm if needed.

Drug:
• Class I or III Antiarrhythmic Medications
Arm 2 (Medical Management): Class I or III antiarrhythmic drugs. Changes in dosing, antiarrhythmic drugs or combinations of antiarrhythmic drugs were allowed. Direct current cardioversions were also allowed at the discretion of the investigator.

Locations

Country	Name	City	State
Netherlands	St. Antonius Ziekenhuis	Nieuwegein
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory Crawford Long Hospital	Atlanta	Georgia
United States	Piedmont Hospital	Atlanta	Georgia
United States	Austin Heart	Austin	Texas
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital Cardiac Arrhythmia	Boston	Massachusetts
United States	Lahey Clinic	Burlington	Massachusetts
United States	University of Chicago	Chicago	Illinois
United States	The Ohio State University	Columbus	Ohio
United States	Genesis Medical Center	Davenport	Iowa
United States	Iowa Heart Center	Des Moines	Iowa
United States	Consultants in Cardiovascular Diseases	Erie	Pennsylvania
United States	Spectrum Health Research Department	Grand Rapids	Michigan
United States	Texas Heart Institute at St. Luke's Episcopal	Houston	Texas
United States	Krannert Institute of Cardiology	Indianapolis	Indiana
United States	Mayo Clinic Jacksonville	Jacksonville	Florida
United States	UCLA Cardiac Arrhythmia Center	Los Angeles	California
United States	Sentara Cardiovascular Research Institute	Norfolk	Virginia
United States	University of Rochester	Rochester	New York
United States	Arizona Arrhythmia Research Center	Scottsdale	Arizona
United States	Washington Adventist Hospital	Takoma Park	Maryland
United States	Wake Forest University	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Medtronic Cardiac Rhythm and Heart Failure

Countries where clinical trial is conducted

United States,  Netherlands, 

References & Publications (34)

Abreu Filho CA, Lisboa LA, Dallan LA, Spina GS, Grinberg M, Scanavacca M, Sosa EA, Ramires JA, Oliveira SA. Effectiveness of the maze procedure using cooled-tip radiofrequency ablation in patients with permanent atrial fibrillation and rheumatic mitral valve disease. Circulation. 2005 Aug 30;112(9 Suppl):I20-5. — View Citation

Benussi S, Nascimbene S, Calori G, Denti P, Ziskind Z, Kassem S, La Canna G, Pappone C, Alfieri O. Surgical ablation of atrial fibrillation with a novel bipolar radiofrequency device. J Thorac Cardiovasc Surg. 2005 Aug;130(2):491-7. — View Citation

Chen YJ, Chen SA, Tai CT, Wen ZC, Feng AN, Ding YA, Chang MS. Role of atrial electrophysiology and autonomic nervous system in patients with supraventricular tachycardia and paroxysmal atrial fibrillation. J Am Coll Cardiol. 1998 Sep;32(3):732-8. — View Citation

de Lima GG, Kalil RA, Leiria TL, Hatem DM, Kruse CL, Abrahão R, Sant'anna JR, Prates PR, Nesralla IA. Randomized study of surgery for patients with permanent atrial fibrillation as a result of mitral valve disease. Ann Thorac Surg. 2004 Jun;77(6):2089-94; discussion 2094-5. — View Citation

Dill T, Neumann T, Ekinci O, Breidenbach C, John A, Erdogan A, Bachmann G, Hamm CW, Pitschner HF. Pulmonary vein diameter reduction after radiofrequency catheter ablation for paroxysmal atrial fibrillation evaluated by contrast-enhanced three-dimensional magnetic resonance imaging. Circulation. 2003 Feb 18;107(6):845-50. — View Citation

Dong J, Vasamreddy CR, Jayam V, Dalal D, Dickfeld T, Eldadah Z, Meininger G, Halperin HR, Berger R, Bluemke DA, Calkins H. Incidence and predictors of pulmonary vein stenosis following catheter ablation of atrial fibrillation using the anatomic pulmonary vein ablation approach: results from paired magnetic resonance imaging. J Cardiovasc Electrophysiol. 2005 Aug;16(8):845-52. — View Citation

Earley MJ, Abrams DJ, Staniforth AD, Sporton SC, Schilling RJ. Catheter ablation of permanent atrial fibrillation: medium term results. Heart. 2006 Feb;92(2):233-8. Epub 2005 Aug 23. — View Citation

Fisher JD, Spinelli MA, Mookherjee D, Krumerman AK, Palma EC. Atrial fibrillation ablation: reaching the mainstream. Pacing Clin Electrophysiol. 2006 May;29(5):523-37. Review. — View Citation

Food and Drug Administration Guidance for Industry and FDA Staff: Clinical Study Designs for Percutaneous Catheter Ablation for Treatment of Atrial Fibrillation, January 9, 2004.

Fuster V, Rydén LE, Asinger RW, Cannom DS, Crijns HJ, Frye RL, Halperin JL, Kay GN, Klein WW, Lévy S, McNamara RL, Prystowsky EN, Wann LS, Wyse DG, Gibbons RJ, Antman EM, Alpert JS, Faxon DP, Fuster V, Gregoratos G, Hiratzka LF, Jacobs AK, Russell RO, Smith SC, Klein WW, Alonso-Garcia A, Blomström-Lundqvist C, De Backer G, Flather M, Hradec J, Oto A, Parkhomenko A, Silber S, Torbicki A; American College of Cardiology/American Heart Association/European Society of Cardiology Board. ACC/AHA/ESC 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 and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation): developed in Collaboration With the North American Society of Pacing and Electrophysiology. J Am Coll Cardiol. 2001 Oct;38(4):1231-66. — View Citation

Fuster V, Rydén 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, Halperin JL, 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, Tamargo JL, Zamorano JL; American College of Cardiology/American Heart Association Task Force on Practice Guidelines; European Society of Cardiology Committee for Practice Guidelines; European Heart Rhythm Association; Heart Rhythm Society. ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: 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): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation. 2006 Aug 15;114(7):e257-354. Erratum in: Circulation. 2007 Aug 7;116(6):e138. — View Citation

Gajewski J, Singer RB. Mortality in an insured population with atrial fibrillation. JAMA. 1981 Apr 17;245(15):1540-4. — View Citation

Haïssaguerre M, Sanders P, Hocini M, Hsu LF, Shah DC, Scavée C, Takahashi Y, Rotter M, Pasquié JL, Garrigue S, Clémenty J, Jaïs P. Changes in atrial fibrillation cycle length and inducibility during catheter ablation and their relation to outcome. Circulation. 2004 Jun 22;109(24):3007-13. Epub 2004 Jun 7. — View Citation

Hindricks G, Piorkowski C, Tanner H, Kobza R, Gerds-Li JH, Carbucicchio C, Kottkamp H. Perception of atrial fibrillation before and after radiofrequency catheter ablation: relevance of asymptomatic arrhythmia recurrence. Circulation. 2005 Jul 19;112(3):307-13. Epub 2005 Jul 11. — View Citation

Hornero F, Rodríguez I, Bueno M, Buendía J, Dalmau MJ, Canovas S, Gil O, Garcia R, Montero JA. Surgical ablation of permanent atrial fibrillation by means of maze radiofrequency: mid-term results. J Card Surg. 2004 Sep-Oct;19(5):383-8. — View Citation

Jaïs P, Hocini M, Sanders P, Hsu LF, Takahashi Y, Rotter M, Rostock T, Sacher F, Clementy J, Haissaguerre M. Long-term evaluation of atrial fibrillation ablation guided by noninducibility. Heart Rhythm. 2006 Feb;3(2):140-5. — View Citation

Kerr CR, Humphries KH, Talajic M, Klein GJ, Connolly SJ, Green M, Boone J, Sheldon R, Dorian P, Newman D. Progression to chronic atrial fibrillation after the initial diagnosis of paroxysmal atrial fibrillation: results from the Canadian Registry of Atrial Fibrillation. Am Heart J. 2005 Mar;149(3):489-96. — View Citation

Marrouche NF, Martin DO, Wazni O, Gillinov AM, Klein A, Bhargava M, Saad E, Bash D, Yamada H, Jaber W, Schweikert R, Tchou P, Abdul-Karim A, Saliba W, Natale A. Phased-array intracardiac echocardiography monitoring during pulmonary vein isolation in patients with atrial fibrillation: impact on outcome and complications. Circulation. 2003 Jun 3;107(21):2710-6. Epub 2003 May 19. — View Citation

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. — View Citation

Nilsson B, Chen X, Pehrson S, Køber L, Hilden J, Svendsen JH. Recurrence of pulmonary vein conduction and atrial fibrillation after pulmonary vein isolation for atrial fibrillation: a randomized trial of the ostial versus the extraostial ablation strategy. Am Heart J. 2006 Sep;152(3):537.e1-8. — View Citation

Oral H, Pappone C, Chugh A, Good E, Bogun F, Pelosi F Jr, Bates ER, Lehmann MH, Vicedomini G, Augello G, Agricola E, Sala S, Santinelli V, Morady F. Circumferential pulmonary-vein ablation for chronic atrial fibrillation. N Engl J Med. 2006 Mar 2;354(9):934-41. — View Citation

Packer DL, Asirvatham S, Munger TM. Progress in nonpharmacologic therapy of atrial fibrillation. J Cardiovasc Electrophysiol. 2003 Dec;14(12 Suppl):S296-309. Review. — View Citation

Pappone C, Rosanio S, Augello G, Gallus G, Vicedomini G, Mazzone P, Gulletta S, Gugliotta F, Pappone A, Santinelli V, Tortoriello V, Sala S, Zangrillo A, Crescenzi G, Benussi S, Alfieri O. Mortality, morbidity, and quality of life after circumferential pulmonary vein ablation for atrial fibrillation: outcomes from a controlled nonrandomized long-term study. J Am Coll Cardiol. 2003 Jul 16;42(2):185-97. — View Citation

PMA P020025 - Summary of Safety and Effectiveness Data: Boston Scientific Corporation Blazer II XP™ Cardiac Ablation Catheter, August 25, 2003.

PMA P030031 - Summary of Safety and Effectiveness Data: Biosense Webster Navistar™/Celsius™ThermoCool® Diagnostic/Ablation Deflectable Tip Catheters, November 5, 2004.

PMA P040042 - Summary of Safety and Effectiveness Data: Irvine Biomedical, Inc. IBI Therapy™ Dual 8™ Ablation Catheter, November 18, 2005.

Rotter M, Takahashi Y, Sanders P, Haïssaguerre M, Jaïs P, Hsu LF, Sacher F, Pasquié JL, Clementy J, Hocini M. Reduction of fluoroscopy exposure and procedure duration during ablation of atrial fibrillation using a novel anatomical navigation system. Eur Heart J. 2005 Jul;26(14):1415-21. Epub 2005 Mar 1. — View Citation

Saad EB, Cole CR, Marrouche NF, Dresing TJ, Perez-Lugones A, Saliba WI, Schweikert RA, Klein A, Rodriguez L, Grimm R, Tchou P, Natale A. Use of intracardiac echocardiography for prediction of chronic pulmonary vein stenosis after ablation of atrial fibrillation. J Cardiovasc Electrophysiol. 2002 Oct;13(10):986-9. — View Citation

Saad EB, Rossillo A, Saad CP, Martin DO, Bhargava M, Erciyes D, Bash D, Williams-Andrews M, Beheiry S, Marrouche NF, Adams J, Pisanò E, Fanelli R, Potenza D, Raviele A, Bonso A, Themistoclakis S, Brachmann J, Saliba WI, Schweikert RA, Natale A. Pulmonary vein stenosis after radiofrequency ablation of atrial fibrillation: functional characterization, evolution, and influence of the ablation strategy. Circulation. 2003 Dec 23;108(25):3102-7. Epub 2003 Nov 17. — View Citation

Sanders P, Nalliah CJ, Dubois R, Takahashi Y, Hocini M, Rotter M, Rostock T, Sacher F, Hsu LF, Jönsson A, O'Neill MD, Jaïs P, Haïssaguerre M. Frequency mapping of the pulmonary veins in paroxysmal versus permanent atrial fibrillation. J Cardiovasc Electrophysiol. 2006 Sep;17(9):965-72. — View Citation

Scardi S, Mazzone C, Pandullo C, Goldstein D, Poletti A, Humar F. Lone atrial fibrillation: prognostic differences between paroxysmal and chronic forms after 10 years of follow-up. Am Heart J. 1999 Apr;137(4 Pt 1):686-91. — View Citation

Vasamreddy CR, Dalal D, Dong J, Cheng A, Spragg D, Lamiy SZ, Meininger G, Henrikson CA, Marine JE, Berger R, Calkins H. Symptomatic and asymptomatic atrial fibrillation in patients undergoing radiofrequency catheter ablation. J Cardiovasc Electrophysiol. 2006 Feb;17(2):134-9. — View Citation

Vasamreddy CR, Dalal D, Eldadah Z, Dickfeld T, Jayam VK, Henrickson C, Meininger G, Dong J, Lickfett L, Berger R, Calkins H. Safety and efficacy of circumferential pulmonary vein catheter ablation of atrial fibrillation. Heart Rhythm. 2005 Jan;2(1):42-8. — View Citation

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. — View Citation

* Note: There are 34 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Chronic Effectiveness	The chronic efficacy endpoint was a treatment success/failure measure for each subject computed at 6 months. Treatment success included: A 90% reduction in clinically significant atrial fibrillation from baseline to the 6 month time point based on a Holter recording. Clinically significant atrial fibrillation was defined as sustained atrial fibrillation lasting more than 10 minutes.; The subject was off all antiarrhythmic drugs at 6 months (Ablation Management arm only); The Investigator judged all procedures to be acutely successful (Ablation Management arm only).	6 months
Primary	Acute Safety	The primary endpoint for acute safety was a success/failure variable calculated for each subject in Ablation Management at the 7 day post-procedure time point. Any subject with at least one adverse event adjudicated by the Data Safety Monitoring Board as both serious and either probably or definitely procedure and/or device-related occurring within 7 days of the ablation procedure was considered an acute safety failure, regardless of whether the event occurred following the index or retreatment ablation procedure.	7 days
Primary	Chronic Safety	The primary endpoint for chronic safety was a success/failure variable calculated for each subject at 6 months. Any subject that had at least one adverse event that met designated seriousness and relatedness criteria for the particular treatment group as adjudicated by the Data Safety Monitoring Board was considered a chronic safety failure. Adverse events in Ablation Management that were acute (=7 days) were not included in the chronic safety primary endpoint. Given the disparity in the length of time at risk between treatment arms,the Chronic Safety endpoint was not statistically powered.	6 months
Secondary	Acute Efficacy	A treatment success/failure up to the conclusion of the procedure for each subject in Ablation Management. A subject was considered successfully treated if the following were true: Medtronic ablation catheters were used to achieve procedure success.; All accessible pulmonary veins were isolated.; At least 50% reduction of complex fractionated atrial electrograms mapped and ablated with Medtronic ablation catheters.; Sinus rhythm was achieved upon leaving the electrophysiology lab (±cardioversion).	Procedure conclusion
Secondary	Improvement of Left Atrial Size at 6 Months Compared to Baseline.	Left atrial diameter (LAD), as measured by transthoracic echocardiogram (TTE) looking at the longitudinal long axis at baseline and at the 6 month follow-up visit in both the Ablation and Medical Management arms.	6 months
Secondary	Improvement of Left Ventricular Ejection Fraction at 6 Months Compared to Baseline.	Left ventricular ejection fraction (LVEF), as measured by transthoracic echocardiogram at baseline and 6 months in both the Ablation and Medical Management arms.	6 months
Secondary	Improvement in Atrial Fibrillation (AF) Symptom Severity Scores Over 6 Months Compared to Baseline.	The severity of subject's atrial fibrillation related symptoms on a scale from 1 (no symptoms) to 5 (most severe). The symptoms included palpitations, fatigue, shortness of breath, lightheadedness or dizziness, and lack of energy during exertion or exercise. The scores were tabulated at the 1, 3 and 6 month follow-up visits. Scores could range from 5 to 25, indicating a spectrum of subject status from asymptomatic to severely symptomatic.	6 months
Secondary	Improved Quality of Life Over 6 Months Compared to Baseline.	The SF-36 questionnaire was administered to subjects at baseline, 1, 3 and 6 month visits. The SF-36 is a multi-purpose, short-form health survey with only 36 questions. It yields an 8-scale profile of functional health and well-being scores as well as psychometrically-based Physical Component Score and Mental Component Score. The possible range for Physical Component Score and Mental Component Score is 0 to 100. The higher score, the better quality of life.	6 months

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