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Atrial FibrillationPhase 3TTOP-AFNCT00514735

Tailored Treatment of Permanent Atrial Fibrillation

A Phase 3 study testing Medtronic Cardiac Ablation System and Class I or III Antiarrhythmic Medications in people with Atrial Fibrillation, run by Medtronic Cardiac Rhythm and Heart Failure at 24 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Atrial Fibrillation
What is being tested?
Medtronic Cardiac Ablation System and Class I or III Antiarrhythmic Medications
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
210 participants
Where
24 sitesin 2 countries
Study dates
May 2007to Nov 2010
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 24Show fewer
  • 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

Trial locations and contacts

24 sites in 2 countries.

24 sites in 2 countries

United States23 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Emory Crawford Long Hospital

    Atlanta, Georgia, 30308

  • Piedmont Hospital

    Atlanta, Georgia, 30309

  • Austin Heart

    Austin, Texas, 78756

  • Johns Hopkins Hospital

    Baltimore, Maryland, 21287

  • Massachusetts General Hospital Cardiac Arrhythmia

    Boston, Massachusetts, 02114

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Lahey Clinic

    Burlington, Massachusetts, 01805

  • University of Chicago

    Chicago, Illinois, 60637

  • The Ohio State University

    Columbus, Ohio, 43210

  • Genesis Medical Center

    Davenport, Iowa, 52803

  • Iowa Heart Center

    Des Moines, Iowa, 50309

  • Consultants in Cardiovascular Diseases

    Erie, Pennsylvania, 16502

  • Spectrum Health Research Department

    Grand Rapids, Michigan, 49503

  • Texas Heart Institute at St. Luke's Episcopal

    Houston, Texas, 77030

  • Krannert Institute of Cardiology

    Indianapolis, Indiana, 46202

  • Mayo Clinic Jacksonville

    Jacksonville, Florida, 32224

  • UCLA Cardiac Arrhythmia Center

    Los Angeles, California, 90095

  • Sentara Cardiovascular Research Institute

    Norfolk, Virginia, 23507

  • University of Rochester

    Rochester, New York, 14642

  • Arizona Arrhythmia Research Center

    Scottsdale, Arizona, 85251

  • Washington Adventist Hospital

    Takoma Park, Maryland, 20912

  • Wake Forest University

    Winston-Salem, North Carolina, 27157

Other trials in United States

Netherlands1 site

  • St. Antonius Ziekenhuis

    Nieuwegein

Other trials in Netherlands

About this study

Official title: Tailored Treatment of Permanent Atrial Fibrillation - TTOP-AF

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.

Being tested
Medtronic Cardiac Ablation System, Class I or III Antiarrhythmic Medications
Keywords
atrial fibrillation
Medical subject headings
Atrial Fibrillation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Medtronic Cardiac Ablation SystemProcedure or surgery

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

  • Class I or III Antiarrhythmic MedicationsDrug

    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.

Study groups in NCT00514735
Study groupRoleWhat they receive
1ExperimentalAblation Management
Receives: Procedure: Medtronic Cardiac Ablation System
2Active comparatorMedical Management
Receives: Drug: Class I or III Antiarrhythmic Medications

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Chronic Effectiveness

    The chronic efficacy endpoint was a treatment success/failure measure for each subject computed at 6 months. Treatment success included:

    1. 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.
    2. The subject was off all antiarrhythmic drugs at 6 months (Ablation Management arm only)
    3. The Investigator judged all procedures to be acutely successful (Ablation Management arm only).

    Measured: 6 months

  2. 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.

    Measured: 7 days

  3. 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.

    Measured: 6 months

Secondary outcomes (5)

  1. 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).

    Measured: Procedure conclusion

  2. 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.

    Measured: 6 months

  3. 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.

    Measured: 6 months

  4. 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.

    Measured: 6 months

  5. 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.

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Aug 2007 (estimated)
  2. Study startMay 2007
  3. Primary completionNov 2010
  4. Study completionNov 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
210 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00514735
Sponsor's protocol ID
AFI-30
Acronym
TTOP-AF
Status last verified
Sep 2018
First submitted
8 Aug 2007
Last updated
16 Oct 2018
Data monitoring committee
Yes

Publications

  • Fuster V, Ryden LE, Asinger RW, Cannom DS, Crijns HJ, Frye RL, Halperin JL, Kay GN, Klein WW, Levy 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, Blomstrom-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. doi: 10.1016/s0735-1097(01)01587-x. No abstract available.

    PubMed 11583910

  • 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, 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. doi: 10.1161/CIRCULATIONAHA.106.177292. No abstract available.

    PubMed 16908781

  • 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. doi: 10.1016/j.jtcvs.2005.01.009.

    PubMed 16077418

  • 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. doi: 10.1161/01.cir.0000048146.81336.1d.

    PubMed 12591754

  • 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. doi: 10.1111/j.1540-8167.2005.40680.x.

    PubMed 16101625

  • 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.

  • 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. doi: 10.1161/CIRCULATIONAHA.104.526301.

    PubMed 16159816

  • 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. doi: 10.1111/j.1540-8159.2006.00388.x.

    PubMed 16689850

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

    PubMed 7206163

  • de Lima GG, Kalil RA, Leiria TL, Hatem DM, Kruse CL, Abrahao 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. doi: 10.1016/j.athoracsur.2003.11.018.

    PubMed 15172273

  • 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. doi: 10.1161/CIRCULATIONAHA.104.518837. Epub 2005 Jul 11.

    PubMed 16009793

  • Hornero F, Rodriguez I, Bueno M, Buendia 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. doi: 10.1111/j.0886-0440.2004.04077.x.

    PubMed 15383047

  • 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. doi: 10.1016/j.ahj.2004.09.053.

    PubMed 15864238

  • 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. doi: 10.1161/01.CIR.0000070541.83326.15. Epub 2003 May 19.

    PubMed 12756153

  • 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. doi: 10.1016/j.jacc.2003.12.054.

    PubMed 15172410

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Medtronic Cardiac Ablation System and Class I or III Antiarrhythmic Medications in people with Atrial Fibrillation, run by Medtronic Cardiac Rhythm and Heart Failure at 24 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in United States, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 May 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Chronic Effectiveness (time frame: 6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00514735, which also lists 34 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2018.

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