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

Heart Failure Clinical Trial

— RAFT-AF  

Official title:

A Randomized Ablation-based Atrial Fibrillation Rhythm Control Versus Rate Control Trial in Patients With Heart Failure and High Burden Atrial Fibrillation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01420393
• Other study ID #: 231888
• Status: Completed
• Phase: N/A
• Start date: September 2011
• Est. completion date: June 2021

Study information

• Verified date: October 2021
• Source: Ottawa Heart Institute Research Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 411
• Est. completion date: June 2021
• Est. primary completion date: May 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation
• Heart Failure

Intervention

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:
• 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.

Locations

Country	Name	City	State
Brazil	Instituto de Cardiologia-FUC RS	Porto Alegre	Rio Grande Do Sul
Canada	Libin Cardiovascular Institute of Alberta, Calgary	Calgary	Alberta
Canada	Royal Alexandra Hospital	Edmonton	Alberta
Canada	Queen Elizabeth II Health Science	Halifax	Nova Scotia
Canada	Hamilton Health Sciences Centre	Hamilton	Ontario
Canada	Kingston General Hospital	Kingston	Ontario
Canada	St. Mary's General Hospital	Kitchener	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	CHUM Centre hospitalier universitaire de Montréal	Montreal	Quebec
Canada	Institute de Cardiologie de Montréal	Montreal	Quebec
Canada	McGill University Health Centre	Montreal	Quebec
Canada	Southlake Regional Health Care	Newmarket	Ontario
Canada	University of Ottawa Heart Institute	Ottawa	Ontario
Canada	Insitut universitaire de cardiologie and pneumologie de Quebec	Quebec City	Quebec
Canada	CHUS Centre Hospitalier Universitaire de Sherbrooke	Sherbrooke	Quebec
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	Toronto General Hospital, University Health Network	Toronto	Ontario
Canada	Vancouver General	Vancouver	British Columbia
Canada	Royal Jubilee Hospital	Victoria	British Columbia
Sweden	Karolinska University Hospital	Stockholm
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (2)

Lead Sponsor	Collaborator
Ottawa Heart Institute Research Corporation	Canadian Institutes of Health Research (CIHR)

Countries where clinical trial is conducted

Brazil,  Canada,  Sweden,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	LV function and remodeling (LVESVi) at 1 year and 2 year follow-up	Echocardiogram measure LVESVi	Baseline to a minimum of 24 months
Other	AF Burden at 1 year and 2 year follow-up	14 Day Continuous ECG monitoring	Baseline to a minimum of 24 months
Other	Total number of heart failure events	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	Baseline to a minimum of 24 months
Other	Total number of Cardiovascular hospitalizations	Cardiovascular hospitalizations	Baseline to a minimum of 24 months
Other	Safety (Adverse Events)	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	Baseline to a minimum of 24 months
Primary	Composite of all-cause mortality and heart failure events	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	Baseline to a minimum of 24 months
Secondary	All-cause mortality	All-cause mortality	Baseline to a minimum of 24 months
Secondary	Heart Failure events	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	Baseline to a minimum of 24 months
Secondary	Health related QoL	Minnesota Living with Heart Failure. Scoring: The higher the score, the worse the HRQL	Baseline to a minimum of 24 months
Secondary	Health related QoL	EuroQol- 5 Dimension. Scoring 0 = worst to 100 = best	Baseline to a minimum of 24 months
Secondary	Health related QoL	Atrial Fibrillation Effect on Quality-of-life. Scoring 0 = worst to 100 = best	Baseline to a minimum of 24 months
Secondary	Exercise capacity	as determined by 6 Minute Hall walk distance	Baseline to a minimum of 24 months
Secondary	NT-proBNP/BNP at 1 year and at 2 year follow-up	NT-proBNP/BNP	Baseline to a minimum of 24 months
Secondary	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
Secondary	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
Secondary	Health economics	Cost economics	Baseline to a minimum of 24 months