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

Locations

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 Disease	Intervention/Treatment	Phase
Heart Failure Atrial Fibrillation	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

Arm	Intervention/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

Arm

Intervention/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

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

All-cause mortality [Baseline to a minimum of 24 months]
All-cause mortality
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
Health related QoL [Baseline to a minimum of 24 months]
Minnesota Living with Heart Failure. Scoring: The higher the score, the worse the HRQL
Health related QoL [Baseline to a minimum of 24 months]
EuroQol- 5 Dimension. Scoring 0 = worst to 100 = best
Health related QoL [Baseline to a minimum of 24 months]
Atrial Fibrillation Effect on Quality-of-life. Scoring 0 = worst to 100 = best
Exercise capacity [Baseline to a minimum of 24 months]
as determined by 6 Minute Hall walk distance
NT-proBNP/BNP at 1 year and at 2 year follow-up [Baseline to a minimum of 24 months]
NT-proBNP/BNP
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]
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]
Health economics [Baseline to a minimum of 24 months]
Cost economics

Other Outcome Measures

LV function and remodeling (LVESVi) at 1 year and 2 year follow-up [Baseline to a minimum of 24 months]
Echocardiogram measure LVESVi
AF Burden at 1 year and 2 year follow-up [Baseline to a minimum of 24 months]
14 Day Continuous ECG monitoring
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
Total number of Cardiovascular hospitalizations [Baseline to a minimum of 24 months]
Cardiovascular hospitalizations
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:

Inclusion Criteria:

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

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

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

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

Suitable candidate for catheter ablation or rate control therapy for the treatment of AF
Age ≥18

Exclusion Criteria:

Have an LA dimension > 55 mm as determined by an echocardiography within the previous year
Had an acute coronary syndrome or coronary artery bypass surgery within 12 weeks
Have rheumatic heart disease, severe aortic or mitral valvular heart disease using the AHA/ACC guidelines
Have congenital heart disease including previous ASD repair, persistent left superior vena cava
Had prior surgical or percutaneous AF ablation procedure or atrioventricular nodal (AVN) ablation
Have a medical condition likely to limit survival to < 1 year
Have New York Heart Association (NYHA) class IV heart failure symptoms
Have contraindication to systematic anticoagulation
Have renal failure requiring dialysis
AF due to reversible cause e.g. hyperthyroid state
Are pregnant
Are included in other clinical trials that will affect the objectives of this study
Have a history of non-compliance to medical therapy
Are unable or unwilling to provide informed consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Instituto de Cardiologia-FUC RS	Porto Alegre	Rio Grande Do Sul	Brazil	90620-001
2	Libin Cardiovascular Institute of Alberta, Calgary	Calgary	Alberta	Canada	T2N 2T9
3	Royal Alexandra Hospital	Edmonton	Alberta	Canada	T5H 3V9
4	Vancouver General	Vancouver	British Columbia	Canada	V6Z 1Y6
5	Royal Jubilee Hospital	Victoria	British Columbia	Canada	V8R 4R2
6	Queen Elizabeth II Health Science	Halifax	Nova Scotia	Canada	B3H 3A7
7	Hamilton Health Sciences Centre	Hamilton	Ontario	Canada	L8L 2X2
8	Kingston General Hospital	Kingston	Ontario	Canada	K7L 2V7
9	St. Mary's General Hospital	Kitchener	Ontario	Canada	N2M 1B2
10	London Health Sciences Centre	London	Ontario	Canada	N6A 5A5
11	Southlake Regional Health Care	Newmarket	Ontario	Canada	L3Y 8C3
12	University of Ottawa Heart Institute	Ottawa	Ontario	Canada	K1Y 4W7
13	Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4N 3M5
14	Toronto General Hospital, University Health Network	Toronto	Ontario	Canada	M5G 2M9
15	Institute de Cardiologie de Montréal	Montreal	Quebec	Canada	H1T 1C8
16	CHUM Centre hospitalier universitaire de Montréal	Montreal	Quebec	Canada	H2L 4M1
17	McGill University Health Centre	Montreal	Quebec	Canada	H3A 1A1
18	Insitut universitaire de cardiologie and pneumologie de Quebec	Quebec City	Quebec	Canada	G1V 4G5
19	CHUS Centre Hospitalier Universitaire de Sherbrooke	Sherbrooke	Quebec	Canada	J1H 5N4
20	Karolinska University Hospital	Stockholm		Sweden	S-171 76
21	National Taiwan University Hospital	Taipei		Taiwan	100

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