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First Line Radiofrequency Ablation Versus Antiarrhythmic Drugs for Persistent Atrial Fibrillation Treatment (RAAFT-3)

Sponsor
University of Pennsylvania (Other)
Overall Status
Recruiting
CT.gov ID
NCT04037397
Collaborator
Biosense Webster, Inc. (Industry), Texas Cardiac Arrhythmia Research Foundation (Other)
120
Enrollment
4
Locations
2
Arms
65.2
Anticipated Duration (Months)
30
Patients Per Site
0.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if catheter-based atrial fibrillation (AF) ablation is superior to treatment with antiarrhythmic drugs as a first-line therapy for symptomatic persistent AF.

Condition or Disease Intervention/Treatment Phase
  • Drug: Anti Arrhythmics
  • Procedure: Pulmonary Vein Isolation performed by Radio Frequency Catheter Ablation
 Phase 3

Detailed Description

The burden of atrial fibrillation (AF) on Western countries healthcare systems is steadily increasing, with over 2 million Americans and 4 million Europeans affected by this condition. It is by far the most common sustained arrhythmia encountered in clinical practice, with a striking impact on morbidity and mortality. Achieving a definite cure is highly desirable, as this would have profound social and economic implication. In patients with drug-refractory paroxysmal AF, multiple clinical trials have established the superiority of catheter ablation over further antiarrhythmic drug (AAD) therapy for the long-term maintenance of sinus rhythm, to improve quality of life, and reduce hospitalizations. Recent randomized controlled trials have also demonstrated a beneficial role of catheter ablation as a first-line therapy in patients with paroxysmal AF, with significantly better arrhythmia control and improved quality of life compared to AAD therapy. Patients with symptomatic persistent AF represent a more challenging group to treat, given the overall lower success rate of catheter ablation procedures in this group of patients. Pharmacologic rhythm-control strategies are also less effective in persistent AF, with a substantially increased economic burden given the repeat admissions for electrical cardioversions and AAD initiation/titration. In patients with symptomatic persistent AF who have already failed AADs, catheter ablation has been shown superior to further AAD therapy for sinus rhythm restoration in a recent randomized controlled trial. However, the value of an upstream adoption of catheter ablation for the treatment of symptomatic persistent AF (i.e., before a trial with AADs) is unknown. The purpose of the third Radiofrequency Ablation vs Antiarrhythmic Drugs for Atrial Fibrillation Treatment (RAAFT-3) trial is to determine whether catheter ablation is superior to AAD as a first-line therapy in patients with persistent AF who had not been exposed to antiarrhythmic treatment.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
120 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
120 patients will be randomized in a 2:1 fashion (80 in the RFCA arm; 40 in the AADs arm)120 patients will be randomized in a 2:1 fashion (80 in the RFCA arm; 40 in the AADs arm)
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
First Line Radiofrequency Ablation Versus Antiarrhythmic Drugs for Persistent Atrial Fibrillation Treatment
Actual Study Start Date :
Sep 24, 2019
Anticipated Primary Completion Date :
Oct 1, 2023
Anticipated Study Completion Date :
Mar 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Antiarrhythmic Medications

Patients randomized to the antiarrhythmic drug group are administered medications approved for treatment of AF by the regulatory bodies of each participating country. The selection of antiarrhythmic drugs and dosages is left to the discretion of the investigator, and will follow the AHA/ACC/HRS general guidelines

Drug: Anti Arrhythmics
Propafenone or Flecanide or Sotalol or Dofetilide or Dronedarone or Amiodarone. The subject must first fail a Class 1C or III drug prior to starting Amiodarone
Active Comparator: Radio Frequency Catheter Ablation

Patients randomized to radiofrequency catheter ablation will undergo isolation of the pulmonary veins with confirmation of entrance block into each vein. The CARTO TM(Biosense Webster, CA) system will be used to reconstruct the atrial geometry and assist for mapping and ablation. Ablation will be performed using approved ablation devices (Biosense Webster, CA).

Procedure: Pulmonary Vein Isolation performed by Radio Frequency Catheter Ablation
Approved Biosense Webster Inc. catheter devices should be used to perform RFCA. Ablation will be done to achieve entrance block into all pulmonary veins

Outcome Measures

Primary Outcome Measures

  1. Recurrence of symptomatic Atrial Fibrillation [18 Months]

    Recurrence (post 90- day blanking period) of symptomatic or asymptomatic AF, atrial flutter, or atrial tachycardia lasting more than 30 seconds documented by the pre-defined ECG monitoring is the primary efficacy outcome. Any episodes occurring during the 90-day blanking period are not considered as recurrences

Secondary Outcome Measures

  1. Time to AF recurrence [18 Months]

    Time to first documented recurrence of AF, atrial flutter, and atrial tachycardia episodes

  2. Repeat Episodes of AF [18 Months]

    Repeated episodes (≥2) of symptomatic or asymptomatic AF, atrial flutter, and atrial tachycardia episodes

  3. AF/AT Burden [18 Months]

    Cumulative AF/AT burden (defined as percentage of time in AF/AT during follow-up)

  4. CV Hospitalizations [18 Months]

    Hospitalization for cardiovascular and non-cardiovascular causes during follow-up

  5. Quality of Life Questionnaire [18 Months]

    Quality of life at the 1-year follow-up by SF-36

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

Eligible patients have a history of persistent AF with at least 2 episodes in the 9 months prior to enrollment. Persistent AF is defined according to 2014 AHA/ACC/HRS guidelines as continuous AF that is sustained for more than 7 days.Patients are enrolled if they are:

  1. Older than 18.

  2. Symptomatic with persistent AF.

  3. Experienced at least one AF episode that was documented by surface ECG, 6 months before randomization.

Exclusion Criteria:

  1. Documented LVEF <40%.

  2. Documented left atrial diameter >/=6cm.

  3. Moderate to severe LVH (LV wall thickness >1.5cm).

  4. Documented severe valvular disease (aortic stenosis, mitral regurgitation, tricuspid regurgitation or presence of mechanical cardiac valves), active coronary artery disease (defined as the presence of >70% stenosis of coronary arteries or documentation of active myocardial ischemia), recent (within 6 months) CABG.

  5. Untreated hypothyroidism or hyperthyroidism. Patients who are euthyroid on thyroid hormone replacement therapy are acceptable.

  6. Contraindication for the use of all antiarrhythmic drugs including sotalol, dofetilide, amiodarone 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). [Note: Participants will not be excluded if they are able to take any single or combination of drugs without contraindications]

  7. Previous left heart ablation procedure, either by surgery or by percutaneous catheter, for atrial fibrillation.

  8. Current enrollment in another investigational drug or device study.

  9. 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.

  10. Absolute contra-indication to the use of heparin and or oral anticoagulation.

  11. Increase risk of bleeding, current peptic ulceration, proliferative diabetic retinopathy, history of severe systemic bleeding, or other history of bleeding diathesis or coagulopathy.

  12. Severe pulmonary disease e.g. restrictive pulmonary disease, chronic obstructive disease (COPD).

  13. Documented intra-atrial thrombus, tumor, or another abnormality, which precludes left atrial catheter ablation.

  14. Previous use of an antiarrhythmic drug, including amiodarone, propafenone, flecainide, sotalol, quinidine, dofetilide, dronedarone (see below for specifications: Antiarrhythmic Drug Group).

  15. Women with a positive pregnancy test.

  16. Evidence of active cardiac or systemic infection.

  17. Medical condition limiting expected survival to less than one year.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Montefiore Medical Center Bronx New York United States 10461
2 MetroHealth Cleveland Ohio United States 44109
3 Penn Presbyterian Medical Center Philadelphia Pennsylvania United States 19104
4 University of Pennsylvania Philadelphia Pennsylvania United States 19104

Sponsors and Collaborators

  • University of Pennsylvania
  • Biosense Webster, Inc.
  • Texas Cardiac Arrhythmia Research Foundation

Investigators

  • Principal Investigator: Andrea Natale, MD, Texas Cardiac Arrhythmia Research Foundation

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT04037397
Other Study ID Numbers:
  • 829475
First Posted:
Jul 30, 2019
Last Update Posted:
May 18, 2022
Last Verified:
May 1, 2022
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
Yes
Keywords provided by University of Pennsylvania
Pulmonary Vein Isolation
Additional relevant MeSH terms:
Atrial Fibrillation
Anti-Arrhythmia Agents

Study Results

No Results Posted as of May 18, 2022