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

NCT01420393 | Completed DMC

• 1 other identifier: 231888
• Study Type: interventional
• Target: 411
• Locations: 4 countries
• Sites: 21

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.

Conditions

Heart Failure; Atrial Fibrillation

Keywords

Heart Failure; Atrial Fibrillation; Catheter Ablation; Anti-arrhythmic Medications; Cardiovascular Mortality

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• All-cause mortality

  Baseline to a minimum of 24 months

• Heart Failure events

  Baseline to a minimum of 24 months

• Health related QoL

  Baseline to a minimum of 24 months

• Health related QoL

  Baseline to a minimum of 24 months

• Health related QoL

  Baseline to a minimum of 24 months

Other Outcomes (5)

• LV function and remodeling (LVESVi) at 1 year and 2 year follow-up

  Baseline to a minimum of 24 months

• AF Burden at 1 year and 2 year follow-up

  Baseline to a minimum of 24 months

• Total number of heart failure events

  Baseline to a minimum of 24 months

Study Arms (2)

Rhythm Control

ACTIVE COMPARATOR

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

Rate Control

ACTIVE COMPARATOR

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

Interventions

Rhythm control PROCEDURE

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

Also known as: Catheter ablation

Rhythm Control

Rate Control OTHER

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.

Also known as: Standard medical therapy

Rate Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (21)

Instituto de Cardiologia-FUC RS

Porto Alegre, Rio Grande do Sul, 90620-001, Brazil

Location

Libin Cardiovascular Institute of Alberta, Calgary

Calgary, Alberta, T2N 2T9, Canada

Location

Royal Alexandra Hospital

Edmonton, Alberta, T5H 3V9, Canada

Location

Vancouver General

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

Royal Jubilee Hospital

Victoria, British Columbia, V8R 4R2, Canada

Location

Queen Elizabeth II Health Science

Halifax, Nova Scotia, B3H 3A7, Canada

Location

Hamilton Health Sciences Centre

Hamilton, Ontario, L8L 2X2, Canada

Location

Kingston General Hospital

Kingston, Ontario, K7L 2V7, Canada

Location

St. Mary's General Hospital

Kitchener, Ontario, N2M 1B2, Canada

Location

London Health Sciences Centre

London, Ontario, N6A 5A5, Canada

Location

Southlake Regional Health Care

Newmarket, Ontario, L3Y 8C3, Canada

Location

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y 4W7, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Toronto General Hospital, University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

Institute de Cardiologie de Montréal

Montreal, Quebec, H1T 1C8, Canada

Location

CHUM Centre hospitalier universitaire de Montréal

Montreal, Quebec, H2L 4M1, Canada

Location

McGill University Health Centre

Montreal, Quebec, H3A 1A1, Canada

Location

Insitut universitaire de cardiologie and pneumologie de Quebec

Québec, Quebec, G1V 4G5, Canada

Location

CHUS Centre Hospitalier Universitaire de Sherbrooke

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Karolinska University Hospital

Stockholm, S-171 76, Sweden

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Related Publications (1)

• 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.

  PMID: 35313733 DERIVED

MeSH Terms

Conditions

Heart Failure; Atrial Fibrillation

Interventions

Catheter Ablation; Heart Rate

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Radiofrequency Ablation; Radiofrequency Therapy; Therapeutics; Ablation Techniques; Surgical Procedures, Operative; Vital Signs; Physical Examination; Diagnostic Techniques and Procedures; Diagnosis; Hemodynamics; Cardiovascular Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Study Officials

• Anthony Tang, MD FRCPC

  Western University

  PRINCIPAL INVESTIGATOR

• George Wells, PhD

  Ottawa Heart Institute Research Corporation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2011
• First Posted: August 19, 2011
• Study Start: September 1, 2011
• Primary Completion: May 1, 2021
• Study Completion: June 1, 2021
• Last Updated: October 21, 2021

Record last verified: 2021-10

Locations

BR (1); SE (1); CA (18); TW (1)