Clinical trial NCT01420393: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Heart Failure
Atrial Fibrillation
Keywords: Heart Failure
Atrial Fibrillation
Catheter Ablation
Anti-arrhythmic Medications
Cardiovascular Mortality
Lead sponsor: Ottawa Heart Institute Research Corporation
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2011-08-19
Enrollment: 411
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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
2. Optimal therapy for heart failure of at least 6 weeks (according to 2009 ACCF/AHA class 1 recommendations).
3. 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
4. NT-pro BNP measures:

   A) 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
5. Suitable candidate for catheter ablation or rate control therapy for the treatment of AF
6. 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

Primary outcomes:
measure: Composite of all-cause mortality and heart failure events
timeFrame: Baseline to a minimum of 24 months
Secondary outcomes:
measure: All-cause mortality
timeFrame: Baseline to a minimum of 24 months
measure: Heart Failure events
timeFrame: Baseline to a minimum of 24 months
measure: Health related QoL
timeFrame: Baseline to a minimum of 24 months
measure: Health related QoL
timeFrame: Baseline to a minimum of 24 months
measure: Health related QoL
timeFrame: Baseline to a minimum of 24 months
measure: Exercise capacity
timeFrame: Baseline to a minimum of 24 months
measure: NT-proBNP/BNP at 1 year and at 2 year follow-up
timeFrame: Baseline to a minimum of 24 months
measure: All-cause mortality and heart failure events in patients with HF, impaired (LVEF≤45%) LV function and high burden AF
timeFrame: Baseline to a minimum of 24 months
measure: All-cause mortality and heart failure events in patients with HF, preserved (LVEF > 45%) LV function and high burden AF
timeFrame: Baseline to a minimum of 24 months
measure: Health economics
timeFrame: Baseline to a minimum of 24 months
Other outcomes:
measure: LV function and remodeling (LVESVi) at 1 year and 2 year follow-up
timeFrame: Baseline to a minimum of 24 months
measure: AF Burden at 1 year and 2 year follow-up
timeFrame: Baseline to a minimum of 24 months
measure: Total number of heart failure events
timeFrame: Baseline to a minimum of 24 months
measure: Total number of Cardiovascular hospitalizations
timeFrame: Baseline to a minimum of 24 months
measure: Safety (Adverse Events)
timeFrame: Baseline to a minimum of 24 months
Locations:
city: Porto Alegre
country: Brazil
facility: Instituto de Cardiologia-FUC RS
state: Rio Grande Do Sul
city: Calgary
country: Canada
facility: Libin Cardiovascular Institute of Alberta, Calgary
state: Alberta
city: Edmonton
country: Canada
facility: Royal Alexandra Hospital
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General
state: British Columbia
city: Victoria
country: Canada
facility: Royal Jubilee Hospital
state: British Columbia
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Science
state: Nova Scotia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences Centre
state: Ontario
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: Kitchener
country: Canada
facility: St. Mary's General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Newmarket
country: Canada
facility: Southlake Regional Health Care
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital, University Health Network
state: Ontario
city: Montreal
country: Canada
facility: Institute de Cardiologie de Montréal
state: Quebec
city: Montreal
country: Canada
facility: CHUM Centre hospitalier universitaire de Montréal
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Quebec City
country: Canada
facility: Insitut universitaire de cardiologie and pneumologie de Quebec
state: Quebec
city: Sherbrooke
country: Canada
facility: CHUS Centre Hospitalier Universitaire de Sherbrooke
state: Quebec
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: Western University
name: Anthony Tang, MD FRCPC
role: PRINCIPAL_INVESTIGATOR
affiliation: Ottawa Heart Institute Research Corporation
name: George Wells, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Parkash R, Wells GA, Rouleau J, Talajic M, Essebag V, Skanes A, Wilton SB, Verma A, Healey JS, Sterns L, Bennett M, Roux JF, Rivard L, Leong-Sit P, Jensen-Urstad M, Jolly U, Philippon F, Sapp JL, Tang ASL. Randomized Ablation-Based Rhythm-Control Versus Rate-Control Trial in Patients With Heart Failure and Atrial Fibrillation: Results from the RAFT-AF trial. Circulation. 2022 Jun 7;145(23):1693-1704. doi: 10.1161/CIRCULATIONAHA.121.057095. Epub 2022 Mar 22.