RAFT-AF: Rhythm Control - Catheter Ablation With or Without Anti-arrhythmic Drug Control of Maintaining Sinus Rhythm Versus Rate Control With Medical Therapy and/or Atrio-ventricular Junction Ablation and Pacemaker Treatment for Atrial Fibrillation

Sponsor
Ottawa Heart Institute Research Corporation (Other)
Overall Status
Completed
CT.gov ID
NCT01420393
Collaborator
Canadian Institutes of Health Research (CIHR) (Other)
411
Enrollment
21
Locations
2
Arms
117
Duration (Months)
19.6
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Atrial fibrillation and heart failure are two common heart conditions that are associated with an increase in death and suffering. When both of these two conditions occur in a patient the patient's prognosis is poor. These patients have poor life quality and are frequently admitted to the hospital. The treatment of atrial fibrillation in heart failure patients is extremely challenging. Two options for managing the atrial fibrillation are permitting the atrial fibrillation to continue but controlling the heart rate, or to convert the atrial fibrillation rhythm back to normal and try to maintain the heart in sinus rhythm. Until now, the method to keep the patient in normal sinus rhythm is with antiarrhythmic drugs. Studies using antiarrhythmic drugs to control the rhythm failed to show any survival benefit when compared with permitting the patient to be in atrial fibrillation. In the last few years, new development in techniques and technologies now enable catheter ablation (cauterization of tissue in the heart with a catheter) to be a successful treatment in abolishing atrial fibrillation and that this approach is better than antiarrhythmic drug to control the rhythm. However, there has not been any long-term study to determine whether catheter ablation to abolish atrial fibrillation in heart failure patients would reduce mortality or admissions for heart failure.

This study is to compare the effect of catheter ablation-based atrial fibrillation rhythm control to rate control in patients with heart failure and high burden atrial fibrillation on the composite endpoint of all-cause mortality and heart failure events defined as an admission to a healthcare facility for > 24 hours or clinically significant worsening heart failure leading to an intervention (defined as treatment in an emergency department, a same-day access clinic, or an infusion centre) or unscheduled visits to a healthcare provider for administration of an intravenous diuretic and an increase in chronic heart failure therapy. This study may have a dramatic impact on the way the investigators manage these patients with atrial fibrillation and heart failure and may improve the outlook and well being of these patients.

Condition or DiseaseIntervention/TreatmentPhase
  • Procedure: Rhythm control
  • Other: Rate Control
N/A

Detailed Description

Substudy_ In a subset of patients, following informed consent, additional data collection will include annual NT-proBNP/BNP measurements, Echocardiogram baseline and annually and 14 Day ECG Continuous Monitoring at six month intervals.

Study Design

Study Type:
Interventional
Actual Enrollment :
411 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized Ablation-based Atrial Fibrillation Rhythm Control Versus Rate Control Trial in Patients With Heart Failure and High Burden Atrial Fibrillation
Study Start Date :
Sep 1, 2011
Actual Primary Completion Date :
May 1, 2021
Actual Study Completion Date :
Jun 1, 2021

Arms and Interventions

ArmIntervention/Treatment
Active Comparator: Rhythm Control

Patients randomized to catheter ablation-based AF rhythm control group will receive optimal Heart Failure therapy and one or more aggressive catheter ablation, which include PV antral ablation and LA substrate ablation with or without adjunctive antiarrhythmic drug.

Procedure: Rhythm control
Patients randomized to catheter ablation-based AF rhythm control group will receive optimal HF therapy and one or more aggressive catheter ablation, which include PV antral ablation and LA substrate ablation with or without adjunctive antiarrhythmic drug
Other Names:
  • Catheter ablation
  • Active Comparator: Rate Control

    Patients in the rate control group will receive optimal Heart Failure therapy and rate control measures to achieve a resting HR < 80 bpm and 6-minute walk HR < 110 bpm.

    Other: Rate Control
    Patients in the rate control group will receive optimal HF therapy and rate control measures to achieve a resting HR < 80 bpm and 6-minute walk HR < 110 bpm.
    Other Names:
  • Standard medical therapy
  • Outcome Measures

    Primary Outcome Measures

    1. Composite of all-cause mortality and heart failure events [Baseline to a minimum of 24 months]

      Heart failure event defined as an admission to a healthcare facility for > 24 hours or clinically significant worsening heart failure leading to an intervention (defined as treatment in an emergency department, a same-day access clinic, or an infusion centre) or unscheduled visits to a healthcare provider for administration of an intravenous diuretic as accepted by FDA and an increase in chronic heart failure therapy

    Secondary Outcome Measures

    1. All-cause mortality [Baseline to a minimum of 24 months]

      All-cause mortality

    2. Heart Failure events [Baseline to a minimum of 24 months]

      Heart failure event defined as an admission to a healthcare facility for > 24 hours or clinically significant worsening heart failure leading to an intervention (defined as treatment in an emergency department, a same-day access clinic, or an infusion centre) or unscheduled visits to a healthcare provider for administration of an intravenous diuretic as accepted by FDA and an increase in chronic heart failure therapy

    3. Health related QoL [Baseline to a minimum of 24 months]

      Minnesota Living with Heart Failure

    4. Health related QoL [Baseline to a minimum of 24 months]

      EuroQol- 5 Dimension

    5. Health related QoL [Baseline to a minimum of 24 months]

      Atrial Fibrillation Effect on Quality-of-life

    6. Exercise capacity [Baseline to a minimum of 24 months]

      as determined by 6 Minute Hall walk distance

    7. NT-proBNP/BNP at 1 year and at 2 year follow-up [Baseline to a minimum of 24 months]

      NT-proBNP/BNP

    8. All-cause mortality and heart failure events in patients with HF, impaired (LVEF≤45%) LV function and high burden AF [Baseline to a minimum of 24 months]

    9. All-cause mortality and heart failure events in patients with HF, preserved (LVEF > 45%) LV function and high burden AF [Baseline to a minimum of 24 months]

    10. Health economics [Baseline to a minimum of 24 months]

      Cost economics

    Other Outcome Measures

    1. LV function and remodeling (LVESVi) at 1 year and 2 year follow-up [Baseline to a minimum of 24 months]

      Echocardiogram measure LVESVi

    2. AF Burden at 1 year and 2 year follow-up [Baseline to a minimum of 24 months]

      14 Day Continuous ECG monitoring

    3. Total number of heart failure events [Baseline to a minimum of 24 months]

      Heart failure event defined as an admission to a healthcare facility for > 24 hours or clinically significant worsening heart failure leading to an intervention (defined as treatment in an emergency department, a same-day access clinic, or an infusion centre) or unscheduled visits to a healthcare provider for administration of an intravenous diuretic as accepted by FDA and an increase in chronic heart failure therapy

    4. Total number of Cardiovascular hospitalizations [Baseline to a minimum of 24 months]

      Cardiovascular hospitalizations

    5. Safety (Adverse Events) [Baseline to a minimum of 24 months]

      Thromboembolic events, symptomatic Pulmonary vein stenosis, atrio-esophageal fistula, pericardial effusion requiring pericardiocentesis, major bleeding requiring blood transfusion, amiodarone induced thyroid, pulmonary and other toxicity

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Patients with one of the following AF categories and at least one ECG documentation of AF
    • High burden Paroxysmal defined as ≥ 4 episodes of AF in the last 6 months, and at least one episode > 6 hours (and no episode requiring cardioversion and no episode > 7 days)

    • Persistent AF (1) defined as ≥ 4 episodes of AF in the last 6 months, and at least one episode > 6 hours, and at least one AF episode less than 7 days but requires cardioversion. No AF episodes are > 7 days

    • Persistent AF (2) as defined by at least one episode of AF > 7 days but not > 1 year

    • Long term persistent AF defined as an AF episode, at least one year in length and no episodes > 3 years

    1. Optimal therapy for heart failure of at least 6 weeks (according to 2009 ACCF/AHA class 1 recommendations).

    2. HF with NYHA class II or III symptoms with either impaired LV function (LVEF ≤ 45%) as determined by EF assessment within the previous 12 months or preserved LV function (LVEF > 45%) determined by by EF assessment within the previous 12 months

    3. NT-pro BNP measures:

    1. Patient has been hospitalized for Heart Failure* in the past 9 months, has been discharged AND:

    i- Is presently in Normal Sinus Rhythm and NT-pro BNP is ≥ 400 pg/mL

    ii- Is presently in Atrial Fibrillation and NT-pro BNP is ≥ 600 pg/mL

    OR

    B) Patient has had no hospitalization for Heart Failure in the past 9 months AND:

    i- Has had paroxysmal Atrial Fibrillation, is presently in Normal Sinus Rhythm and NT-proBNP is ≥ 600 pg/mL

    ii- Is presently in Atrial Fibrillation and NT-proBNP is ≥ 900 pg/mL

    *Heart Failure Admission is defined as admission to hospital > 24 hours and received treatment for Heart failure

    1. Suitable candidate for catheter ablation or rate control therapy for the treatment of AF

    2. Age ≥18

    Exclusion Criteria:
    1. Have an LA dimension > 55 mm as determined by an echocardiography within the previous year

    2. Had an acute coronary syndrome or coronary artery bypass surgery within 12 weeks

    3. Have rheumatic heart disease, severe aortic or mitral valvular heart disease using the AHA/ACC guidelines

    4. Have congenital heart disease including previous ASD repair, persistent left superior vena cava

    5. Had prior surgical or percutaneous AF ablation procedure or atrioventricular nodal (AVN) ablation

    6. Have a medical condition likely to limit survival to < 1 year

    7. Have New York Heart Association (NYHA) class IV heart failure symptoms

    8. Have contraindication to systematic anticoagulation

    9. Have renal failure requiring dialysis

    10. AF due to reversible cause e.g. hyperthyroid state

    11. Are pregnant

    12. Are included in other clinical trials that will affect the objectives of this study

    13. Have a history of non-compliance to medical therapy

    14. Are unable or unwilling to provide informed consent

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Instituto de Cardiologia-FUC RSPorto AlegreRio Grande Do SulBrazil90620-001
    2Libin Cardiovascular Institute of Alberta, CalgaryCalgaryAlbertaCanadaT2N 2T9
    3Royal Alexandra HospitalEdmontonAlbertaCanadaT5H 3V9
    4Vancouver GeneralVancouverBritish ColumbiaCanadaV6Z 1Y6
    5Royal Jubilee HospitalVictoriaBritish ColumbiaCanadaV8R 4R2
    6Queen Elizabeth II Health ScienceHalifaxNova ScotiaCanadaB3H 3A7
    7Hamilton Health Sciences CentreHamiltonOntarioCanadaL8L 2X2
    8Kingston General HospitalKingstonOntarioCanadaK7L 2V7
    9St. Mary's General HospitalKitchenerOntarioCanadaN2M 1B2
    10London Health Sciences CentreLondonOntarioCanadaN6A 5A5
    11Southlake Regional Health CareNewmarketOntarioCanadaL3Y 8C3
    12University of Ottawa Heart InstituteOttawaOntarioCanadaK1Y 4W7
    13Sunnybrook Health Sciences CentreTorontoOntarioCanadaM4N 3M5
    14Toronto General Hospital, University Health NetworkTorontoOntarioCanadaM5G 2M9
    15Institute de Cardiologie de MontréalMontrealQuebecCanadaH1T 1C8
    16CHUM Centre hospitalier universitaire de MontréalMontrealQuebecCanadaH2L 4M1
    17McGill University Health CentreMontrealQuebecCanadaH3A 1A1
    18Insitut universitaire de cardiologie and pneumologie de QuebecQuebec CityQuebecCanadaG1V 4G5
    19CHUS Centre Hospitalier Universitaire de SherbrookeSherbrookeQuebecCanadaJ1H 5N4
    20Karolinska University HospitalStockholmSwedenS-171 76
    21National Taiwan University HospitalTaipeiTaiwan100

    Sponsors and Collaborators

    • Ottawa Heart Institute Research Corporation
    • Canadian Institutes of Health Research (CIHR)

    Investigators

    • Principal Investigator: Anthony Tang, MD FRCPC, Western University
    • Principal Investigator: George Wells, PhD, Ottawa Heart Institute Research Corporation

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Ottawa Heart Institute Research Corporation
    ClinicalTrials.gov Identifier:
    NCT01420393
    Other Study ID Numbers:
    • 231888
    First Posted:
    Aug 19, 2011
    Last Update Posted:
    Oct 8, 2021
    Last Verified:
    Sep 1, 2021
    Keywords provided by Ottawa Heart Institute Research Corporation
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 8, 2021