Atrial Fibrillation
Conditions
Keywords
Interventional, Radiofrequency Ablation, Persistent Atrial Fibrillation
Brief summary
This is a prospective, multicenter, non-randomized clinical evaluation utilizing the THERMOCOOL SMARTTOUCH® SF catheter compared to a predetermined performance goal.
Detailed description
The purpose of this study is to demonstrate the safety and effectiveness of the THERMOCOOL SMARTTOUCH® SF catheter in the treatment of drug refractory symptomatic persistent atrial fibrillation (PsAF) following standard electrophysiology mapping and radio frequency (RF) ablation procedures.
Interventions
DEVICETHERMOCOOL SMARTTOUCH® SF catheter
Radiofrequency Ablation
Sponsors
Biosense Webster, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Candidates for this study must meet ALL of the following criteria: 1. Documented symptomatic persistent AF, which is defined as continuous AF sustains beyond 7 days and less than 1 year and is documented by the following:. 1. Physician's note indicating continuous AF ≥ 7 days but no more than 1 year; AND 2. Two electrocardiograms (from any forms of rhythm monitoring) showing continuous AF, with electrocardiogram taken at least 7 days apart OR 3. 24-hour Holter within 90 days of the ablation procedure showing continuous AF 2. Failed at least one antiarrhythmic drug (AAD) (class I or III) as evidenced by recurrent symptomatic AF, or intolerable to the AAD. 3. Age 18 years or older. 4. Signed Patient Informed Consent Form (ICF). 5. Able and willing to comply with all pre-, post-, and follow-up testing and requirements.
Exclusion criteria
Candidates for this study will be EXCLUDED from the study if ANY of the following conditions apply: 1. Continuous AF \> 12 months (1-Year) (Longstanding Persistent AF) 2. Previous surgical or catheter ablation for atrial fibrillation 3. Any cardiac surgery within the past 2 months (60 days) (includes percutaneous coronary intervention (PCI)) 4. Coronary Artery Bypass Graft (CABG) surgery within the past 6 months (180 days) 5. Valvular cardiac surgical/percutaneous procedure (i.e., ventriculotomy, atriotomy, and valve repair or replacement and presence of a prosthetic valve) 6. Any carotid stenting or endarterectomy 7. Documented left atrial (LA) thrombus on imaging 8. LA size \> 50 mm (parasternal long axis view) 9. Left ventricular ejection fraction (LVEF) \< 40% 10. Contraindication to anticoagulation (heparin or warfarin) 11. History of blood clotting or bleeding abnormalities 12. MI within the past 2 months (60 days) 13. Documented thromboembolic event (including Transient Ischemic Attack (TIA) within the past 12 months (365 days) 14. Rheumatic Heart Disease 15. Uncontrolled heart failure or New York Heart Association (NYHA) function class III or IV 16. Severe mitral regurgitation (Regurgitant volume ≥ 60 mL/beat, Regurgitant fraction ≥ 50%, and/or Effective regurgitant orifice area ≥ 0.40cm2) 17. Awaiting cardiac transplantation or other cardiac surgery within the next 12 months (365 days) 18. Unstable angina 19. Acute illness or active systemic infection or sepsis 20. AF secondary to electrolyte imbalance, thyroid disease, or reversible or non-cardiac cause. 21. Diagnosed atrial myxoma. 22. Presence of implanted implantable cardioverter defibrillator (ICD) /cardiac resynchronization therapy defibrillator (CRT-D). 23. Significant pulmonary disease, (e.g., restrictive pulmonary disease, constrictive or chronic obstructive pulmonary disease) or any other disease or malfunction of the lungs or respiratory system that produces chronic symptoms. 24. Gastroesophageal Reflux Disease (GERD; active requiring significant intervention not including over-the-counter (OTC) medication) 25. Significant congenital anomaly or medical problem that in the opinion of the investigator would preclude enrollment in this study. 26. Women who are pregnant (as evidenced by pregnancy test if pre-menopausal) 27. Enrollment in an investigational study evaluating another device, biologic, or drug. 28. Presence of intramural thrombus, tumor or other abnormality that precludes vascular access, or manipulation of the catheter. 29. Presence of any other condition that precludes appropriate vascular access. 30. Life expectancy less than 12 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Safety Endpoint - Percentage of Participants With Any PAE Within 7 Days | 7 days (except as noted in analysis population description) | The primary safety endpoint is the incidence of any early onset (within 7 days of the initial and repeat AF ablation procedure) Primary Adverse Events (AE), which are listed below: * Death * Atrio-esophageal fistula\* * Cardiac Tamponade\*\*+/Perforation+ * Myocardial infarction (MI) * Stroke / Cerebrovascular accident (CVA) †, †† * Thromboembolism * Transient Ischemic Attack * Diaphragmatic paralysis * Pneumothorax * Heart block * PV stenosis\* * Pulmonary edema (Respiratory Insufficiency) * Pericarditis * Major Vascular access complication / bleeding |
| Effectiveness: Freedom From Documented Atrial Fibrillation (AF), Atrial Tachycardia (AT), or Atrial Flutter (AFL) Episodes Through 15-month Follow-up | 15-month follow-up | The primary effectiveness endpoint for this study will be freedom from documented atrial fibrillation (AF), atrial tachycardia (AT), or atrial flutter (AFL) episodes through 15-month follow-up (post 3-Month Medication Adjustment Period followed by a 3-Month Therapy Consolidation period (Day 181-450)) and freedom from the following failure modes: * Acute Procedural Failure * Non-Study Catheter Failure * Repeat Ablation Failure * AAD Failure * Surgical Failure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Early Onset Serious Adverse Event (SAE) | 7 days | Occurrence of Early Onset (within 7 days of initial ablation) Serious Adverse Event |
| Acute Procedural Success | Immediate post-procedure | Acute procedural success is defined as confirmation of entrance block in all pulmonary veins. |
| Late Onset Serious Adverse Event (SAE) | >30 days up to 15 months | Occurrence of Late Onset (\>30 days) Serious Adverse Event |
| Peri-Procedural Serious Adverse Event (SAE) | >7 to 30 days | Peri-Procedural (\>7 to 30 days) Serious Adverse Event |
| 15-Month Single Procedure Success | 15-Month | The 15-month single procedure success is defined as freedom from documented AF/AFL/AT recurrence (episodes \> 30 secs) during the Evaluation Period after a single ablation procedure. Any repeat ablation procedure during the Evaluation Period will be deemed effectiveness failure for this analysis. |
Participant flow
Recruitment details
Total of 367 subjects were proposed in the protocol to be enrolled for this study. The enrollment had been completed and closed after reaching a total of 381 enrolled subjects. The last subject was enrolled on February 6th, 2018.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Group Pulmonary vein isolation (PVI) by RF ablation treatment with the THERMOCOOL SMARTTOUCH® SF catheter in persistent AF population. | 381 |
| Total | 381 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
| Overall Study | Excluded | 33 |
| Overall Study | Lost to Follow-up | 20 |
| Overall Study | Withdrawal by Subject | 33 |
Baseline characteristics
| Characteristic | Treatment Group |
|---|---|
| Age, Continuous | 65.6 Years STANDARD_DEVIATION 8.72 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 357 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 17 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 23 Participants |
| Race (NIH/OMB) White | 349 Participants |
| Sex: Female, Male Female | 110 Participants |
| Sex: Female, Male Male | 271 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 348 |
| other Total, other adverse events | 0 / 348 |
| serious Total, serious adverse events | 85 / 348 |
Outcome results
Primary
Effectiveness: Freedom From Documented Atrial Fibrillation (AF), Atrial Tachycardia (AT), or Atrial Flutter (AFL) Episodes Through 15-month Follow-up
The primary effectiveness endpoint for this study will be freedom from documented atrial fibrillation (AF), atrial tachycardia (AT), or atrial flutter (AFL) episodes through 15-month follow-up (post 3-Month Medication Adjustment Period followed by a 3-Month Therapy Consolidation period (Day 181-450)) and freedom from the following failure modes: * Acute Procedural Failure * Non-Study Catheter Failure * Repeat Ablation Failure * AAD Failure * Surgical Failure
Time frame: 15-month follow-up
Population: The PP population was used as the primary analysis population. Subjects who did not complete the 15-month follow-up were considered missing and were excluded from the primary analysis unless the subjects experienced effectiveness failure prior to exiting the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group | Effectiveness: Freedom From Documented Atrial Fibrillation (AF), Atrial Tachycardia (AT), or Atrial Flutter (AFL) Episodes Through 15-month Follow-up | 59.3 Percentage of Participants |
Primary
Primary Safety Endpoint - Percentage of Participants With Any PAE Within 7 Days
The primary safety endpoint is the incidence of any early onset (within 7 days of the initial and repeat AF ablation procedure) Primary Adverse Events (AE), which are listed below: * Death * Atrio-esophageal fistula\* * Cardiac Tamponade\*\*+/Perforation+ * Myocardial infarction (MI) * Stroke / Cerebrovascular accident (CVA) †, †† * Thromboembolism * Transient Ischemic Attack * Diaphragmatic paralysis * Pneumothorax * Heart block * PV stenosis\* * Pulmonary edema (Respiratory Insufficiency) * Pericarditis * Major Vascular access complication / bleeding
Time frame: 7 days (except as noted in analysis population description)
Population: The safety population was used as the primary analysis population. Subjects with missing 3-month follow-up were excluded from the primary analysis unless the subjects experienced a Primary AE prior to the 3-month visit post-procedure. PV stenosis and AE fistula that occurred \> 1 week and cardiac tamponade/perforation that occurred up to 30 days post ablation were also deemed Primary AEs.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group | Primary Safety Endpoint - Percentage of Participants With Any PAE Within 7 Days | 4.7 Percentage of participants |
Secondary
15-Month Single Procedure Success
The 15-month single procedure success is defined as freedom from documented AF/AFL/AT recurrence (episodes \> 30 secs) during the Evaluation Period after a single ablation procedure. Any repeat ablation procedure during the Evaluation Period will be deemed effectiveness failure for this analysis.
Time frame: 15-Month
Population: Per Protocol Population, n=333, minus 3 acute procedural failures and 36 missing outcomes not included in primary effectiveness endpoint calculation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group | 15-Month Single Procedure Success | 182 Participants |
Secondary
Acute Procedural Success
Acute procedural success is defined as confirmation of entrance block in all pulmonary veins.
Time frame: Immediate post-procedure
Population: Per Protocol Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group | Acute Procedural Success | 330 Participants |
Secondary
Early Onset Serious Adverse Event (SAE)
Occurrence of Early Onset (within 7 days of initial ablation) Serious Adverse Event
Time frame: 7 days
Population: Safety Population (number of subjects with study catheter inserted) was the analysis population for secondary safety endpoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group | Early Onset Serious Adverse Event (SAE) | 33 Participants |
Secondary
Late Onset Serious Adverse Event (SAE)
Occurrence of Late Onset (\>30 days) Serious Adverse Event
Time frame: >30 days up to 15 months
Population: Safety Population (number of subjects with study catheter inserted) and excluding subjects who exited prior to 30 days of follow up in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group | Late Onset Serious Adverse Event (SAE) | 59 Participants |
Secondary
Peri-Procedural Serious Adverse Event (SAE)
Peri-Procedural (\>7 to 30 days) Serious Adverse Event
Time frame: >7 to 30 days
Population: Safety Population (number of subjects with study catheter inserted)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group | Peri-Procedural Serious Adverse Event (SAE) | 6 Participants |