CABANA: Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial
Sponsor
Mayo Clinic (Other)
Overall Status
Completed
CT.gov ID
NCT00911508
Collaborator
National Heart, Lung, and Blood Institute (NHLBI) (NIH), Abbott Medical Devices (Industry), Biosense Webster, Inc. (Industry)
2,204
118
2
97.6
18.7
0.2
Study Details
Study Description
Brief Summary
The (Catheter Ablation Versus Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial) CABANA Trial has the overall goal of establishing the appropriate roles for medical and ablative intervention for atrial fibrillation (AF). The CABANA Trial is designed to test the hypothesis that the treatment strategy of left atrial catheter ablation for the purpose of eliminating atrial fibrillation (AF) will be superior to current state-of-the-art therapy with either rate control or rhythm control drugs for decreasing the incidence of the composite endpoint of total mortality, disabling stroke, serious bleeding, or cardiac arrest in patients with untreated or incompletely treated AF.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
The need for this trial arises out of 1) the rapidly increasing number of pts > 60 years of age with AF accompanied by symptoms and morbidity, 2) the failure of anti-arrhythmic drug therapy to maintain sinus rhythm and reduce mortality, 3) the rapidly increasing application of radio-frequency catheter ablation without appropriate evidence-based validation, and 4) the expanding impact of AF on health care costs.
This study will randomize up to 2200 patients to a strategy of catheter ablation versus pharmacologic therapy with rate or rhythm control drugs. Each pt will have 1) characteristics similar to AFFIRM pts (≥65 yo or <65 with >1 risk factor for stroke, 2) Documented AF warranting treatment, and 3) Eligibility for both catheter ablation and ≥2 anti-arrhythmic or ≥2 rate control drugs. Pts will be followed every 6 months for an average of approximately 5 years and will undergo repeat trans-telephonic monitor, Holter monitor, and CT/MR studies to assess the impact of treatment.
The CABANA trial will disclose the role of medical and non-pharmacologic therapies for AF, establish the cost and impact of therapy on quality of life and will help determine if AF is a modifiable risk factor for increased mortality.
Study Design
Study Type:
Interventional
Actual Enrollment
:
2204 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial
Actual Study Start Date
:
Nov 13, 2009
Actual Primary Completion Date
:
Dec 31, 2017
Actual Study Completion Date
:
Dec 31, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Left Atrial Ablation Pulmonary vein isolation using a circumferential ablative approach in the left atrium. Ablation may be performed using circular mapping catheter-guided ablation, antral isolation using a circular guided approach, or wide area circumferential ablation. |
Device: Left atrial ablation
St. Jude: Livewire TC™ , Therapy™ Dual / Thermocouple, Safire,Therapy Cool Path
Biosense Webster: NAVI-STAR, NAVI-STAR/NAVI-STAR DS, Celsius Braided/Long Tip, NAVI-STAR™ and Celsius™ ThermoCool, NAVI-STAR® RMT, Celsius® RMT, ThermoCool® SF
Medtronic CryoCath LP: Freezor®/Freezor MAX®, Artic Front®, Cardiac Ablation System
Bard: Stinger
Boston Scientific: Blazer II RF/XP, Blazer RPM, Chilli II Cooled, SteeroCath
|
| Active Comparator: Rate or Rhythm Control Therapy Current state-of-the-art drug therapy for atrial fibrillation (rate control or rhythm control). Treating physicians will be encouraged to follow the American College of Cardiology / American Heart Association / European Society of Cardiology Atrial Fibrillation Guidelines with regard to drug therapy for atrial fibrillation. The specific choice of rate control versus rhythm control drug therapy and the specific drugs to be used will ultimately be left to the discretion of the treating physician. |
Drug: Rate or Rhythm Control Therapy
Rate control: Metoprolol 50-100mg, Atenolol 50-100mg, Propranolol 40-80mg, Acebutolol 200-300mg, Carvedilol 6.25-25mg, Diltiazem 180-240mg, Verapamil 180-240mg, Digoxin 0.125-0.25mg
Rhythm control: Propafenone 450-625mg, Flecainide 200-300mg, Sotalol 240-320mg, Dofetilide 500-1000mcg, Amiodarone 200-400mg, Quinidine 600-900mg, Dronedarone 800mg
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Composite of Total Mortality, Disabling Stroke, Serious Bleeding, or Cardiac Arrest in Patients Warranting Therapy for AF. [From date of enrollment until time-to-first event over a median follow-up of 48.5 months.]
All events for each component of the primary endpoint were reviewed and adjudicated in a blinded fashion by an independent clinical events committee using prospectively determined event definitions. Death was defined as all-cause mortality, disabling stroke (including intracranial bleeding) as an irreversible physical limitation defined by a Rankin Stroke Scale ≥2, and serious bleeding as bleeding accompanied by hemodynamic compromise that required surgical intervention or a transfusion of ≥3 units of blood.
Secondary Outcome Measures
- Number of Participants With All-cause Mortality [From date of enrollment until date of death over a median follow-up of 48.5 months.]
All deaths were reviewed and adjudicated by the Clinical Events Committee
- Number of Participants With Mortality or Cardiovascular (CV) Hospitalization [From date of enrollment until time-to-first event of death or CV hospitalization over a median follow-up of 48.5 months.]
Hospitalization was characterized by the site principal investigator (PI) and reported as part of the hospitalization case report form.
- Number of Participants With Mortality, Disabling Stroke, or CV Hospitalization (for Heart Failure or Acute Ischemic Events) [From date of enrollment until time-to-first event of death, stroke, or CV hospitalization (for heart failure or acute ischemic event) over a median follow-up of 48.5 months.]
Disabling stroke (including intracranial bleeding) was defined as an irreversible physical limitation defined by a Rankin Stroke Scale ≥2 and the reason for hospitalization was characterized by the site PI and reported as part of the hospitalization case report form.
- Number of Participants With Cardiovascular Death [From date of enrollment until date of a cardiovascular death over a median follow-up of 48.5 months.]
Cardiovascular death as determined by the Clinical Events Committee based on the available data provided by the Principal Investigator
- Number of Participants With Cardiovascular Death or Disabling Stroke [From date of enrollment until time-to-first event of a cardiovascular death or disabling stroke over a median follow-up of 48.5 months.]
Disabling stroke (including intracranial bleeding) was defined as an irreversible physical limitation defined by a Rankin Stroke Scale ≥2.
- Number of Participants With an Arrhythmic Death or Cardiac Arrest [From date of enrollment until time-to-first event for an arrhythmic death or cardiac arrest over a median follow-up of 48.5 months.]
All deaths and cardiac arrest events were adjudicated by the Clinical Events Committee
- Number of Participants With Heart Failure Death [From date of enrollment until date of heart failure death over a median follow-up of 48.5 months.]
All deaths were categorized and adjudicated by the Clinical Events Committee
- Number of Participants Free From Recurrent Atrial Fibrillation (AF) Following the 90 Day Blanking Period [From date of therapy initiation until date of first AF recurrence following a 90 day wait (blanking) period over a median follow-up of 48.5 months.]
Data from patients using the study provided ECG event recording system were analyzed. A 30-second episode of AF in either group, confirmed through blinded review by an ECG Core Lab Committee was used for defining the endpoint of recurrent AF.
- Number of Participants With Cardiovascular Hospitalization [From date of enrollment until date of cardiovascular hospitalization over a median follow-up of 48.5 months.]
The reason for hospitalization was characterized by the site PI and reported as part of the hospitalization case report form.
- Changes in Quality of Life Measures - AFEQT [Baseline ,12 month, 5 years]
Atrial Fibrillation Effect on Quality of Life (AFEQT) Overall Score (Scale: 0 = complete disability, 100 = no disability). The AFEQT is a 21-item AF-specific, health-related QOL questionnaire designed to assess the effect of atrial fibrillation on patient quality of life. The AFEQT has an Overall Score (calculated from 18 of the questions) and subscale scores in three domains: symptoms, daily activities, and treatment concern. Overall and subscale scores range from 0 (corresponds to complete disability) to 100 (no AF-related disability).
- Changes in Quality of Life Measures - MAFSI Frequency Score [Baseline, 12 Month, 5 Year]
The Mayo AF-Specific Symptom Inventory (MAFSI) is a questionnaire comprised of a 10-item AF symptom checklist that asked about both the frequency and severity of each symptom. MAFSI frequency of symptoms over the past month was recorded as 0 (never), 1 (rarely), 2 (sometimes), 3 (often), and 4 (always) for each of the 10 items listed in the questionnaire. The 10 item responses were summed for a total Frequency Score that ranged from 0 (no AF symptoms) to 40 (worst score).
- Changes in Quality of Life Measures - MAFSI Severity Score [Baseline, 12 Month, 5 Year]
The Mayo AF-Specific Symptom Inventory (MAFSI) is a questionnaire comprised of a 10-item AF symptom checklist that asked about both the frequency and severity of each symptom. MAFSI severity scores over the past month were recorded as 1 (mild), 2 (moderate), and 3 (extreme) for each of the 10 items listed in the questionnaire. The 10 items items were then summed for the total Severity Score that ranged from 0 (no AF symptoms) to 30 (most severe AF symptoms).
- Number of Participants With Adverse Events/Complications [From treatment start date to date of event over a median follow-up of 48.5 months.]
Comparing individual non-endpoint adverse events between ablative and drug therapy is difficult due to the substantial difference in the types of adverse events expected. Ablation-related events were counted among all patients that were randomized to and received an ablation. Drug-related events were counted among all patients that were randomized to and received drug therapy.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 90 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
- Over the preceding 6 months have:
-
≥2 paroxysmal (electrocardiographic documentation of at least 1) atrial fibrillation (AF) episodes lasting ≥1 hour in duration: (that terminate spontaneously within 7 days or cardioversion is performed within 48h of AF onset): or
-
electrocardiographic documentation of 1 persistent AF episode: (sustained for ≥7 days or cardioversion is performed more than 48h after AF onset): or
-
electrocardiographic documentation of 1 longstanding persistent AF episode: (continuous AF of duration >1 year).
-
Warrant active therapy (within the past 3 months) beyond simple ongoing observation
-
Be eligible for catheter ablation and ≥2 sequential rhythm control and/or ≥2 rate control drugs.
-
Be ≥65 yrs of age, or <65 yrs with one or more of the following risk factors for stroke: Hypertension (treated and/or defined as a blood pressure >140/90 mmHg) [90], Diabetes (treated and/or defined as a fasting glucose ≥126 mg/dl) [91], Congestive heart failure (including systolic or diastolic heart failure), Prior stroke, transient ischemic attack or systemic emboli, Atherosclerotic vascular disease (previous myocardial infarction (MI), peripheral arterial disease or aortic plaque), left atrial (LA) size >5.0 cm (or volume index ≥40 cc/m2), or ejection fraction (EF) ≤35.
-
Have the capacity to understand and sign an informed consent form.
-
Be ≥18 years of age.
-
NOTE- Subjects <65 yrs of age whose only risk factor is hypertension must have a second risk factor or left ventricular (LV) hypertrophy to qualify.Patients receiving new drug therapy initiated within the previous 3 months may continue that therapy if randomized to the drug therapy arm. Patients may have documented atrial flutter in addition to atrial fibrillation and remain eligible for enrollment.
Exclusion Criteria:
-
Lone AF in the absence of risk factors for stroke in patients <65 years of age
-
Patients who in the opinion of the managing clinician should not yet receive any therapy for AF
-
Patients who have failed >2 membrane active anti-arrhythmic drugs at a therapeutic dose due to inefficacy or side effects (Table 5.2.2)
-
An efficacy failure of full dose amiodarone treatment >8 weeks duration at any time
-
Reversible causes of AF including thyroid disorders, acute alcohol intoxication, recent major surgical procedures, or trauma
-
Recent cardiac events including MI, percutaneous intervention (PCI), or valve or bypass surgery in the preceding 3 months
-
Hypertrophic obstructive cardiomyopathy (outflow track)
-
Class IV angina or Class IV congestive heart failure (CHF) (including past or planned heart transplantation)
-
Other arrhythmias mandating anti-arrhythmic drug therapy (i.e. ventricular tachycardia (VT), ventricular fibrillation (VF))
-
Heritable arrhythmias or increased risk for torsade de pointes with class I or III drugs
-
Prior LA catheter ablation with the intention of treating AF
-
Prior surgical interventions for AF such as the MAZE procedure
-
Prior AV nodal ablation
-
Patients with other arrhythmias requiring ablative therapy
-
Contraindication to appropriate anti-coagulation therapy
-
Renal failure requiring dialysis
-
Medical conditions limiting expected survival to <1 year
-
Women of childbearing potential (unless post-menopausal or surgically sterile)
-
Participation in any other clinical mortality trial (Participation in other non-mortality trials should be reviewed with the clinical trial management center)
-
Unable to give informed consent
-
NOTE- Prior ablation of the cavo-tricuspid isthmus alone is not an exclusion if the patient develops subsequent recurrent AF. Planned atrial flutter ablation in combination with the left atrial ablation is not an exclusion.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Arkansas Cardiology, PA | Little Rock | Arkansas | United States | 72205 |
| 2 | Good Samaritan Hospital | Los Angeles | California | United States | 90017 |
| 3 | University of California Los Angeles | Los Angeles | California | United States | 90095 |
| 4 | University of California Davis Medical Center | Sacramento | California | United States | 95817 |
| 5 | University of California at San Francisco Medical Center | San Francisco | California | United States | 94143 |
| 6 | Stanford University Medical Center | Stanford | California | United States | 94305 |
| 7 | The Medical Center of Aurora | Aurora | Colorado | United States | 80012 |
| 8 | Penrose Saint Francis Health Services | Colorado Springs | Colorado | United States | 80907 |
| 9 | Hartford Hospital | Hartford | Connecticut | United States | 06115 |
| 10 | George Washington University Medical Faculty Associates | Washington | District of Columbia | United States | 20037 |
| 11 | University of Miami Hospital | Miami | Florida | United States | 60612 |
| 12 | Florida Hospital | Orlando | Florida | United States | 32803 |
| 13 | Northside Hospital and Heart Institute | Saint Petersburg | Florida | United States | 33709 |
| 14 | Tallahassee Memorial Hospital | Tallahassee | Florida | United States | 32308 |
| 15 | Florida Heart Rhythm-University of South Florida College of Medicine | Tampa | Florida | United States | 33606 |
| 16 | Georgia Regents University | Augusta | Georgia | United States | 30912 |
| 17 | Georgia Arrhythmia Consultants & Research Institute | Macon | Georgia | United States | 31201 |
| 18 | Alexian Brothers Medical Center | Barrington | Illinois | United States | 60010 |
| 19 | Rush University Medical Center | Chicago | Illinois | United States | 60612 |
| 20 | NorthShore University Health System | Evanston | Illinois | United States | 60201 |
| 21 | Loyola University Medical Center | Maywood | Illinois | United States | 60153 |
| 22 | Mercy Medical Center-Iowa Heart Center | West Des Moines | Iowa | United States | 50226 |
| 23 | Johns Hopkins Hospital | Baltimore | Maryland | United States | 21287 |
| 24 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
| 25 | Brigham and Womens Hospital | Boston | Massachusetts | United States | 02115 |
| 26 | Henry Ford Hospital | Detroit | Michigan | United States | 48202 |
| 27 | Saint Joseph Mercy Hospital | Ypsilanti | Michigan | United States | 48197 |
| 28 | Minneapolis V.A. Medical Center | Minneapolis | Minnesota | United States | 55417 |
| 29 | Mayo Clinic Rochester | Rochester | Minnesota | United States | 55905 |
| 30 | Park Nicollet Methodist Hospital | Saint Louis Park | Minnesota | United States | 55426 |
| 31 | Jackson Heart Clinic | Jackson | Mississippi | United States | 39216 |
| 32 | Saint John's Mercy Heart Health Center | Saint Louis | Missouri | United States | 63131 |
| 33 | Saint Louis Heart and Vascular | Saint Louis | Missouri | United States | 63136 |
| 34 | Cooper University Hospital | Camden | New Jersey | United States | 08103 |
| 35 | Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
| 36 | Robert Wood Johnson University Hospital | New Brunswick | New Jersey | United States | 08901 |
| 37 | Albany Associates in Cardiology | Albany | New York | United States | 12205 |
| 38 | Montefiore Medical Center | Bronx | New York | United States | 10467 |
| 39 | New York University Langone Medical Center | New York | New York | United States | 10016 |
| 40 | Columbia University Medical Center | New York | New York | United States | 10032 |
| 41 | Stony Brook University Hospital and Medical Center | Stony Brook | New York | United States | 11794-8167 |
| 42 | University of North Carolina at Chapel Hill | Chapel Hill | North Carolina | United States | 27599 |
| 43 | The Sanger Clinic, PA | Charlotte | North Carolina | United States | 28203 |
| 44 | Duke University Medical Center | Durham | North Carolina | United States | 27705 |
| 45 | Wake Forest University Health Sciences | Winston-Salem | North Carolina | United States | 27157 |
| 46 | University of Cincinnati Medical Center | Cincinnati | Ohio | United States | 45267 |
| 47 | Cleveland Clinic Foundation | Cleveland | Ohio | United States | 44193 |
| 48 | Ohio State University Medical Center | Columbus | Ohio | United States | 43210 |
| 49 | Oklahoma Heart Institute | Tulsa | Oklahoma | United States | 74104 |
| 50 | Oregon Health and Science University | Portland | Oregon | United States | 97201 |
| 51 | Providence Saint Vincent Medical Center | Portland | Oregon | United States | 97225 |
| 52 | Geisinger Wyoming Valley Medical Center | Danville | Pennsylvania | United States | 17822-2160 |
| 53 | Penn State University Cardiovascular Center | Hershey | Pennsylvania | United States | 17033 |
| 54 | Drexel University College of Medicine | Philadelphia | Pennsylvania | United States | 19102 |
| 55 | University of Pennsylvania Health System | Philadelphia | Pennsylvania | United States | 19104 |
| 56 | V.A. Pittsburgh Healthcare System | Pittsburgh | Pennsylvania | United States | 15240 |
| 57 | Lankenau Hospital | Wynnewood | Pennsylvania | United States | 19096 |
| 58 | Greenville Hospital System University Medical Center | Greenville | South Carolina | United States | 29605 |
| 59 | Memorial Health Care System | Chattanooga | Tennessee | United States | 37404 |
| 60 | Vanderbilt University Medical Center | Nashville | Tennessee | United States | 37232 |
| 61 | Texas Cardiac Arrhythmia | Austin | Texas | United States | 78705 |
| 62 | Baylor Heart and Vascular Hospital | Dallas | Texas | United States | 75226 |
| 63 | Baylor All Saints Medical Center | Fort Worth | Texas | United States | 76104 |
| 64 | University of Texas Health Science Center | Houston | Texas | United States | 77030 |
| 65 | The Heart Hospital Baylor Plano | Plano | Texas | United States | 75093 |
| 66 | South Texas Cardiovascular Consultants | San Antonio | Texas | United States | 78299 |
| 67 | Scott and White Memorial Hospital | Temple | Texas | United States | 76508 |
| 68 | Intermountain Medical Center-LDS Hospital | Salt Lake City | Utah | United States | 84143 |
| 69 | University of Virginia Health System | Charlottesville | Virginia | United States | 22908 |
| 70 | Virginia Hospital Center - Arlington | Falls Church | Virginia | United States | 22042 |
| 71 | Sentara Norfolk General Hospital | Norfolk | Virginia | United States | 23507 |
| 72 | Virginia Commonwealth University Medical Center | Richmond | Virginia | United States | 23219 |
| 73 | Swedish Medical Center - Providence Campus | Seattle | Washington | United States | 98122 |
| 74 | University of Washington Medical Center | Seattle | Washington | United States | 98195 |
| 75 | Cardiac Study Center | Tacoma | Washington | United States | 98405 |
| 76 | Waukesha Memorial Hospital | Waukesha | Wisconsin | United States | 53188 |
| 77 | Royal Adelaide Hospital | Adelaide | South Australia | Australia | 5000 |
| 78 | Royal Melbourne Hospital | Parkville | Victoria | Australia | 3050 |
| 79 | University of Calgary | Calgary | Alberta | Canada | T2N 2T9 |
| 80 | Hamilton Health Sciences | Hamilton | Ontario | Canada | L8L 2X2 |
| 81 | University of Western Ontario - London Health Sciences Centre | London | Ontario | Canada | N6A 5A5 |
| 82 | Southlake Regional Health Centre | Newmarket | Ontario | Canada | L3Y 8C3 |
| 83 | Guangdong Provincial People's Hospital | Guangzhou | Guangdong | China | 510080 |
| 84 | First Affiliated Hospital of Nanjing Medical University | Nanjing | Jiangsu | China | 210029 |
| 85 | First Affiliated Hospital of Dalian Medical University | Dalian | Liaoning | China | 116011 |
| 86 | Beijing Anzhen Hospital | Beijing | China | 100029 | |
| 87 | Fuwai Hospital | Beijing | China | 100037 | |
| 88 | Na Homolce Hospital | Prague 5 | Hlavni Mesto Praha | Czechia | 150 30 |
| 89 | Saint Anne's University Hospital, ICRC | Brno | Czechia | 65691 | |
| 90 | Charles University | Prague 2 | Czechia | 12808 | |
| 91 | Clinic of Cardiology IKEM Medical Institute | Prague 4 | Czechia | 14021 | |
| 92 | University Hospital of Mannheim | Mannheim | Baden-Wurttemberg | Germany | 68167 |
| 93 | Klinikum Coburg | Coburg | Bayern | Germany | 96450 |
| 94 | Universitares Herrzentrum Hamburg | Hamburg | Freie-Hansestadt Hamburg | Germany | 20246 |
| 95 | Herz-und Diabeteszentrum NRW | Bad Oeynhausen | Nordrhein-Westfalen | Germany | D-32545 |
| 96 | Technische Universitat Dresden | Dresden | Saxony | Germany | D-01307 |
| 97 | Kerckhoff Klinik | Bad Nauheim | Germany | D-61231 | |
| 98 | Praxisklinik Herz and GefaBe | Dresden | Germany | 01324 | |
| 99 | CCB - Cardioaniologisches Centrum Bethanien | Frankfurt | Germany | 60431 | |
| 100 | Georg-August-University | Gottingen | Germany | 37075 | |
| 101 | Asklepios Klinik St. Georg | Hamburg | Germany | 20099 | |
| 102 | Asklepios Klinik Barmbek | Hamburg | Germany | 22291 | |
| 103 | Saint Vincentius-Kliniken | Karlsruhe | Germany | 76137 | |
| 104 | Herzzentrum Leipzig | Leipzig | Germany | 04289 | |
| 105 | Universitat Rostock | Rostock | Germany | D-18057 | |
| 106 | Policlinico San Donato Center of Clinical Arrhythmia and Electrophysiology | San Donato Milanese | Lombardia | Italy | 20097 |
| 107 | Policlinico Multimedical Cardiology and Arrhythmia Centre | Milan | Italy | 20099 | |
| 108 | Ospedale di Circolo e Fondazione Macchi | Varese | Italy | 21100 | |
| 109 | Korea University Anam Hospital | Seoul | Korea, Republic of | ||
| 110 | Yonsei University Severance Hospital | Seoul | Korea, Republic of | ||
| 111 | Research Institute of Circulation of Pathology | Novosibirsk | Novosibirskaya Oblast | Russian Federation | 630055 |
| 112 | Clinical Hospital # 83 under the Federal Medical and Biological Agency | Moscow | Russian Federation | 115682 | |
| 113 | Bakoulev Scientific Center for Cardiovascular Surgery | Moscow | Russian Federation | 121552 | |
| 114 | Scientific Research Institute of Cardiology of Ministry of Health of Russian Foundation | Tomsk | Russian Federation | 634012 | |
| 115 | Golden Jubilee Hospital | Glasgow | United Kingdom | G81 4HX | |
| 116 | Saint Bartholomew's Hospital | London | United Kingdom | EC1A 7BE | |
| 117 | Saint George's Hospital Medical School | London | United Kingdom | SW17 0QT | |
| 118 | Saint Mary's Hospital | London | United Kingdom | W2 1NY |
Sponsors and Collaborators
- Mayo Clinic
- National Heart, Lung, and Blood Institute (NHLBI)
- Abbott Medical Devices
- Biosense Webster, Inc.
Investigators
- Principal Investigator: Douglas L. Packer, M.D., Mayo Clinic
- Principal Investigator: Kerry L. Lee, Ph.D., Duke Clinical Research Institute
- Principal Investigator: Daniel B. Mark, M.D., MPH, Duke Clinical Research Institute
- Principal Investigator: Rich A. Robb, Ph.D. Phy, Mayo Clinic
- Study Chair: Yves D. Rosenberg, M.D., MPH, National Heart, Lung, and Blood Institute (NHLBI)
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Douglas L. Packer, MD,
MD,
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00911508
Other Study ID Numbers:
- 09-004616
- U01HL089709
First Posted:
Jun 2, 2009
Last Update Posted:
Apr 21, 2021
Last Verified:
Apr 1, 2021
Keywords provided by Douglas L. Packer, MD,
MD,
Mayo Clinic
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Between November 2009 and April 2016, 2204, patients with atrial fibrillation from 126 sites across 10 countries, were randomized in equal proportions to either catheter ablation or drug therapy, using permuted block randomization with stratification by clinical site. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Left Atrial Ablation | Rate or Rhythm Control Therapy |
|---|---|---|
| Arm/Group Description | All patients randomized to the ablation group were required to undergo left atrial pulmonary vein isolation. The addition of ancillary ablation techniques including linear, ganglion plexus, and electrogram-based approaches were left to the discretion of the investigators. | All patients randomized to drug therapy, were treated with standard rhythm and/or rate control drugs selected in accordance with contemporary guidelines, according to investigator discretion. |
| Period Title: Overall Study | ||
| STARTED | 1108 | 1096 |
| COMPLETED | 1002 | 966 |
| NOT COMPLETED | 106 | 130 |
Baseline Characteristics
| Arm/Group Title | Left Atrial Ablation | Rate or Rhythm Control Therapy | Total |
|---|---|---|---|
| Arm/Group Description | All patients randomized to the ablation group were required to undergo left atrial pulmonary vein isolation. The addition of ancillary ablation techniques including linear, ganglion plexus, and electrogram-based approaches were left to the discretion of the investigators. | All patients randomized to drug therapy, were treated with standard rhythm and/or rate control drugs selected in accordance with contemporary guidelines, according to investigator discretion. | Total of all reporting groups |
| Overall Participants | 1108 | 1096 | 2204 |
| Age, Customized (years) [Median (Inter-Quartile Range) ] | |||
| Age |
68
|
67
|
68
|
| Age, Customized (Count of Participants) | |||
| < 65 years old |
375
33.8%
|
391
35.7%
|
766
34.8%
|
| 65 to <75 years old |
577
52.1%
|
553
50.5%
|
1130
51.3%
|
| ≥ 75 years old |
156
14.1%
|
152
13.9%
|
308
14%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
413
37.3%
|
406
37%
|
819
37.2%
|
| Male |
695
62.7%
|
690
63%
|
1385
62.8%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
3
0.3%
|
1
0.1%
|
4
0.2%
|
| Asian |
42
3.8%
|
42
3.8%
|
84
3.8%
|
| Native Hawaiian or Other Pacific Islander |
1
0.1%
|
1
0.1%
|
2
0.1%
|
| Black or African American |
39
3.5%
|
38
3.5%
|
77
3.5%
|
| White |
1018
91.9%
|
1007
91.9%
|
2025
91.9%
|
| More than one race |
4
0.4%
|
4
0.4%
|
8
0.4%
|
| Unknown or Not Reported |
1
0.1%
|
3
0.3%
|
4
0.2%
|
| Region of Enrollment (Count of Participants) | |||
| Canada |
28
2.5%
|
24
2.2%
|
52
2.4%
|
| South Korea |
8
0.7%
|
10
0.9%
|
18
0.8%
|
| United States |
625
56.4%
|
608
55.5%
|
1233
55.9%
|
| Czechia |
18
1.6%
|
23
2.1%
|
41
1.9%
|
| China |
21
1.9%
|
22
2%
|
43
2%
|
| Italy |
27
2.4%
|
27
2.5%
|
54
2.5%
|
| United Kingdom |
21
1.9%
|
18
1.6%
|
39
1.8%
|
| Australia |
7
0.6%
|
6
0.5%
|
13
0.6%
|
| Germany |
216
19.5%
|
219
20%
|
435
19.7%
|
| Russia |
137
12.4%
|
139
12.7%
|
276
12.5%
|
| Atrial fibrillation type at time of enrollment (Count of Participants) | |||
| Paroxysmal |
470
42.4%
|
476
43.4%
|
946
42.9%
|
| Persistent |
524
47.3%
|
518
47.3%
|
1042
47.3%
|
| Long-standing persistent |
114
10.3%
|
101
9.2%
|
215
9.8%
|
Outcome Measures
| Title | Number of Participants With Composite of Total Mortality, Disabling Stroke, Serious Bleeding, or Cardiac Arrest in Patients Warranting Therapy for AF. |
|---|---|
| Description | All events for each component of the primary endpoint were reviewed and adjudicated in a blinded fashion by an independent clinical events committee using prospectively determined event definitions. Death was defined as all-cause mortality, disabling stroke (including intracranial bleeding) as an irreversible physical limitation defined by a Rankin Stroke Scale ≥2, and serious bleeding as bleeding accompanied by hemodynamic compromise that required surgical intervention or a transfusion of ≥3 units of blood. |
| Time Frame | From date of enrollment until time-to-first event over a median follow-up of 48.5 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Left Atrial Ablation | Rate or Rhythm Control Therapy |
|---|---|---|
| Arm/Group Description | All patients randomized to the ablation group were required to undergo left atrial pulmonary vein isolation. The addition of ancillary ablation techniques including linear, ganglion plexus, and electrogram-based approaches were left to the discretion of the investigators. | All patients randomized to drug therapy, were treated with standard rhythm and/or rate control drugs selected in accordance with contemporary guidelines, according to investigator discretion. |
| Measure Participants | 1108 | 1096 |
| Count of Participants [Participants] |
89
8%
|
101
9.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Left Atrial Ablation, Rate or Rhythm Control Therapy |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 0.86 | |
| Confidence Interval |
(2-Sided) 95% 0.65 to 1.15 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With All-cause Mortality |
|---|---|
| Description | All deaths were reviewed and adjudicated by the Clinical Events Committee |
| Time Frame | From date of enrollment until date of death over a median follow-up of 48.5 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Left Atrial Ablation | Rate or Rhythm Control Therapy |
|---|---|---|
| Arm/Group Description | All patients randomized to the ablation group were required to undergo left atrial pulmonary vein isolation. The addition of ancillary ablation techniques including linear, ganglion plexus, and electrogram-based approaches were left to the discretion of the investigators. | All patients randomized to drug therapy, were treated with standard rhythm and/or rate control drugs selected in accordance with contemporary guidelines, according to investigator discretion. |
| Measure Participants | 1108 | 1096 |
| Count of Participants [Participants] |
58
5.2%
|
67
6.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Left Atrial Ablation, Rate or Rhythm Control Therapy |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 0.85 | |
| Confidence Interval |
(2-Sided) 95% 0.60 to 1.21 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Mortality or Cardiovascular (CV) Hospitalization |
|---|---|
| Description | Hospitalization was characterized by the site principal investigator (PI) and reported as part of the hospitalization case report form. |
| Time Frame | From date of enrollment until time-to-first event of death or CV hospitalization over a median follow-up of 48.5 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Left Atrial Ablation | Rate or Rhythm Control Therapy |
|---|---|---|
| Arm/Group Description | All patients randomized to the ablation group were required to undergo left atrial pulmonary vein isolation. The addition of ancillary ablation techniques including linear, ganglion plexus, and electrogram-based approaches were left to the discretion of the investigators. | All patients randomized to drug therapy, were treated with standard rhythm and/or rate control drugs selected in accordance with contemporary guidelines, according to investigator discretion. |
| Measure Participants | 1108 | 1096 |
| Count of Participants [Participants] |
573
51.7%
|
637
58.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Left Atrial Ablation, Rate or Rhythm Control Therapy |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 0.83 | |
| Confidence Interval |
(2-Sided) 95% 0.74 to 0.93 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Mortality, Disabling Stroke, or CV Hospitalization (for Heart Failure or Acute Ischemic Events) |
|---|---|
| Description | Disabling stroke (including intracranial bleeding) was defined as an irreversible physical limitation defined by a Rankin Stroke Scale ≥2 and the reason for hospitalization was characterized by the site PI and reported as part of the hospitalization case report form. |
| Time Frame | From date of enrollment until time-to-first event of death, stroke, or CV hospitalization (for heart failure or acute ischemic event) over a median follow-up of 48.5 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Left Atrial Ablation | Rate or Rhythm Control Therapy |
|---|---|---|
| Arm/Group Description | All patients randomized to the ablation group were required to undergo left atrial pulmonary vein isolation. The addition of ancillary ablation techniques including linear, ganglion plexus, and electrogram-based approaches were left to the discretion of the investigators. | All patients randomized to drug therapy, were treated with standard rhythm and/or rate control drugs selected in accordance with contemporary guidelines, according to investigator discretion. |
| Measure Participants | 1108 | 1096 |
| Count of Participants [Participants] |
170
15.3%
|
189
17.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Left Atrial Ablation, Rate or Rhythm Control Therapy |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 0.88 | |
| Confidence Interval |
(2-Sided) 95% 0.72 to 1.09 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Cardiovascular Death |
|---|---|
| Description | Cardiovascular death as determined by the Clinical Events Committee based on the available data provided by the Principal Investigator |
| Time Frame | From date of enrollment until date of a cardiovascular death over a median follow-up of 48.5 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Left Atrial Ablation | Rate or Rhythm Control Therapy |
|---|---|---|
| Arm/Group Description | All patients randomized to the ablation group were required to undergo left atrial pulmonary vein isolation. The addition of ancillary ablation techniques including linear, ganglion plexus, and electrogram-based approaches were left to the discretion of the investigators. | All patients randomized to drug therapy, were treated with standard rhythm and/or rate control drugs selected in accordance with contemporary guidelines, according to investigator discretion. |
| Measure Participants | 1108 | 1096 |
| Count of Participants [Participants] |
22
2%
|
23
2.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Left Atrial Ablation, Rate or Rhythm Control Therapy |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 0.94 | |
| Confidence Interval |
(2-Sided) 95% 0.53 to 1.68 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Cardiovascular Death or Disabling Stroke |
|---|---|
| Description | Disabling stroke (including intracranial bleeding) was defined as an irreversible physical limitation defined by a Rankin Stroke Scale ≥2. |
| Time Frame | From date of enrollment until time-to-first event of a cardiovascular death or disabling stroke over a median follow-up of 48.5 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Left Atrial Ablation | Rate or Rhythm Control Therapy |
|---|---|---|
| Arm/Group Description | All patients randomized to the ablation group were required to undergo left atrial pulmonary vein isolation. The addition of ancillary ablation techniques including linear, ganglion plexus, and electrogram-based approaches were left to the discretion of the investigators. | All patients randomized to drug therapy, were treated with standard rhythm and/or rate control drugs selected in accordance with contemporary guidelines, according to investigator discretion. |
| Measure Participants | 1108 | 1096 |
| Count of Participants [Participants] |
24
2.2%
|
27
2.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Left Atrial Ablation, Rate or Rhythm Control Therapy |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 0.87 | |
| Confidence Interval |
(2-Sided) 95% 0.51 to 1.51 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With an Arrhythmic Death or Cardiac Arrest |
|---|---|
| Description | All deaths and cardiac arrest events were adjudicated by the Clinical Events Committee |
| Time Frame | From date of enrollment until time-to-first event for an arrhythmic death or cardiac arrest over a median follow-up of 48.5 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Left Atrial Ablation | Rate or Rhythm Control Therapy |
|---|---|---|
| Arm/Group Description | All patients randomized to the ablation group were required to undergo left atrial pulmonary vein isolation. The addition of ancillary ablation techniques including linear, ganglion plexus, and electrogram-based approaches were left to the discretion of the investigators. | All patients randomized to drug therapy, were treated with standard rhythm and/or rate control drugs selected in accordance with contemporary guidelines, according to investigator discretion. |
| Measure Participants | 1108 | 1096 |
| Count of Participants [Participants] |
10
0.9%
|
13
1.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Left Atrial Ablation, Rate or Rhythm Control Therapy |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 0.76 | |
| Confidence Interval |
(2-Sided) 95% 0.33 to 1.72 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Heart Failure Death |
|---|---|
| Description | All deaths were categorized and adjudicated by the Clinical Events Committee |
| Time Frame | From date of enrollment until date of heart failure death over a median follow-up of 48.5 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Left Atrial Ablation | Rate or Rhythm Control Therapy |
|---|---|---|
| Arm/Group Description | All patients randomized to the ablation group were required to undergo left atrial pulmonary vein isolation. The addition of ancillary ablation techniques including linear, ganglion plexus, and electrogram-based approaches were left to the discretion of the investigators. | All patients randomized to drug therapy, were treated with standard rhythm and/or rate control drugs selected in accordance with contemporary guidelines, according to investigator discretion. |
| Measure Participants | 1108 | 1096 |
| Count of Participants [Participants] |
8
0.7%
|
7
0.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Left Atrial Ablation, Rate or Rhythm Control Therapy |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 1.13 | |
| Confidence Interval |
(2-Sided) 95% 0.41 to 3.09 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants Free From Recurrent Atrial Fibrillation (AF) Following the 90 Day Blanking Period |
|---|---|
| Description | Data from patients using the study provided ECG event recording system were analyzed. A 30-second episode of AF in either group, confirmed through blinded review by an ECG Core Lab Committee was used for defining the endpoint of recurrent AF. |
| Time Frame | From date of therapy initiation until date of first AF recurrence following a 90 day wait (blanking) period over a median follow-up of 48.5 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects were analyzed in the post-blanking period if randomized treatment occurred and the subject did not die, withdraw, or get lost to follow-up before the end of the 90 day blanking period. |
| Arm/Group Title | Left Atrial Ablation | Rate or Rhythm Control Therapy |
|---|---|---|
| Arm/Group Description | All patients randomized to the ablation group were required to undergo left atrial pulmonary vein isolation. The addition of ancillary ablation techniques including linear, ganglion plexus, and electrogram-based approaches were left to the discretion of the investigators. | All patients randomized to drug therapy, were treated with standard rhythm and/or rate control drugs selected in accordance with contemporary guidelines, according to investigator discretion. |
| Measure Participants | 611 | 629 |
| Count of Participants [Participants] |
305
27.5%
|
437
39.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Left Atrial Ablation, Rate or Rhythm Control Therapy |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 0.52 | |
| Confidence Interval |
(2-Sided) 95% 0.45 to 0.60 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Cardiovascular Hospitalization |
|---|---|
| Description | The reason for hospitalization was characterized by the site PI and reported as part of the hospitalization case report form. |
| Time Frame | From date of enrollment until date of cardiovascular hospitalization over a median follow-up of 48.5 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Left Atrial Ablation | Rate or Rhythm Control Therapy |
|---|---|---|
| Arm/Group Description | All patients randomized to the ablation group were required to undergo left atrial pulmonary vein isolation. The addition of ancillary ablation techniques including linear, ganglion plexus, and electrogram-based approaches were left to the discretion of the investigators. | All patients randomized to drug therapy, were treated with standard rhythm and/or rate control drugs selected in accordance with contemporary guidelines, according to investigator discretion. |
| Measure Participants | 1108 | 1096 |
| Count of Participants [Participants] |
556
50.2%
|
605
55.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Left Atrial Ablation, Rate or Rhythm Control Therapy |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 0.86 | |
| Confidence Interval |
(2-Sided) 95% 0.77 to 0.97 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Changes in Quality of Life Measures - AFEQT |
|---|---|
| Description | Atrial Fibrillation Effect on Quality of Life (AFEQT) Overall Score (Scale: 0 = complete disability, 100 = no disability). The AFEQT is a 21-item AF-specific, health-related QOL questionnaire designed to assess the effect of atrial fibrillation on patient quality of life. The AFEQT has an Overall Score (calculated from 18 of the questions) and subscale scores in three domains: symptoms, daily activities, and treatment concern. Overall and subscale scores range from 0 (corresponds to complete disability) to 100 (no AF-related disability). |
| Time Frame | Baseline ,12 month, 5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Only patients with questionnaire data were analyzed. |
| Arm/Group Title | Left Atrial Ablation | Rate or Rhythm Control Therapy |
|---|---|---|
| Arm/Group Description | All patients randomized to the ablation group were required to undergo left atrial pulmonary vein isolation. The addition of ancillary ablation techniques including linear, ganglion plexus, and electrogram-based approaches were left to the discretion of the investigators. | All patients randomized to drug therapy, were treated with standard rhythm and/or rate control drugs selected in accordance with contemporary guidelines, according to investigator discretion. |
| Measure Participants | 1084 | 1078 |
| Baseline |
62.9
(20.5)
|
63.1
(20.6)
|
| 12 Month |
86.4
(16.5)
|
80.9
(18.5)
|
| 5 Year |
86.2
(16.2)
|
83.3
(18.6)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Left Atrial Ablation, Rate or Rhythm Control Therapy |
|---|---|---|
| Comments | 12 Month | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 5.3 | |
| Confidence Interval |
(2-Sided) 95% 3.7 to 6.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Left Atrial Ablation, Rate or Rhythm Control Therapy |
|---|---|---|
| Comments | 5 Years | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 3.4 | |
| Confidence Interval |
(2-Sided) 95% 2.1 to 4.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Changes in Quality of Life Measures - MAFSI Frequency Score |
|---|---|
| Description | The Mayo AF-Specific Symptom Inventory (MAFSI) is a questionnaire comprised of a 10-item AF symptom checklist that asked about both the frequency and severity of each symptom. MAFSI frequency of symptoms over the past month was recorded as 0 (never), 1 (rarely), 2 (sometimes), 3 (often), and 4 (always) for each of the 10 items listed in the questionnaire. The 10 item responses were summed for a total Frequency Score that ranged from 0 (no AF symptoms) to 40 (worst score). |
| Time Frame | Baseline, 12 Month, 5 Year |
Outcome Measure Data
| Analysis Population Description |
|---|
| Only patients with questionnaire data were analyzed. |
| Arm/Group Title | Left Atrial Ablation | Rate or Rhythm Control Therapy |
|---|---|---|
| Arm/Group Description | All patients randomized to the ablation group were required to undergo left atrial pulmonary vein isolation. The addition of ancillary ablation techniques including linear, ganglion plexus, and electrogram-based approaches were left to the discretion of the investigators. | All patients randomized to drug therapy, were treated with standard rhythm and/or rate control drugs selected in accordance with contemporary guidelines, according to investigator discretion. |
| Measure Participants | 1069 | 1061 |
| Baseline |
11.8
(6.2)
|
11.9
(6.4)
|
| 12 Month |
6.4
(6.0)
|
8.1
(6.3)
|
| 5 Year |
5.8
(5.7)
|
7.0
(6.3)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Left Atrial Ablation, Rate or Rhythm Control Therapy |
|---|---|---|
| Comments | 12 Month | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -1.7 | |
| Confidence Interval |
(2-Sided) 95% -2.3 to -1.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Left Atrial Ablation, Rate or Rhythm Control Therapy |
|---|---|---|
| Comments | 5 Year | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -1.4 | |
| Confidence Interval |
(2-Sided) 95% -1.9 to -0.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Changes in Quality of Life Measures - MAFSI Severity Score |
|---|---|
| Description | The Mayo AF-Specific Symptom Inventory (MAFSI) is a questionnaire comprised of a 10-item AF symptom checklist that asked about both the frequency and severity of each symptom. MAFSI severity scores over the past month were recorded as 1 (mild), 2 (moderate), and 3 (extreme) for each of the 10 items listed in the questionnaire. The 10 items items were then summed for the total Severity Score that ranged from 0 (no AF symptoms) to 30 (most severe AF symptoms). |
| Time Frame | Baseline, 12 Month, 5 Year |
Outcome Measure Data
| Analysis Population Description |
|---|
| Only patients with questionnaire data were analyzed. |
| Arm/Group Title | Left Atrial Ablation | Rate or Rhythm Control Therapy |
|---|---|---|
| Arm/Group Description | All patients randomized to the ablation group were required to undergo left atrial pulmonary vein isolation. The addition of ancillary ablation techniques including linear, ganglion plexus, and electrogram-based approaches were left to the discretion of the investigators. | All patients randomized to drug therapy, were treated with standard rhythm and/or rate control drugs selected in accordance with contemporary guidelines, according to investigator discretion. |
| Measure Participants | 1066 | 1056 |
| Baseline |
9.3
(4.9)
|
9.3
(5.1)
|
| 12 Month |
5.0
(4.7)
|
6.5
(5.1)
|
| 5 year |
4.6
(4.7)
|
5.6
(4.9)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Left Atrial Ablation, Rate or Rhythm Control Therapy |
|---|---|---|
| Comments | 12 Month | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -1.5 | |
| Confidence Interval |
(2-Sided) 95% -2.0 to -1.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Left Atrial Ablation, Rate or Rhythm Control Therapy |
|---|---|---|
| Comments | 5 Year | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -1.0 | |
| Confidence Interval |
(2-Sided) 95% -1.7 to -0.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Adverse Events/Complications |
|---|---|
| Description | Comparing individual non-endpoint adverse events between ablative and drug therapy is difficult due to the substantial difference in the types of adverse events expected. Ablation-related events were counted among all patients that were randomized to and received an ablation. Drug-related events were counted among all patients that were randomized to and received drug therapy. |
| Time Frame | From treatment start date to date of event over a median follow-up of 48.5 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Ablation-related events were counted among all patients that were randomized to and received an ablation. Drug-related events were counted among all patients that were randomized to and received drug therapy. |
| Arm/Group Title | Left Atrial Ablation | Rate or Rhythm Control Therapy |
|---|---|---|
| Arm/Group Description | All patients randomized to the ablation group were required to undergo left atrial pulmonary vein isolation. The addition of ancillary ablation techniques including linear, ganglion plexus, and electrogram-based approaches were left to the discretion of the investigators. | All patients randomized to drug therapy, were treated with standard rhythm and/or rate control drugs selected in accordance with contemporary guidelines, according to investigator discretion. |
| Measure Participants | 1006 | 1092 |
| Hyper- or hyopthyroidism |
0
0%
|
17
1.6%
|
| Hypotension |
0
0%
|
3
0.3%
|
| Major proarrhythmic event (VT, VF) |
0
0%
|
9
0.8%
|
| Atrial proarrhythmic event |
0
0%
|
1
0.1%
|
| Allergic reaction |
0
0%
|
7
0.6%
|
| Gastrointestinal abnormality (excluding >moderate) |
0
0%
|
3
0.3%
|
| Liver injury/failure |
0
0%
|
3
0.3%
|
| Pulmonary toxicity |
0
0%
|
1
0.1%
|
| Hematoma |
23
2.1%
|
0
0%
|
| Pseudo aneurysm |
11
1%
|
0
0%
|
| Atrial venous fistula |
4
0.4%
|
0
0%
|
| Pneumothorax |
1
0.1%
|
0
0%
|
| Sepsis |
1
0.1%
|
0
0%
|
| Cardiac tamponade with perforation |
8
0.7%
|
0
0%
|
| Transient ischemic attack (TIA) |
3
0.3%
|
0
0%
|
| Myocardial infarction |
1
0.1%
|
0
0%
|
| Severe pericardial chest pain |
11
1%
|
0
0%
|
| Phrenic nerve injury |
1
0.1%
|
0
0%
|
| Pulmonary vein stenosis >75% |
1
0.1%
|
0
0%
|
| Esophageal ulcer |
5
0.5%
|
0
0%
|
Adverse Events
| Time Frame | Adverse events were collected from time of enrollment through study completion over a median follow-up duration of 48.5 months. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Left Atrial Ablation | Rate or Rhythm Control Therapy | ||
| Arm/Group Description | All patients randomized to the ablation group were required to undergo left atrial pulmonary vein isolation. The addition of ancillary ablation techniques including linear, ganglion plexus, and electrogram-based approaches were left to the discretion of the investigators. | All patients randomized to drug therapy, were treated with standard rhythm and/or rate control drugs selected in accordance with contemporary guidelines, according to investigator discretion. | ||
All Cause Mortality |
||||
| Left Atrial Ablation | Rate or Rhythm Control Therapy | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 58/1108 (5.2%) | 67/1096 (6.1%) | ||
Serious Adverse Events |
||||
| Left Atrial Ablation | Rate or Rhythm Control Therapy | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 454/1108 (41%) | 430/1096 (39.2%) | ||
| Blood and lymphatic system disorders | ||||
| ANAEMIA | 1/1108 (0.1%) | 1 | 5/1096 (0.5%) | 5 |
| ANAEMIA OF MALIGNANT DISEASE | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| AUTOIMMUNE HAEMOLYTIC ANAEMIA | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| FEBRILE NEUTROPENIA | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| HAEMORRHAGIC DISORDER | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| IMMUNE THROMBOCYTOPENIC PURPURA | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| IRON DEFICIENCY ANAEMIA | 1/1108 (0.1%) | 1 | 3/1096 (0.3%) | 3 |
| THROMBOCYTOPENIA | 0/1108 (0%) | 0 | 2/1096 (0.2%) | 2 |
| Cardiac disorders | ||||
| ACUTE CORONARY SYNDROME | 2/1108 (0.2%) | 2 | 1/1096 (0.1%) | 1 |
| ACUTE MYOCARDIAL INFARCTION | 1/1108 (0.1%) | 1 | 2/1096 (0.2%) | 2 |
| ANGINA PECTORIS | 7/1108 (0.6%) | 7 | 5/1096 (0.5%) | 5 |
| ANGINA UNSTABLE | 4/1108 (0.4%) | 4 | 4/1096 (0.4%) | 5 |
| AORTIC VALVE INCOMPETENCE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| AORTIC VALVE STENOSIS | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| ARRHYTHMIA | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| ARTERIOSCLEROSIS CORONARY ARTERY | 0/1108 (0%) | 0 | 2/1096 (0.2%) | 2 |
| ATRIAL FLUTTER | 7/1108 (0.6%) | 7 | 5/1096 (0.5%) | 6 |
| ATRIAL SEPTAL DEFECT ACQUIRED | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| ATRIAL TACHYCARDIA | 6/1108 (0.5%) | 8 | 1/1096 (0.1%) | 2 |
| ATRIAL THROMBOSIS | 2/1108 (0.2%) | 2 | 0/1096 (0%) | 0 |
| ATRIOVENTRICULAR BLOCK | 7/1108 (0.6%) | 7 | 3/1096 (0.3%) | 3 |
| ATRIOVENTRICULAR BLOCK COMPLETE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| ATRIOVENTRICULAR BLOCK SECOND DEGREE | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| BRADYCARDIA | 18/1108 (1.6%) | 18 | 25/1096 (2.3%) | 28 |
| BUNDLE BRANCH BLOCK LEFT | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| CARDIAC ARREST | 10/1108 (0.9%) | 10 | 9/1096 (0.8%) | 10 |
| CARDIAC FAILURE | 60/1108 (5.4%) | 90 | 47/1096 (4.3%) | 77 |
| CARDIAC FAILURE ACUTE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| CARDIAC FAILURE CHRONIC | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| CARDIAC FAILURE CONGESTIVE | 4/1108 (0.4%) | 4 | 3/1096 (0.3%) | 3 |
| CARDIAC PERFORATION | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| CARDIAC TAMPONADE | 10/1108 (0.9%) | 10 | 1/1096 (0.1%) | 1 |
| CARDIAC VALVE DISEASE | 4/1108 (0.4%) | 4 | 5/1096 (0.5%) | 5 |
| CARDIAC VENTRICULAR THROMBOSIS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| CARDIOGENIC SHOCK | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| CARDIOMYOPATHY | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| CORONARY ARTERY DISEASE | 9/1108 (0.8%) | 9 | 3/1096 (0.3%) | 3 |
| CORONARY ARTERY EMBOLISM | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| CORONARY ARTERY OCCLUSION | 4/1108 (0.4%) | 5 | 6/1096 (0.5%) | 7 |
| CORONARY ARTERY STENOSIS | 3/1108 (0.3%) | 3 | 1/1096 (0.1%) | 1 |
| INTRACARDIAC THROMBUS | 5/1108 (0.5%) | 5 | 0/1096 (0%) | 0 |
| LEFT VENTRICULAR DYSFUNCTION | 0/1108 (0%) | 0 | 2/1096 (0.2%) | 2 |
| MITRAL VALVE INCOMPETENCE | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| MITRAL VALVE STENOSIS | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| MYOCARDIAL INFARCTION | 7/1108 (0.6%) | 8 | 18/1096 (1.6%) | 20 |
| MYOCARDIAL ISCHAEMIA | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| MYOCARDITIS | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| PALPITATIONS | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| PERICARDIAL EFFUSION | 22/1108 (2%) | 24 | 3/1096 (0.3%) | 3 |
| PERICARDITIS | 8/1108 (0.7%) | 8 | 2/1096 (0.2%) | 2 |
| PERICARDITIS CONSTRICTIVE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| SINOATRIAL BLOCK | 3/1108 (0.3%) | 3 | 4/1096 (0.4%) | 4 |
| SINUS ARREST | 1/1108 (0.1%) | 1 | 2/1096 (0.2%) | 2 |
| SINUS BRADYCARDIA | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| SINUS NODE DYSFUNCTION | 10/1108 (0.9%) | 10 | 13/1096 (1.2%) | 13 |
| TACHYARRHYTHMIA | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| TACHYCARDIA | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| TACHYCARDIA INDUCED CARDIOMYOPATHY | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| TRICUSPID VALVE DISEASE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| VENTRICULAR ARRHYTHMIA | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| VENTRICULAR EXTRASYSTOLES | 2/1108 (0.2%) | 2 | 2/1096 (0.2%) | 2 |
| VENTRICULAR FIBRILLATION | 2/1108 (0.2%) | 2 | 3/1096 (0.3%) | 3 |
| VENTRICULAR TACHYCARDIA | 11/1108 (1%) | 13 | 9/1096 (0.8%) | 11 |
| Congenital, familial and genetic disorders | ||||
| ATRIAL SEPTAL DEFECT | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| HYDROCELE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| HYPERTROPHIC CARDIOMYOPATHY | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| MUSCULAR DYSTROPHY | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| PATENT DUCTUS ARTERIOSUS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| Ear and labyrinth disorders | ||||
| DEAFNESS | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| DEAFNESS UNILATERAL | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| SUDDEN HEARING LOSS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| TYMPANIC MEMBRANE PERFORATION | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| VERTIGO POSITIONAL | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| VESTIBULAR DISORDER | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| Endocrine disorders | ||||
| HYPERTHYROIDISM | 0/1108 (0%) | 0 | 3/1096 (0.3%) | 3 |
| HYPOTHYROIDISM | 0/1108 (0%) | 0 | 3/1096 (0.3%) | 3 |
| Eye disorders | ||||
| CATARACT | 0/1108 (0%) | 0 | 2/1096 (0.2%) | 2 |
| CATARACT NUCLEAR | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| DIPLOPIA | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| MACULAR FIBROSIS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| OPTIC NERVE DISORDER | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| RETINAL ARTERY OCCLUSION | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| RETINAL DETACHMENT | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| VITREOUS HAEMORRHAGE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| Gastrointestinal disorders | ||||
| ABDOMINAL HERNIA | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| ABDOMINAL HERNIA OBSTRUCTIVE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| ABDOMINAL PAIN | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 2 |
| ABDOMINAL PAIN LOWER | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| ABDOMINAL WALL HAEMATOMA | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| ALCOHOLIC PANCREATITIS | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| COLITIS | 0/1108 (0%) | 0 | 2/1096 (0.2%) | 2 |
| COLITIS ISCHAEMIC | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| CONSTIPATION | 0/1108 (0%) | 0 | 2/1096 (0.2%) | 2 |
| CROHN'S DISEASE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| DIARRHOEA | 3/1108 (0.3%) | 3 | 2/1096 (0.2%) | 2 |
| DUODENAL ULCER | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| DUODENAL ULCER PERFORATION | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| EROSIVE OESOPHAGITIS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| FAECAL INCONTINENCE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| GASTRIC DISORDER | 5/1108 (0.5%) | 5 | 4/1096 (0.4%) | 4 |
| GASTRIC HAEMORRHAGE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| GASTRITIS | 3/1108 (0.3%) | 3 | 1/1096 (0.1%) | 1 |
| GASTROINTESTINAL HAEMORRHAGE | 10/1108 (0.9%) | 10 | 10/1096 (0.9%) | 11 |
| GASTROOESOPHAGEAL REFLUX DISEASE | 1/1108 (0.1%) | 1 | 4/1096 (0.4%) | 4 |
| HAEMATEMESIS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| HAEMORRHOIDAL HAEMORRHAGE | 2/1108 (0.2%) | 2 | 0/1096 (0%) | 0 |
| HAEMORRHOIDS | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| HIATUS HERNIA | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| ILEUS | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| INGUINAL HERNIA | 0/1108 (0%) | 0 | 3/1096 (0.3%) | 3 |
| INGUINAL HERNIA STRANGULATED | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| INTESTINAL HAEMORRHAGE | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 2 |
| INTESTINAL ISCHAEMIA | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| INTESTINAL MASS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| INTESTINAL OBSTRUCTION | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 2 |
| LOWER GASTROINTESTINAL HAEMORRHAGE | 2/1108 (0.2%) | 2 | 4/1096 (0.4%) | 5 |
| MALLORY-WEISS SYNDROME | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| MELAENA | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| NAUSEA | 1/1108 (0.1%) | 2 | 0/1096 (0%) | 0 |
| OESOPHAGEAL DISORDER | 2/1108 (0.2%) | 2 | 1/1096 (0.1%) | 1 |
| OESOPHAGITIS | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| PANCREATIC PSEUDOCYST | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| PANCREATITIS | 1/1108 (0.1%) | 1 | 2/1096 (0.2%) | 2 |
| PANCREATITIS ACUTE | 3/1108 (0.3%) | 3 | 0/1096 (0%) | 0 |
| PANCREATITIS RELAPSING | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| PERITONEAL HAEMORRHAGE | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| PNEUMOPERITONEUM | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| RECTAL HAEMORRHAGE | 3/1108 (0.3%) | 3 | 2/1096 (0.2%) | 2 |
| RECTAL PROLAPSE | 1/1108 (0.1%) | 2 | 0/1096 (0%) | 0 |
| RECTAL ULCER HAEMORRHAGE | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| SMALL INTESTINAL OBSTRUCTION | 2/1108 (0.2%) | 2 | 3/1096 (0.3%) | 3 |
| SMALL INTESTINAL ULCER HAEMORRHAGE | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| SUBILEUS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| TONGUE GEOGRAPHIC | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| UPPER GASTROINTESTINAL HAEMORRHAGE | 1/1108 (0.1%) | 1 | 4/1096 (0.4%) | 4 |
| VOMITING | 6/1108 (0.5%) | 6 | 2/1096 (0.2%) | 2 |
| General disorders | ||||
| ADVERSE DRUG REACTION | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| CARDIAC DEATH | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| CHEST DISCOMFORT | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| CHEST PAIN | 4/1108 (0.4%) | 4 | 2/1096 (0.2%) | 2 |
| DEATH | 14/1108 (1.3%) | 14 | 11/1096 (1%) | 11 |
| DEVICE MALFUNCTION | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| FATIGUE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| GAIT DISTURBANCE | 2/1108 (0.2%) | 3 | 2/1096 (0.2%) | 2 |
| HERNIA | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| IMPAIRED HEALING | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| MEDICAL DEVICE COMPLICATION | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| NON-CARDIAC CHEST PAIN | 4/1108 (0.4%) | 5 | 4/1096 (0.4%) | 4 |
| PAIN | 1/1108 (0.1%) | 1 | 4/1096 (0.4%) | 4 |
| PYREXIA | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| STENT-GRAFT ENDOLEAK | 0/1108 (0%) | 0 | 2/1096 (0.2%) | 2 |
| Hepatobiliary disorders | ||||
| ACUTE HEPATIC FAILURE | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| BILE DUCT STONE | 2/1108 (0.2%) | 2 | 1/1096 (0.1%) | 1 |
| CHOLECYSTITIS | 5/1108 (0.5%) | 5 | 1/1096 (0.1%) | 1 |
| CHOLECYSTITIS ACUTE | 2/1108 (0.2%) | 2 | 0/1096 (0%) | 0 |
| CHOLELITHIASIS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| CHRONIC HEPATITIS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| HEPATIC CIRRHOSIS | 1/1108 (0.1%) | 1 | 2/1096 (0.2%) | 2 |
| HEPATIC FAILURE | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| NON-ALCOHOLIC STEATOHEPATITIS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| Immune system disorders | ||||
| ANAPHYLACTIC SHOCK | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| HYPERSENSITIVITY | 1/1108 (0.1%) | 1 | 3/1096 (0.3%) | 3 |
| Infections and infestations | ||||
| ABSCESS LIMB | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| ABSCESS SOFT TISSUE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| ANAL ABSCESS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| ANORECTAL INFECTION | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| APPENDICITIS | 1/1108 (0.1%) | 2 | 3/1096 (0.3%) | 3 |
| BACTERAEMIA | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| BRONCHITIS | 2/1108 (0.2%) | 2 | 1/1096 (0.1%) | 1 |
| CELLULITIS | 7/1108 (0.6%) | 7 | 3/1096 (0.3%) | 3 |
| CHOLECYSTITIS INFECTIVE | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| DEVICE RELATED INFECTION | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 2 |
| DIABETIC FOOT INFECTION | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| DIABETIC GANGRENE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| DIVERTICULITIS | 3/1108 (0.3%) | 3 | 6/1096 (0.5%) | 7 |
| ERYSIPELAS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| GASTROENTERITIS | 2/1108 (0.2%) | 2 | 2/1096 (0.2%) | 2 |
| GASTROENTERITIS CLOSTRIDIAL | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| GASTROENTERITIS VIRAL | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| HAEMOPHILUS INFECTION | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| INFECTION | 11/1108 (1%) | 11 | 10/1096 (0.9%) | 11 |
| INFLUENZA | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| LUNG ABSCESS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| LYME DISEASE | 0/1108 (0%) | 0 | 2/1096 (0.2%) | 2 |
| MEDICAL DEVICE SITE INFECTION | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| NASOPHARYNGITIS | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| OSTEOMYELITIS | 2/1108 (0.2%) | 2 | 0/1096 (0%) | 0 |
| PNEUMONIA | 32/1108 (2.9%) | 37 | 29/1096 (2.6%) | 34 |
| PNEUMONIA BACTERIAL | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| POST PROCEDURAL CELLULITIS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| POSTOPERATIVE WOUND INFECTION | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| PULMONARY TUBERCULOSIS | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| PYELONEPHRITIS | 3/1108 (0.3%) | 3 | 1/1096 (0.1%) | 1 |
| SALMONELLA BACTERAEMIA | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| SALMONELLOSIS | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| SEPSIS | 11/1108 (1%) | 12 | 11/1096 (1%) | 12 |
| SEPTIC SHOCK | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| STAPHYLOCOCCAL BACTERAEMIA | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| STAPHYLOCOCCAL INFECTION | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| STREPTOCOCCAL BACTERAEMIA | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| STREPTOCOCCAL SEPSIS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| UPPER RESPIRATORY TRACT INFECTION | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| URINARY TRACT INFECTION | 12/1108 (1.1%) | 12 | 10/1096 (0.9%) | 10 |
| UROSEPSIS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| VULVAL ABSCESS | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| ACCIDENTAL OVERDOSE | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| ANASTOMOTIC LEAK | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| ANKLE FRACTURE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| BRAIN CONTUSION | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| BURN OESOPHAGEAL | 5/1108 (0.5%) | 5 | 0/1096 (0%) | 0 |
| CONCUSSION | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| CONTRAST MEDIA REACTION | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| CONTUSION | 1/1108 (0.1%) | 2 | 0/1096 (0%) | 0 |
| CRANIOCEREBRAL INJURY | 2/1108 (0.2%) | 2 | 1/1096 (0.1%) | 1 |
| FALL | 7/1108 (0.6%) | 9 | 1/1096 (0.1%) | 1 |
| FEMORAL NECK FRACTURE | 1/1108 (0.1%) | 1 | 2/1096 (0.2%) | 2 |
| FEMUR FRACTURE | 1/1108 (0.1%) | 1 | 2/1096 (0.2%) | 3 |
| FIBULA FRACTURE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| FOOT FRACTURE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| GUN SHOT WOUND | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| HAND FRACTURE | 2/1108 (0.2%) | 2 | 0/1096 (0%) | 0 |
| HEAD INJURY | 2/1108 (0.2%) | 2 | 0/1096 (0%) | 0 |
| HEAT EXHAUSTION | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| HIP FRACTURE | 3/1108 (0.3%) | 3 | 1/1096 (0.1%) | 1 |
| HUMERUS FRACTURE | 2/1108 (0.2%) | 2 | 1/1096 (0.1%) | 1 |
| INCISIONAL HERNIA | 0/1108 (0%) | 0 | 3/1096 (0.3%) | 3 |
| INJURY | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| LACERATION | 0/1108 (0%) | 0 | 2/1096 (0.2%) | 2 |
| MENTAL STATUS CHANGES POSTOPERATIVE | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| NERVE INJURY | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| PATELLA FRACTURE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| PELVIC FRACTURE | 2/1108 (0.2%) | 2 | 0/1096 (0%) | 0 |
| POST CONCUSSION SYNDROME | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| POST PROCEDURAL COMPLICATION | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| POST PROCEDURAL HAEMORRHAGE | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| POSTOPERATIVE ILEUS | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| RADIATION SKIN INJURY | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| RADIUS FRACTURE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| RIB FRACTURE | 4/1108 (0.4%) | 4 | 0/1096 (0%) | 0 |
| ROAD TRAFFIC ACCIDENT | 1/1108 (0.1%) | 1 | 2/1096 (0.2%) | 2 |
| SPINAL COMPRESSION FRACTURE | 1/1108 (0.1%) | 1 | 2/1096 (0.2%) | 2 |
| SPLENIC RUPTURE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| SUBDURAL HAEMATOMA | 11/1108 (1%) | 11 | 2/1096 (0.2%) | 3 |
| TENDON RUPTURE | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| THORACIC VERTEBRAL FRACTURE | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| TIBIA FRACTURE | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| TOXICITY TO VARIOUS AGENTS | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| TRAUMATIC HAEMATOMA | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| VASCULAR PSEUDOANEURYSM | 11/1108 (1%) | 11 | 3/1096 (0.3%) | 3 |
| WOUND | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| WRIST FRACTURE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| Investigations | ||||
| ANTICOAGULATION DRUG LEVEL ABOVE THERAPEUTIC | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| BLOOD BICARBONATE DECREASED | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| BODY TEMPERATURE INCREASED | 0/1108 (0%) | 0 | 3/1096 (0.3%) | 3 |
| ELECTROCARDIOGRAM QT PROLONGED | 2/1108 (0.2%) | 2 | 1/1096 (0.1%) | 1 |
| INTERNATIONAL NORMALISED RATIO ABNORMAL | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| LIVER FUNCTION TEST ABNORMAL | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| Metabolism and nutrition disorders | ||||
| DEHYDRATION | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| DIABETES MELLITUS | 2/1108 (0.2%) | 2 | 1/1096 (0.1%) | 1 |
| DIABETES MELLITUS INADEQUATE CONTROL | 0/1108 (0%) | 0 | 2/1096 (0.2%) | 2 |
| DIABETIC KETOACIDOSIS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| FAILURE TO THRIVE | 1/1108 (0.1%) | 1 | 2/1096 (0.2%) | 2 |
| FLUID OVERLOAD | 10/1108 (0.9%) | 10 | 5/1096 (0.5%) | 5 |
| GOUT | 3/1108 (0.3%) | 3 | 1/1096 (0.1%) | 1 |
| HYPERGLYCAEMIA | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| HYPOGLYCAEMIA | 1/1108 (0.1%) | 1 | 2/1096 (0.2%) | 3 |
| HYPOKALAEMIA | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| HYPONATRAEMIA | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| MALNUTRITION | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| METABOLIC ACIDOSIS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| OBESITY | 0/1108 (0%) | 0 | 2/1096 (0.2%) | 2 |
| TYPE 2 DIABETES MELLITUS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| ARTHRITIS | 3/1108 (0.3%) | 4 | 2/1096 (0.2%) | 2 |
| BACK PAIN | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| BONE DISORDER | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| BURSITIS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| CHONDROCALCINOSIS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| CHONDROCALCINOSIS PYROPHOSPHATE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| CHONDROPATHY | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| COSTOCHONDRITIS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| GOUTY ARTHRITIS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| GOUTY TOPHUS | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| HAEMARTHROSIS | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 2 |
| INTERVERTEBRAL DISC PROTRUSION | 1/1108 (0.1%) | 1 | 2/1096 (0.2%) | 2 |
| MUSCLE DISORDER | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| MUSCULAR WEAKNESS | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| MUSCULOSKELETAL CHEST PAIN | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| MUSCULOSKELETAL PAIN | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| NECK PAIN | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| OSTEOARTHRITIS | 18/1108 (1.6%) | 21 | 24/1096 (2.2%) | 28 |
| OSTEOCHONDROSIS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| OSTEOPOROTIC FRACTURE | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| PAIN IN EXTREMITY | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| RHEUMATOID ARTHRITIS | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| ROTATOR CUFF SYNDROME | 2/1108 (0.2%) | 2 | 2/1096 (0.2%) | 2 |
| SCLERODERMA | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| SCOLIOSIS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| SPINAL COLUMN STENOSIS | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 2 |
| SPONDYLOLISTHESIS | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| ACUTE MYELOID LEUKAEMIA | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| ANOGENITAL WARTS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| APPENDIX CANCER | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| B-CELL LYMPHOMA | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| BASAL CELL CARCINOMA | 3/1108 (0.3%) | 3 | 2/1096 (0.2%) | 3 |
| BLADDER CANCER | 2/1108 (0.2%) | 2 | 1/1096 (0.1%) | 1 |
| BLADDER NEOPLASM | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| BLADDER TRANSITIONAL CELL CARCINOMA | 2/1108 (0.2%) | 2 | 0/1096 (0%) | 0 |
| BLADDER TRANSITIONAL CELL CARCINOMA RECURRENT | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| BRAIN CANCER METASTATIC | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| BREAST CANCER | 1/1108 (0.1%) | 1 | 2/1096 (0.2%) | 2 |
| CHOLANGIOCARCINOMA | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| CHOLESTEATOMA | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| CHRONIC LYMPHOCYTIC LEUKAEMIA | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| CHRONIC MYELOID LEUKAEMIA | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| COLON ADENOMA | 1/1108 (0.1%) | 1 | 2/1096 (0.2%) | 2 |
| COLON CANCER | 1/1108 (0.1%) | 1 | 2/1096 (0.2%) | 2 |
| DIFFUSE LARGE B-CELL LYMPHOMA | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| GASTRIC CANCER | 1/1108 (0.1%) | 2 | 0/1096 (0%) | 0 |
| INVASIVE LOBULAR BREAST CARCINOMA | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| LARGE INTESTINE BENIGN NEOPLASM | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| LIPOMA | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| LUNG ADENOCARCINOMA | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| LUNG CANCER METASTATIC | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| LUNG CARCINOMA CELL TYPE UNSPECIFIED RECURRENT | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| LUNG CARCINOMA CELL TYPE UNSPECIFIED STAGE III | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| LUNG NEOPLASM MALIGNANT | 3/1108 (0.3%) | 3 | 6/1096 (0.5%) | 6 |
| LYMPHOMA | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| MALIGNANT MELANOMA | 2/1108 (0.2%) | 2 | 2/1096 (0.2%) | 2 |
| MALIGNANT PERITONEAL NEOPLASM | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| METASTASES TO LIVER | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| METASTASES TO LUNG | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| METASTATIC GASTRIC CANCER | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| METASTATIC MALIGNANT MELANOMA | 0/1108 (0%) | 0 | 2/1096 (0.2%) | 2 |
| METASTATIC NEOPLASM | 2/1108 (0.2%) | 3 | 0/1096 (0%) | 0 |
| MYELODYSPLASTIC SYNDROME | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| NEUROENDOCRINE CARCINOMA METASTATIC | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| NON-SMALL CELL LUNG CANCER | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| OESOPHAGEAL ADENOCARCINOMA | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| OESOPHAGEAL CARCINOMA | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 2 |
| OVARIAN ADENOMA | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| PANCREATIC CARCINOMA | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| PLASMA CELL MYELOMA | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| PROSTATE CANCER | 6/1108 (0.5%) | 6 | 4/1096 (0.4%) | 4 |
| PROSTATE CANCER METASTATIC | 0/1108 (0%) | 0 | 2/1096 (0.2%) | 2 |
| PROSTATE CANCER STAGE III | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| RECTAL CANCER | 0/1108 (0%) | 0 | 2/1096 (0.2%) | 2 |
| RENAL CANCER | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| SALIVARY GLAND NEOPLASM | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| SQUAMOUS CELL CARCINOMA | 3/1108 (0.3%) | 6 | 1/1096 (0.1%) | 1 |
| SQUAMOUS CELL CARCINOMA OF SKIN | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| SQUAMOUS CELL CARCINOMA OF THE ORAL CAVITY | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| THROAT CANCER | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| THYROID ADENOMA | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| TRANSITIONAL CELL CARCINOMA | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| Nervous system disorders | ||||
| ALTERED STATE OF CONSCIOUSNESS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| CAROTID ARTERIOSCLEROSIS | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| CAROTID ARTERY OCCLUSION | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| CAROTID ARTERY STENOSIS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| CARPAL TUNNEL SYNDROME | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| CEREBRAL HAEMORRHAGE | 0/1108 (0%) | 0 | 2/1096 (0.2%) | 2 |
| CEREBROVASCULAR ACCIDENT | 22/1108 (2%) | 22 | 33/1096 (3%) | 39 |
| CERVICAL MYELOPATHY | 0/1108 (0%) | 0 | 2/1096 (0.2%) | 2 |
| DEMENTIA | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| DEMENTIA ALZHEIMER'S TYPE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| DIZZINESS | 7/1108 (0.6%) | 7 | 8/1096 (0.7%) | 8 |
| DYSARTHRIA | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| ENCEPHALOPATHY | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| EPILEPSY | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 2 |
| HAEMORRHAGE INTRACRANIAL | 3/1108 (0.3%) | 3 | 2/1096 (0.2%) | 2 |
| HAEMORRHAGIC STROKE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| HYPERTONIA | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| METABOLIC ENCEPHALOPATHY | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| MYELOPATHY | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| NERVOUS SYSTEM DISORDER | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| PARKINSON'S DISEASE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| PHRENIC NERVE PARALYSIS | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| POLYNEUROPATHY | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| POST-INJECTION DELIRIUM SEDATION SYNDROME | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| PRESYNCOPE | 0/1108 (0%) | 0 | 2/1096 (0.2%) | 2 |
| RADICULOPATHY | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| SCIATICA | 0/1108 (0%) | 0 | 2/1096 (0.2%) | 2 |
| SEIZURE | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| SPINAL CORD DISORDER | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| SPINAL CORD HAEMORRHAGE | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| SUBARACHNOID HAEMORRHAGE | 3/1108 (0.3%) | 3 | 2/1096 (0.2%) | 2 |
| SYNCOPE | 15/1108 (1.4%) | 17 | 19/1096 (1.7%) | 22 |
| TRANSIENT ISCHAEMIC ATTACK | 20/1108 (1.8%) | 20 | 19/1096 (1.7%) | 21 |
| TRIGEMINAL NEURITIS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| UNRESPONSIVE TO STIMULI | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| VIITH NERVE PARALYSIS | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| Product Issues | ||||
| DEVICE BATTERY ISSUE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| DEVICE DAMAGE | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| DEVICE DISLOCATION | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| DEVICE INAPPROPRIATE SHOCK DELIVERY | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| DEVICE ISSUE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| DEVICE OCCLUSION | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| THROMBOSIS IN DEVICE | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| Psychiatric disorders | ||||
| ANXIETY | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| COMPLETED SUICIDE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| DELIRIUM | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| MAJOR DEPRESSION | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| MENTAL STATUS CHANGES | 1/1108 (0.1%) | 1 | 2/1096 (0.2%) | 2 |
| SUICIDE ATTEMPT | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| Renal and urinary disorders | ||||
| ACUTE KIDNEY INJURY | 2/1108 (0.2%) | 2 | 2/1096 (0.2%) | 2 |
| CALCULUS BLADDER | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| CALCULUS URETERIC | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| HAEMATURIA | 2/1108 (0.2%) | 2 | 5/1096 (0.5%) | 5 |
| HYDRONEPHROSIS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| NEPHROLITHIASIS | 0/1108 (0%) | 0 | 3/1096 (0.3%) | 3 |
| NEPHROTIC SYNDROME | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| RENAL ARTERY STENOSIS | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| RENAL COLIC | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| RENAL FAILURE | 16/1108 (1.4%) | 18 | 9/1096 (0.8%) | 10 |
| RENAL HAEMORRHAGE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| RENAL IMPAIRMENT | 1/1108 (0.1%) | 1 | 3/1096 (0.3%) | 3 |
| RENAL MASS | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| TUBULOINTERSTITIAL NEPHRITIS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| URETEROLITHIASIS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| URETHRAL CYST | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| URETHRAL STENOSIS | 0/1108 (0%) | 0 | 2/1096 (0.2%) | 4 |
| URINARY INCONTINENCE | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| URINARY RETENTION | 2/1108 (0.2%) | 2 | 1/1096 (0.1%) | 1 |
| Reproductive system and breast disorders | ||||
| BENIGN PROSTATIC HYPERPLASIA | 3/1108 (0.3%) | 3 | 1/1096 (0.1%) | 1 |
| FEMALE GENITAL TRACT FISTULA | 0/1108 (0%) | 0 | 2/1096 (0.2%) | 2 |
| OVARIAN MASS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| PELVIC FLUID COLLECTION | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| POSTMENOPAUSAL HAEMORRHAGE | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| PROSTATOMEGALY | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| VAGINAL HAEMORRHAGE | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| ACUTE RESPIRATORY DISTRESS SYNDROME | 2/1108 (0.2%) | 2 | 1/1096 (0.1%) | 1 |
| ACUTE RESPIRATORY FAILURE | 2/1108 (0.2%) | 2 | 0/1096 (0%) | 0 |
| ASTHMA | 2/1108 (0.2%) | 8 | 4/1096 (0.4%) | 6 |
| CHRONIC OBSTRUCTIVE PULMONARY DISEASE | 3/1108 (0.3%) | 3 | 5/1096 (0.5%) | 5 |
| CHRONIC RESPIRATORY FAILURE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| DYSPHONIA | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| DYSPNOEA | 9/1108 (0.8%) | 9 | 11/1096 (1%) | 12 |
| DYSPNOEA EXERTIONAL | 0/1108 (0%) | 0 | 2/1096 (0.2%) | 2 |
| EPISTAXIS | 2/1108 (0.2%) | 2 | 1/1096 (0.1%) | 1 |
| HAEMOPTYSIS | 2/1108 (0.2%) | 2 | 0/1096 (0%) | 0 |
| HAEMOTHORAX | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| INTERSTITIAL LUNG DISEASE | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| PLEURAL EFFUSION | 8/1108 (0.7%) | 12 | 9/1096 (0.8%) | 9 |
| PLEURITIC PAIN | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| PNEUMOTHORAX | 3/1108 (0.3%) | 3 | 1/1096 (0.1%) | 1 |
| PULMONARY CONGESTION | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| PULMONARY EMBOLISM | 4/1108 (0.4%) | 4 | 5/1096 (0.5%) | 5 |
| PULMONARY FIBROSIS | 0/1108 (0%) | 0 | 2/1096 (0.2%) | 2 |
| PULMONARY HYPERTENSION | 1/1108 (0.1%) | 2 | 1/1096 (0.1%) | 1 |
| PULMONARY MASS | 2/1108 (0.2%) | 2 | 1/1096 (0.1%) | 1 |
| PULMONARY OEDEMA | 8/1108 (0.7%) | 8 | 3/1096 (0.3%) | 3 |
| PULMONARY TOXICITY | 1/1108 (0.1%) | 1 | 2/1096 (0.2%) | 2 |
| PULMONARY VEIN STENOSIS | 2/1108 (0.2%) | 2 | 0/1096 (0%) | 0 |
| RESPIRATORY DEPRESSION | 2/1108 (0.2%) | 2 | 2/1096 (0.2%) | 2 |
| RESPIRATORY DISTRESS | 0/1108 (0%) | 0 | 2/1096 (0.2%) | 2 |
| RESPIRATORY FAILURE | 3/1108 (0.3%) | 4 | 4/1096 (0.4%) | 4 |
| SLEEP APNOEA SYNDROME | 4/1108 (0.4%) | 4 | 3/1096 (0.3%) | 6 |
| WHEEZING | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| ANGIOEDEMA | 2/1108 (0.2%) | 2 | 0/1096 (0%) | 0 |
| DIABETIC FOOT | 2/1108 (0.2%) | 3 | 0/1096 (0%) | 0 |
| ERYTHEMA | 2/1108 (0.2%) | 2 | 0/1096 (0%) | 0 |
| Surgical and medical procedures | ||||
| CYTOREDUCTIVE SURGERY | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| HERNIA REPAIR | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| HIP ARTHROPLASTY | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| IMPLANTABLE DEFIBRILLATOR REMOVAL | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| IMPLANTABLE DEFIBRILLATOR REPLACEMENT | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| Vascular disorders | ||||
| AORTIC ANEURYSM | 2/1108 (0.2%) | 2 | 1/1096 (0.1%) | 1 |
| AORTIC ANEURYSM RUPTURE | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| AORTIC DILATATION | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| AORTIC OCCLUSION | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| AORTIC STENOSIS | 4/1108 (0.4%) | 4 | 1/1096 (0.1%) | 1 |
| ARTERIOSCLEROSIS | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| ARTERIOVENOUS FISTULA | 2/1108 (0.2%) | 2 | 0/1096 (0%) | 0 |
| DEEP VEIN THROMBOSIS | 2/1108 (0.2%) | 2 | 1/1096 (0.1%) | 1 |
| EMBOLISM | 2/1108 (0.2%) | 2 | 4/1096 (0.4%) | 4 |
| GRANULOMATOSIS WITH POLYANGIITIS | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| HAEMATOMA | 17/1108 (1.5%) | 17 | 3/1096 (0.3%) | 3 |
| HAEMORRHAGE | 7/1108 (0.6%) | 9 | 9/1096 (0.8%) | 9 |
| HYPERTENSION | 7/1108 (0.6%) | 8 | 10/1096 (0.9%) | 10 |
| HYPERTENSIVE CRISIS | 9/1108 (0.8%) | 10 | 11/1096 (1%) | 14 |
| HYPOTENSION | 8/1108 (0.7%) | 8 | 2/1096 (0.2%) | 2 |
| INTERMITTENT CLAUDICATION | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| ISCHAEMIA | 5/1108 (0.5%) | 6 | 10/1096 (0.9%) | 10 |
| LYMPHATIC FISTULA | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| ORTHOSTATIC HYPOTENSION | 2/1108 (0.2%) | 2 | 1/1096 (0.1%) | 1 |
| PERIPHERAL ARTERIAL OCCLUSIVE DISEASE | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| PERIPHERAL ARTERY ANEURYSM | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| PERIPHERAL ARTERY THROMBOSIS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
| PERIPHERAL EMBOLISM | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| PERIPHERAL VENOUS DISEASE | 1/1108 (0.1%) | 1 | 1/1096 (0.1%) | 1 |
| VASCULAR STENOSIS | 1/1108 (0.1%) | 1 | 0/1096 (0%) | 0 |
| VASCULITIS | 0/1108 (0%) | 0 | 1/1096 (0.1%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| Left Atrial Ablation | Rate or Rhythm Control Therapy | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/1108 (0%) | 0/1096 (0%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Study has been designed as a multicenter study and the data generated from Institution/PI's evaluation may not be sufficient to draw meaningful conclusions. Thus, Institution/PI shall not individually publish the results of the Study.
Results Point of Contact
| Name/Title | Dr. Douglas L. Packer |
|---|---|
| Organization | Mayo Clinic |
| Phone | 507-255-6263 |
| CABANA@mayo.edu |
Responsible Party:
Douglas L. Packer, MD,
MD,
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00911508
Other Study ID Numbers:
- 09-004616
- U01HL089709
First Posted:
Jun 2, 2009
Last Update Posted:
Apr 21, 2021
Last Verified:
Apr 1, 2021