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
Results First Received: January 25, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Atrial Fibrillation
Interventions: Procedure: Medtronic Cardiac Ablation System
Drug: Class I or III Antiarrhythmic Medications

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The first subject was enrolled on November 28, 2007. The very last ablation procedure was a retreatment ablation procedure for a Medical Management Crossover subject that occurred on May 7, 2010 with the final follow-up on November 1, 2010.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

32 subjects signed Informed Consent forms but withdrew from the study prior to randomization.

  • 24 failed to meet inclusion/exclusion criteria
  • 6 elected to withdraw
  • 1 subject was withdrawn by the Sponsor after being consented.
  • 1 subject was withdrawn as screening was incomplete prior to closing enrollment for the study

Reporting Groups
  Description
Ablation Management Pre- and post- procedure anticoagulation was managed according to the preference of the investigator. Left atrial access was obtained by a single transseptal puncture. No ablations were to occur until the activated clotting time reached 300 seconds, which was to be maintained for the duration of the ablation. During the index ablation procedure, investigators were required to use all 3 investigational catheters. Cardioversion could be used to restore sinus rhythm if needed. If there was a recurrence of atrial fibrillation, a repeat ablation procedure could be performed any time during the follow-up period. With a retreatment, the follow-up clock was restarted. Subjects were seen pre-discharge and at in-clinic follow-up visits at 1, 3, and 6 months.
Medical Management Medical Management subjects were prescribed Class I or III antiarrhythmic drugs. Changes in dosing, antiarrhythmic drugs or combinations of antiarrhythmic drugs were allowed. Direct current (DC) cardioversions were also allowed at the discretion of the investigator. Anticoagulation was to be maintained at an International Normalized Ratio greater than 2. Subjects were seen at in-clinic follow-up visits at 1, 3, and 6 months. Subjects who demonstrated chronic treatment failure while under drug therapy could cross over, and receive an ablation as early as 4 months post randomization.

Participant Flow:   Overall Study
    Ablation Management     Medical Management  
STARTED     138     72  
COMPLETED     124     66  
NOT COMPLETED     14     6  
Withdrawal by Subject                 13                 5  
Death                 1                 0  
Lost to Follow-up                 0                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Ablation Management Pre- and post- procedure anticoagulation was managed according to the preference of the investigator. Left atrial access was obtained by a single transseptal puncture. No ablations were to occur until the activated clotting time reached 300 seconds, which was to be maintained for the duration of the ablation. During the index ablation procedure, investigators were required to use all 3 investigational catheters. Cardioversion could be used to restore sinus rhythm if needed. If there was a recurrence of atrial fibrillation, a repeat ablation procedure could be performed any time during the follow-up period. With a retreatment, the follow-up clock was restarted. Subjects were seen pre-discharge and at in-clinic follow-up visits at 1, 3, and 6 months.
Medical Management Medical Management subjects were prescribed Class I or III antiarrhythmic drugs. Changes in dosing, antiarrhythmic drugs or combinations of antiarrhythmic drugs were allowed. Direct current (DC) cardioversions were also allowed at the discretion of the investigator. Anticoagulation was to be maintained at an International Normalized Ratio greater than 2. Subjects were seen at in-clinic follow-up visits at 1, 3, and 6 months. Subjects who demonstrated chronic treatment failure while under drug therapy could cross over, and receive an ablation as early as 4 months post randomization.
Total Total of all reporting groups

Baseline Measures
    Ablation Management     Medical Management     Total  
Number of Participants  
[units: participants]
  138     72     210  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     93     43     136  
>=65 years     45     29     74  
Age  
[units: years]
Mean ± Standard Deviation
  59.6  ± 8.3     60.7  ± 8.9     60.0  ± 8.5  
Gender  
[units: participants]
     
Female     23     12     35  
Male     115     60     175  
Region of Enrollment  
[units: participants]
     
United States     126     65     191  
Netherlands     12     7     19  
Number of DC cardioversions in past 4 years [1]
[units: cardioversions]
Mean ± Standard Deviation
  2.0  ± 1.1     2.4  ± 3.5     2.1  ± 2.2  
Number of previously failed AADs per subject  
[units: antiarrhythmic drugs]
Mean ± Standard Deviation
  1.4  ± 0.6     1.1  ± 0.4     1.3  ± 0.6  
Left Atrial Diameter  
[units: centimeters]
Mean ± Standard Deviation
  4.5  ± 0.5     4.6  ± 0.5     4.6  ± 0.5  
Left Ventricular Ejection Fraction  
[units: percent]
Mean ± Standard Deviation
  54.7  ± 7.1     54.9  ± 6.7     54.7  ± 7.0  
[1] Number of DC cardioversions in past 4 years per subject



  Outcome Measures
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1.  Primary:   Chronic Effectiveness   [ Time Frame: 6 months ]

2.  Primary:   Acute Safety   [ Time Frame: 7 days ]

3.  Primary:   Chronic Safety   [ Time Frame: 6 months ]

4.  Secondary:   Acute Efficacy   [ Time Frame: Procedure conclusion ]

5.  Secondary:   Improvement of Left Atrial Size at 6 Months Compared to Baseline.   [ Time Frame: 6 months ]

6.  Secondary:   Improvement of Left Ventricular Ejection Fraction at 6 Months Compared to Baseline.   [ Time Frame: 6 months ]

7.  Secondary:   Improvement in Atrial Fibrillation (AF) Symptom Severity Scores Over 6 Months Compared to Baseline.   [ Time Frame: 6 months ]

8.  Secondary:   Improved Quality of Life Over 6 Months Compared to Baseline.   [ Time Frame: 6 months ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
- The study population was mostly Caucasian men.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Linda Nelson, Director of Clinical Research
Organization: Medtronic
phone: 763-526-2891
e-mail: linda.k.nelson@medtronic.com


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