Persistent Atrial Fibrillation
Conditions
Keywords
Atrial Fibrillation, Convergent Procedure, Combined Epicardial/ Endocardial Ablation, Hybrid Procedure, Radiofrequency Ablation, Arrhythmia, RF Ablation
Brief summary
This is a multi-center, open label, randomized pivotal study evaluating the safety and efficacy of the EPi-Sense-AF Guided Coagulation System for the treatment of persistent AF patients, refractory or intolerant to at least one Class I and/or III Anti Arrhythmic Drug (AAD).
Detailed description
The objective of this randomized pivotal study is to evaluate the safety and efficacy of the AtriCure EPi-Sense®-AF Guided Coagulation System with VisiTrax® for the treatment of symptomatic persistent Atrial Fibrillation (AF) patients, refractory or intolerant to at least one Class I or Class III anti-arrhythmic drug (AAD). 153 subjects from up to 27 US and 3 OUS sites. Randomized 2:1. The primary efficacy endpoint is success or failure to be AF/AT/AFL free absent class I and III AADs except for a previously failed or intolerant class I or III AAD with no increase in dosage following the 3-month blanking period through the 12-month post procedure follow-up visit. The primary safety endpoint is the incidence of major adverse events (MAEs) listed in the protocol for subjects undergoing the convergent procedure for the procedural to 30-day post procedure time period.
Interventions
DEVICEAtriCure EPi-Sense-AF Guided Coagulation System with VisiTrax
Convergent Epicardial Endocardial Ablation Procedure
DEVICEEndocardial RF Catheter ablation using Open Irrigated-tip RF Abaltion Catheter with unidirectional or bidirectional steering
Endocardial Catheter Ablation Procedure
Sponsors
AtriCure, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
2:1 randomized (Convergent Procedure versus standalone endocardial catheter ablation) multi-center pivotal clinical study
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age \> 18 years; \< 80 years * Left atrium \< 6.0 cm * Refractory or intolerant to one AAD (class I and/or III) * Documentation of persistent AF * Provided written informed consent
Exclusion criteria
* Patients requiring concomitant surgery * Left ventricular ejection fraction \< 40% * Pregnant or planning to become pregnant during study * Co-morbid medical conditions that limit one year life expectancy * Previous cardiac surgery * History of pericarditis * Previous cerebrovascular accident (CVA), excluding fully resolved transient Ischemic attack (TIA) * Patients who have active infection or sepsis * Patients with esophageal ulcers strictures and varices * Patients with renal dysfunction who are not on dialysis * Patients who are contraindicated for anticoagulants * Patients who are being treated for ventricular arrhythmias * Patients who have had a previous left atrial catheter ablation for AF * Patients with existing Implantable Cardioverter-Defibrillator (ICDs) * Current participation in another clinical investigation of a medical device or a drug, or recent participation in such a study within 30 days prior to study enrollment * Not competent to legally represent him or herself
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Efficacy Endpoint - Number of Participants to Achieve Freedom From AF/AT/AFL. | 12 Months | This binary primary endpoint measures number of patients to achieve freedom from AF/AT/AFL absent class I and III AADs except for previously failed or intolerant I or III AAD with no increase in dosage following the 3-month blanking period through the 12 months post procedure follow-up visit will be compared between the two treatment groups using a chi-square test using a two-sided alpha of .05 to determine if superiority of the treatment arm is attained. |
| Primary Safety Analysis | 30 days | The primary safety analysis will measure the number of Major Adverse Events (MAE) collected from the start of the coagulation procedure to 30 days post procedure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AF Freedom Through 12 Months- Absent of an Increased Dose or New Class I/III AAD's. | 12 Months | Number of patients with AF Freedom through 12 Months (ITT Population) absent of an increased dose or new class I/III AAD's |
| Number of Subjects With AF Burden Reduction of at Least 90% at 12 Months Relative to Baseline, Regardless of Class I/III AADs. | 12 Months | Number of subjects with AF freedom through 12 months achieved in the EPi-Sense group compared to subjects in the Catheter Ablation group. |
| Change in Atrial Fibrillation Severity Scale (AFSS) | 12 months | Change was calculated as the value at 12 months minus the value at baseline. The University of Toronto's Atrial Fibrillation Severity Scale (AFSS) is a composite score of overall subject-perceived severity, global well-being, atrial fibrillation frequency, and atrial fibrillation duration. The score ranges from 3 to 30, with higher scores indicating greater atrial fibrillation burden. |
| Secondary Safety Endpoint - Serious Adverse Events Through 12 Months Post-procedure. | 12 month | The secondary safety endpoint for the study was the number of participants with serious adverse events (SAEs) in the study through the 12-months post-procedure. |
| Quality of Life-Change in SF-36 Mental Health Composite Score Using Short Form Survey (SF-36) | 12 months | Change was calculated as the value at 12 months minus the value at baseline. The 36-Item Short Form Health Survey (SF-36) is used to determine a mental composite score based on the following subscales: general mental health (psychological distress and well-being); limitations in usual role activities because of emotional problems; and general health perceptions. The subscale scores are transformed into a range from 0 to 100, with 0=worst HRQL, 100=best HRQL. The physical and mental component scores are constructed as a T-score with a mean of 50 and standard deviation of 10 and no minimum or maximum score, with higher scores indicating better health status. |
| Change in 6-Minute Walk Score | 12 months | 6 minute walk score was measured by change from baseline compared to 12-months post-procedure between the EPi-Sense and Catheter Ablation groups. |
| Change in Left Atrial Diameter | 6 Months | Change in Left Atrial Diameter at 6 months from baseline. |
| Change in Quality of Life Physical Health Composite Scores Using Short Form Health Survey (SF-36) | 12 Months | Change was calculated as the value at 12 months minus the value at baseline. The 36-Item Short Form Health Survey (SF-36) is used to determine a physical composite score based on following subscales: limitations in physical activities because of health problems; limitations in usual role activities because of physical health problems; bodily pain; vitality (energy and fatigue); and general health perceptions. The subscale scores are transformed into a range from 0 to 100, with 0=worst HRQL, 100=best HRQL. The physical component scores are constructed as a T-score with a mean of 50 and standard deviation of 10 and no minimum or maximum score, with higher scores indicating better health status. |
| Number of Patients With AF Burden Reduction of at Least 90% at 12 Months Compared to Baseline | 12 Months | AF Burden Reduction of at Least 90% at 12-Months (ITT Population): The first secondary effectiveness endpoint in the fixed-sequence testing was defined as at least 90% reduction in AF burden, absent of an increased dose or new class I/III AADs, at 12 months compared to baseline. |
Countries
United Kingdom, United States
Participant flow
Recruitment details
Recruiting for the CONVERGE Study began with first site IRB approval Nov 13, 2013. Recruiting locations included physician offices, clinics and site clinical study offices. * The first milestone for recruiting purposes was the first 25 patients treated. This milestone was reached July 06, 2015. * Milestone two was hit with the attainment of 50 patients treated on September 28, 2016 * The third milestone was the approval of the total cohort of 153 patients by the FDA on November 17, 2017.
Pre-assignment details
10 subjects were consented but withdrew prior to assignment to a treatment arm. 5 subjects were excluded by Investigator decision, 3 subjects withdrew consent for unkown reasons and 2 subjects withdrew based on insurance coverage considerations
Participants by arm
| Arm | Count |
|---|---|
| Convergent Procedure Procedure/Surgery: Convergent Procedure using EPi-Sense-AF Guided Coagulation System with Endocardial Catheter Ablation Treatment
AtriCure EPi-Sense-AF Guided Coagulation System with VisiTrax: Convergent Epicardial Endocardial Ablation Procedure
Endocardial RF Catheter ablation using Open Irrigated-tip RF Abaltion Catheter with unidirectional or bidirectional steering: Endocardial Catheter Ablation Procedure | 102 |
| Standalone Endocardial Catheter Ablation Procedure/Surgery: Endocardial Catheter Ablation Treatment
Endocardial RF Catheter ablation using Open Irrigated-tip RF Abaltion Catheter with unidirectional or bidirectional steering: Endocardial Catheter Ablation Procedure | 51 |
| Total | 153 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Enrollment Closed | 8 | 1 |
| Overall Study | Insurance Coverage | 1 | 0 |
| Overall Study | Intra-operative Exclusion | 2 | 0 |
| Overall Study | Physician Decision | 4 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Convergent Procedure | Standalone Endocardial Catheter Ablation | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 56 Participants | 28 Participants | 84 Participants |
| Age, Categorical Between 18 and 65 years | 46 Participants | 23 Participants | 69 Participants |
| BMI | 32.99 Kg/M2 STANDARD_DEVIATION 5.861 | 35.11 Kg/M2 STANDARD_DEVIATION 7.128 | 33.70 Kg/M2 STANDARD_DEVIATION 6.37 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 100 Participants | 50 Participants | 150 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 177.7 cm STANDARD_DEVIATION 8.43 | 173.9 cm STANDARD_DEVIATION 11.64 | 176.5 cm STANDARD_DEVIATION 9.76 |
| Persistent AF Long-Standing Persistent AF | 38 Participants | 27 Participants | 65 Participants |
| Persistent AF Persistent AF | 64 Participants | 24 Participants | 88 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 96 Participants | 50 Participants | 146 Participants |
| Sex: Female, Male Female | 80 Participants | 27 Participants | 107 Participants |
| Sex: Female, Male Male | 22 Participants | 24 Participants | 46 Participants |
| Smoking History Current Smoker | 9 Participants | 2 Participants | 11 Participants |
| Smoking History Never Smoked | 45 Participants | 28 Participants | 73 Participants |
| Smoking History Past Smoker | 48 Participants | 20 Participants | 68 Participants |
| Smoking History Unknown | 0 Participants | 1 Participants | 1 Participants |
| Weight | 104.3 Kilograms STANDARD_DEVIATION 19.985 | 106.25 Kilograms STANDARD_DEVIATION 23.903 | 105.0 Kilograms STANDARD_DEVIATION 21.31 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 102 | 0 / 51 |
| other Total, other adverse events | 9 / 102 | 0 / 51 |
| serious Total, serious adverse events | 97 / 102 | 41 / 51 |
Outcome results
Primary
Primary Efficacy Endpoint - Number of Participants to Achieve Freedom From AF/AT/AFL.
This binary primary endpoint measures number of patients to achieve freedom from AF/AT/AFL absent class I and III AADs except for previously failed or intolerant I or III AAD with no increase in dosage following the 3-month blanking period through the 12 months post procedure follow-up visit will be compared between the two treatment groups using a chi-square test using a two-sided alpha of .05 to determine if superiority of the treatment arm is attained.
Time frame: 12 Months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Convergent Procedure | Primary Efficacy Endpoint - Number of Participants to Achieve Freedom From AF/AT/AFL. | 67 Participants |
| Standalone Endocardial Catheter Ablation | Primary Efficacy Endpoint - Number of Participants to Achieve Freedom From AF/AT/AFL. | 25 Participants |
p-value: 0.047295% CI: [0.1, 33.2]Chi-square test
Primary
Primary Safety Analysis
The primary safety analysis will measure the number of Major Adverse Events (MAE) collected from the start of the coagulation procedure to 30 days post procedure.
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Convergent Procedure | Primary Safety Analysis | 8 Number of events |
| Standalone Endocardial Catheter Ablation | Primary Safety Analysis | 0 Number of events |
Secondary
AF Freedom Through 12 Months- Absent of an Increased Dose or New Class I/III AAD's.
Number of patients with AF Freedom through 12 Months (ITT Population) absent of an increased dose or new class I/III AAD's
Time frame: 12 Months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Convergent Procedure | AF Freedom Through 12 Months- Absent of an Increased Dose or New Class I/III AAD's. | 71 percentage of participants |
| Standalone Endocardial Catheter Ablation | AF Freedom Through 12 Months- Absent of an Increased Dose or New Class I/III AAD's. | 51 percentage of participants |
Secondary
Change in 6-Minute Walk Score
6 minute walk score was measured by change from baseline compared to 12-months post-procedure between the EPi-Sense and Catheter Ablation groups.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Convergent Procedure | Change in 6-Minute Walk Score | 9.2 Meters | Standard Deviation 120.59 |
| Standalone Endocardial Catheter Ablation | Change in 6-Minute Walk Score | -12.4 Meters | Standard Deviation 190.09 |
Secondary
Change in Atrial Fibrillation Severity Scale (AFSS)
Change was calculated as the value at 12 months minus the value at baseline. The University of Toronto's Atrial Fibrillation Severity Scale (AFSS) is a composite score of overall subject-perceived severity, global well-being, atrial fibrillation frequency, and atrial fibrillation duration. The score ranges from 3 to 30, with higher scores indicating greater atrial fibrillation burden.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Convergent Procedure | Change in Atrial Fibrillation Severity Scale (AFSS) | -11.7 score on a scale | Standard Deviation 7.71 |
| Standalone Endocardial Catheter Ablation | Change in Atrial Fibrillation Severity Scale (AFSS) | -10.3 score on a scale | Standard Deviation 7.16 |
Secondary
Change in Left Atrial Diameter
Change in Left Atrial Diameter at 6 months from baseline.
Time frame: 6 Months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Convergent Procedure | Change in Left Atrial Diameter | 0.1 cm | Standard Deviation 0.62 |
| Standalone Endocardial Catheter Ablation | Change in Left Atrial Diameter | 1.9 cm | Standard Deviation 6.68 |
Secondary
Change in Quality of Life Physical Health Composite Scores Using Short Form Health Survey (SF-36)
Change was calculated as the value at 12 months minus the value at baseline. The 36-Item Short Form Health Survey (SF-36) is used to determine a physical composite score based on following subscales: limitations in physical activities because of health problems; limitations in usual role activities because of physical health problems; bodily pain; vitality (energy and fatigue); and general health perceptions. The subscale scores are transformed into a range from 0 to 100, with 0=worst HRQL, 100=best HRQL. The physical component scores are constructed as a T-score with a mean of 50 and standard deviation of 10 and no minimum or maximum score, with higher scores indicating better health status.
Time frame: 12 Months
Population: Subjects evaluated for quality of life using SF- 36 survey.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Convergent Procedure | Change in Quality of Life Physical Health Composite Scores Using Short Form Health Survey (SF-36) | 7.3 score on a scale | Standard Deviation 10.67 |
| Standalone Endocardial Catheter Ablation | Change in Quality of Life Physical Health Composite Scores Using Short Form Health Survey (SF-36) | 5.7 score on a scale | Standard Deviation 10.49 |
Secondary
Number of Patients With AF Burden Reduction of at Least 90% at 12 Months Compared to Baseline
AF Burden Reduction of at Least 90% at 12-Months (ITT Population): The first secondary effectiveness endpoint in the fixed-sequence testing was defined as at least 90% reduction in AF burden, absent of an increased dose or new class I/III AADs, at 12 months compared to baseline.
Time frame: 12 Months
Population: The number of subjects in the EPi- Sense group that achieved at least 90% reduction at 12 months, compared to subjects in the Catheter Ablation group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Convergent Procedure | Number of Patients With AF Burden Reduction of at Least 90% at 12 Months Compared to Baseline | 60 Participants |
| Standalone Endocardial Catheter Ablation | Number of Patients With AF Burden Reduction of at Least 90% at 12 Months Compared to Baseline | 25 Participants |
Secondary
Number of Subjects With AF Burden Reduction of at Least 90% at 12 Months Relative to Baseline, Regardless of Class I/III AADs.
Number of subjects with AF freedom through 12 months achieved in the EPi-Sense group compared to subjects in the Catheter Ablation group.
Time frame: 12 Months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Convergent Procedure | Number of Subjects With AF Burden Reduction of at Least 90% at 12 Months Relative to Baseline, Regardless of Class I/III AADs. | 95 percentage of participants |
| Standalone Endocardial Catheter Ablation | Number of Subjects With AF Burden Reduction of at Least 90% at 12 Months Relative to Baseline, Regardless of Class I/III AADs. | 88.6 percentage of participants |
Secondary
Quality of Life-Change in SF-36 Mental Health Composite Score Using Short Form Survey (SF-36)
Change was calculated as the value at 12 months minus the value at baseline. The 36-Item Short Form Health Survey (SF-36) is used to determine a mental composite score based on the following subscales: general mental health (psychological distress and well-being); limitations in usual role activities because of emotional problems; and general health perceptions. The subscale scores are transformed into a range from 0 to 100, with 0=worst HRQL, 100=best HRQL. The physical and mental component scores are constructed as a T-score with a mean of 50 and standard deviation of 10 and no minimum or maximum score, with higher scores indicating better health status.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Convergent Procedure | Quality of Life-Change in SF-36 Mental Health Composite Score Using Short Form Survey (SF-36) | 5.7 score on a scale | Standard Deviation 10.51 |
| Standalone Endocardial Catheter Ablation | Quality of Life-Change in SF-36 Mental Health Composite Score Using Short Form Survey (SF-36) | 7.7 score on a scale | Standard Deviation 12.78 |
Secondary
Secondary Safety Endpoint - Serious Adverse Events Through 12 Months Post-procedure.
The secondary safety endpoint for the study was the number of participants with serious adverse events (SAEs) in the study through the 12-months post-procedure.
Time frame: 12 month
Population: Summary of Serious Adverse Events within 12 months occurring in \>3% of the subjects in any treatment group (Safety Population)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Convergent Procedure | Secondary Safety Endpoint - Serious Adverse Events Through 12 Months Post-procedure. | Cardiac Disorders- Pericardial Effusion | 4 Participants |
| Convergent Procedure | Secondary Safety Endpoint - Serious Adverse Events Through 12 Months Post-procedure. | Infections and Infestations- Pneumonia | 3 Participants |
| Convergent Procedure | Secondary Safety Endpoint - Serious Adverse Events Through 12 Months Post-procedure. | Cardiac Disorders- Sinus Node Dysfunction | 0 Participants |
| Convergent Procedure | Secondary Safety Endpoint - Serious Adverse Events Through 12 Months Post-procedure. | Respiratory, Thoracic & Mediastinal Disorder- Pulmonary Edema | 3 Participants |
| Convergent Procedure | Secondary Safety Endpoint - Serious Adverse Events Through 12 Months Post-procedure. | Cardiac Disorders- Pericarditis | 3 Participants |
| Convergent Procedure | Secondary Safety Endpoint - Serious Adverse Events Through 12 Months Post-procedure. | General Disorder and Administration Site-Chest Pain | 3 Participants |
| Convergent Procedure | Secondary Safety Endpoint - Serious Adverse Events Through 12 Months Post-procedure. | Cardiac Disorders-Cardiac Failure Congestive | 5 Participants |
| Convergent Procedure | Secondary Safety Endpoint - Serious Adverse Events Through 12 Months Post-procedure. | Not applicable | 77 Participants |
| Convergent Procedure | Secondary Safety Endpoint - Serious Adverse Events Through 12 Months Post-procedure. | Cardiac Disorders-Cardiac Tamponade | 4 Participants |
| Standalone Endocardial Catheter Ablation | Secondary Safety Endpoint - Serious Adverse Events Through 12 Months Post-procedure. | Not applicable | 44 Participants |
| Standalone Endocardial Catheter Ablation | Secondary Safety Endpoint - Serious Adverse Events Through 12 Months Post-procedure. | Cardiac Disorders-Cardiac Tamponade | 0 Participants |
| Standalone Endocardial Catheter Ablation | Secondary Safety Endpoint - Serious Adverse Events Through 12 Months Post-procedure. | Cardiac Disorders- Pericardial Effusion | 0 Participants |
| Standalone Endocardial Catheter Ablation | Secondary Safety Endpoint - Serious Adverse Events Through 12 Months Post-procedure. | Cardiac Disorders- Pericarditis | 0 Participants |
| Standalone Endocardial Catheter Ablation | Secondary Safety Endpoint - Serious Adverse Events Through 12 Months Post-procedure. | Cardiac Disorders- Sinus Node Dysfunction | 2 Participants |
| Standalone Endocardial Catheter Ablation | Secondary Safety Endpoint - Serious Adverse Events Through 12 Months Post-procedure. | Cardiac Disorders-Cardiac Failure Congestive | 1 Participants |
| Standalone Endocardial Catheter Ablation | Secondary Safety Endpoint - Serious Adverse Events Through 12 Months Post-procedure. | Infections and Infestations- Pneumonia | 4 Participants |
| Standalone Endocardial Catheter Ablation | Secondary Safety Endpoint - Serious Adverse Events Through 12 Months Post-procedure. | Respiratory, Thoracic & Mediastinal Disorder- Pulmonary Edema | 0 Participants |
| Standalone Endocardial Catheter Ablation | Secondary Safety Endpoint - Serious Adverse Events Through 12 Months Post-procedure. | General Disorder and Administration Site-Chest Pain | 0 Participants |