Tailored Treatment of Permanent Atrial Fibrillation (TTOP-AF)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Medtronic Atrial Fibrillation Solutions
ClinicalTrials.gov Identifier:
NCT00514735
First received: August 8, 2007
Last updated: April 11, 2012
Last verified: April 2012
  Purpose

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.


Condition Intervention Phase
Atrial Fibrillation
Procedure: Medtronic Cardiac Ablation System
Drug: Class I or III Antiarrhythmic Medications
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Tailored Treatment of Permanent Atrial Fibrillation - TTOP-AF

Resource links provided by NLM:


Further study details as provided by Medtronic Atrial Fibrillation Solutions:

Primary Outcome Measures:
  • Chronic Effectiveness [ Time Frame: 6 months ] [ Designated as safety issue: No ]

    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).

  • Acute Safety [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    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.

  • Chronic Safety [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Acute Efficacy [ Time Frame: Procedure conclusion ] [ Designated as safety issue: No ]

    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).

  • Improvement of Left Atrial Size at 6 Months Compared to Baseline. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.

  • Improvement of Left Ventricular Ejection Fraction at 6 Months Compared to Baseline. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Left ventricular ejection fraction (LVEF), as measured by transthoracic echocardiogram at baseline and 6 months in both the Ablation and Medical Management arms.

  • Improvement in Atrial Fibrillation (AF) Symptom Severity Scores Over 6 Months Compared to Baseline. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.

  • Improved Quality of Life Over 6 Months Compared to Baseline. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.


Enrollment: 210
Study Start Date: May 2007
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Ablation Management
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.
Active Comparator: 2
Medical Management
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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00514735

  Hide Study Locations
Locations
United States, Arizona
Arizona Arrhythmia Research Center
Scottsdale, Arizona, United States, 85251
United States, California
UCLA Cardiac Arrhythmia Center
Los Angeles, California, United States, 90095
United States, Florida
Mayo Clinic Jacksonville
Jacksonville, Florida, United States, 32224
United States, Georgia
Emory Crawford Long Hospital
Atlanta, Georgia, United States, 30308
Piedmont Hospital
Atlanta, Georgia, United States, 30309
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Indiana
Krannert Institute of Cardiology
Indianapolis, Indiana, United States, 46202
United States, Iowa
Genesis Medical Center
Davenport, Iowa, United States, 52803
Iowa Heart Center
Des Moines, Iowa, United States, 50309
United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
Washington Adventist Hospital
Takoma Park, Maryland, United States, 20912
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital Cardiac Arrhythmia
Boston, Massachusetts, United States, 02114
Lahey Clinic
Burlington, Massachusetts, United States, 01805
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Spectrum Health Research Department
Grand Rapids, Michigan, United States, 49503
United States, New York
University of Rochester
Rochester, New York, United States, 14642
United States, North Carolina
Wake Forest University
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
The Ohio State University
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Consultants in Cardiovascular Diseases
Erie, Pennsylvania, United States, 16502
United States, Texas
Austin Heart
Austin, Texas, United States, 78756
Texas Heart Institute at St. Luke's Episcopal
Houston, Texas, United States, 77030
United States, Virginia
Sentara Cardiovascular Research Institute
Norfolk, Virginia, United States, 23507
Netherlands
St. Antonius Ziekenhuis
Nieuwegein, Netherlands
Sponsors and Collaborators
Medtronic Atrial Fibrillation Solutions
  More Information

Additional Information:
Publications:
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.
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. No abstract available. Erratum in: Circulation. 2007 Aug 7;116(6):e138.

Responsible Party: Medtronic Atrial Fibrillation Solutions
ClinicalTrials.gov Identifier: NCT00514735     History of Changes
Other Study ID Numbers: AFI-30
Study First Received: August 8, 2007
Results First Received: January 25, 2012
Last Updated: April 11, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Medtronic Atrial Fibrillation Solutions:
atrial fibrillation

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

ClinicalTrials.gov processed this record on July 20, 2014