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| Name | Class |
|---|---|
| Canadian Institutes of Health Research (CIHR) | OTHER_GOV |
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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.
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.
Updated June 2024:
Additional analysis will be completed using the winratio analysis for the hierarchical primary outcome of:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 study completion, an average of 24 months |
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Inclusion Criteria:
Patients with one of the following AF categories and at least one ECG documentation of AF
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
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
Suitable candidate for catheter ablation or rate control therapy for the treatment of AF
Age ≥18
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Anthony Tang, MD FRCPC | Western University | Principal Investigator |
| George Wells, PhD | Ottawa Heart Institute Research Corporation | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Instituto de Cardiologia-FUC RS | Porto Alegre | Rio Grande do Sul | 90620-001 | Brazil | ||
| Libin Cardiovascular Institute of Alberta, Calgary |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35313733 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. 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 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 18, 2020 |
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| 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. |
|
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| Calgary |
| Alberta |
| T2N 2T9 |
| Canada |
| Royal Alexandra Hospital | Edmonton | Alberta | T5H 3V9 | Canada |
| Vancouver General | Vancouver | British Columbia | V6Z 1Y6 | Canada |
| Royal Jubilee Hospital | Victoria | British Columbia | V8R 4R2 | Canada |
| Queen Elizabeth II Health Science | Halifax | Nova Scotia | B3H 3A7 | Canada |
| Hamilton Health Sciences Centre | Hamilton | Ontario | L8L 2X2 | Canada |
| Kingston General Hospital | Kingston | Ontario | K7L 2V7 | Canada |
| St. Mary's General Hospital | Kitchener | Ontario | N2M 1B2 | Canada |
| London Health Sciences Centre | London | Ontario | N6A 5A5 | Canada |
| Southlake Regional Health Care | Newmarket | Ontario | L3Y 8C3 | Canada |
| University of Ottawa Heart Institute | Ottawa | Ontario | K1Y 4W7 | Canada |
| Sunnybrook Health Sciences Centre | Toronto | Ontario | M4N 3M5 | Canada |
| Toronto General Hospital, University Health Network | Toronto | Ontario | M5G 2M9 | Canada |
| Institute de Cardiologie de Montréal | Montreal | Quebec | H1T 1C8 | Canada |
| CHUM Centre hospitalier universitaire de Montréal | Montreal | Quebec | H2L 4M1 | Canada |
| McGill University Health Centre | Montreal | Quebec | H3A 1A1 | Canada |
| Insitut universitaire de cardiologie and pneumologie de Quebec | Québec | Quebec | G1V 4G5 | Canada |
| CHUS Centre Hospitalier Universitaire de Sherbrooke | Sherbrooke | Quebec | J1H 5N4 | Canada |
| Karolinska University Hospital | Stockholm | S-171 76 | Sweden |
| National Taiwan University Hospital | Taipei | 100 | Taiwan |
| FG001 | 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. 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. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. 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 |
| BG001 | 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. 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. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||||
| 6 Minute walk distance | Mean | Standard Deviation | metres |
| |||||||||||||||||
| NT-proBNP | Median | Full Range | pg/mL |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | Posted | Count of Participants | Participants | Baseline to study completion, an average of 24 months |
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|
Baseline to study completion
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 29 | 214 | 88 | 214 | 66 | 214 |
| EG001 | 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. | 34 | 197 | 73 | 197 | 68 | 197 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| CV hospitalizaton | Cardiac disorders | Systematic Assessment |
| ||
| Ablation related hospitalizations | Cardiac disorders | Systematic Assessment |
| ||
| Device implant related | Cardiac disorders | Systematic Assessment |
| ||
| AV node ablation hospitalizations | Cardiac disorders | Systematic Assessment |
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| Total Hospitalizations | General disorders | Systematic Assessment | The total number of hospitalizations is greater than the number of participants, as some participants had more than 1 hospitalization throughout the study reporting period. |
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| Atrioesophageal fistula | Cardiac disorders | Systematic Assessment |
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| Pericardial Effusion | Cardiac disorders | Systematic Assessment | Required pericardiocentesis |
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| Major bleed | General disorders | Systematic Assessment |
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| Minor bleed | General disorders | Systematic Assessment |
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| Bradycardia | Cardiac disorders | Systematic Assessment |
| ||
| Amiodarone-induced toxicity | General disorders | Systematic Assessment |
| ||
| Stroke | General disorders | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| NON CV hospitalizations | General disorders | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Anthony Tang | Western University | 519-663-3764 | anthonysltang@gmail.com |
| Aug 24, 2022 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D006333 | Heart Failure |
| D001281 | Atrial Fibrillation |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D001145 | Arrhythmias, Cardiac |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D017115 | Catheter Ablation |
| D006339 | Heart Rate |
| ID | Term |
|---|---|
| D000078703 | Radiofrequency Ablation |
| D000078702 | Radiofrequency Therapy |
| D013812 | Therapeutics |
| D055011 | Ablation Techniques |
| D013514 | Surgical Procedures, Operative |
| D055986 | Vital Signs |
| D010808 | Physical Examination |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D006439 | Hemodynamics |
| D002320 | Cardiovascular Physiological Phenomena |
| D002943 | Circulatory and Respiratory Physiological Phenomena |
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| >=65 years |
|
| Male |
|
| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
|
| Unknown or Not Reported |
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| Sweden |
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| Taiwan |
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| Brazil |
|