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

October 17, 2023 updated by: University of Pennsylvania

First Line Radiofrequency Ablation Versus Antiarrhythmic Drugs for Persistent Atrial Fibrillation Treatment

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

120

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States, 84724
        • University of Arizona
    • New York
      • Bronx, New York, United States, 10461
        • Montefiore Medical Center
    • Ohio
      • Cleveland, Ohio, United States, 44109
        • MetroHealth
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Penn Presbyterian Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recurrence of symptomatic Atrial Fibrillation
Time Frame: 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
18 Months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to AF recurrence
Time Frame: 18 Months
Time to first documented recurrence of AF, atrial flutter, and atrial tachycardia episodes
18 Months
Repeat Episodes of AF
Time Frame: 18 Months
Repeated episodes (≥2) of symptomatic or asymptomatic AF, atrial flutter, and atrial tachycardia episodes
18 Months
AF/AT Burden
Time Frame: 18 Months
Cumulative AF/AT burden (defined as percentage of time in AF/AT during follow-up)
18 Months
CV Hospitalizations
Time Frame: 18 Months
Hospitalization for cardiovascular and non-cardiovascular causes during follow-up
18 Months
Quality of Life Questionnaire
Time Frame: 18 Months
Quality of life at the 1-year follow-up by SF-36
18 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pennsylvania

Collaborators

Biosense Webster, Inc.
Texas Cardiac Arrhythmia Research Foundation

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 24, 2019

Primary Completion (Estimated)

October 1, 2024

Study Completion (Estimated)

March 1, 2025

Study Registration Dates

First Submitted

July 25, 2019

First Submitted That Met QC Criteria

July 29, 2019

First Posted (Actual)

July 30, 2019

Study Record Updates

Last Update Posted (Actual)

October 18, 2023

Last Update Submitted That Met QC Criteria

October 17, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 829475

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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