Paroxysmal Atrial Fibrillation (PAF)
Conditions
Keywords
Paroxysmal Atrial Fibrillation, Cardiac Arrhythmias, Heart Disease, Cardiovascular Disease, Radiofrequency Ablation
Brief summary
The purpose of this study is to establish the safety and effectiveness of the Blazer Open-Irrigated radiofrequency ablation catheter for the treatment of drug refractory, recurrent, symptomatic, paroxysmal atrial fibrillation.
Detailed description
The ZERO-AF trial is a prospective, multicenter, single blind, 1:1 randomized study. The trial is designed to demonstrate that the safety and effectiveness of the Blazer® Open-Irrigated Ablation Catheter are non-inferior to the safety and effectiveness of the control catheters, for the treatment drug refractory, recurrent, symptomatic, paroxysmal atrial fibrillation. The control catheters are open-irrigated radiofrequency ablation catheters that are approved in the United States for the treatment of drug refractory recurrent symptomatic paroxysmal atrial fibrillation, when used with compatible three-dimensional electroanatomic mapping systems.
Interventions
DEVICEBlazer Open-Irrigated Ablation Catheter (Boston Scientific)
DEVICEFDA Approved Open-Irrigated Ablation Catheter
Sponsors
Boston Scientific Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* History of recurrent symptomatic PAF with ≥2 episodes reported within the 365 days prior to enrollment o PAF is AF episodes that last ≥30 seconds in duration and terminate within 7 days. * At least 1 episode of PAF documented by Holter monitor, rhythm strip, trans-telephonic monitor (TTM), or 12-lead ECG in the 365 days prior to enrollment * Refractory to at least one Beta Blocker, Calcium Channel Blocker, Class I OR Class III anti-arrhythmic drug (AAD) * Age 18 or above, or of legal age to give informed consent specific to state and national law * Competent and willing to provide written informed consent to participate in the study and agree to comply with follow-up visits and evaluation
Exclusion criteria
* Have any of the following heart conditions within 90 days prior to enrollment: * New York Heart Association (NYHA) Class III or IV * Left ventricular ejection fraction (LVEF) \<35% * Left atrial (LA) diameter \>5.5 cm * Unstable angina or ongoing myocardial ischemia * Transmural myocardial infarction (MI) * Congenital structural heart disease that increases the risk of ablation or precludes catheter placement * Undergone any left atrial catheter or surgical ablation * Have had a coronary intervention, cardiac surgery, or other cardiac ablation within 90 days prior to enrollment * Had \>1 AF episode lasting greater than 7 days, with no episodes having lasted greater than 30 days, within the past year * Subjects regularly prescribed amiodarone therapy during the 120 days prior to enrollment * Contraindication to anticoagulation therapy * Creatinine \>2.5mg/dl or creatinine clearance \<30mL/min within 90 days (3 months) prior to enrollment * Prosthetic mitral or tricuspid heart valves * Confirmed cardiac thrombus within 30 days (1 month) prior to enrollment * Implanted pacemaker, ICD, or CRT leads within 180 days (6 months) prior to enrollment * History of CVA, TIA or PE within 180 days (6 months) prior to enrollment * Left atrial appendage closure device * Any other significant uncontrolled or unstable medical condition (e.g. sepsis, acute metabolic illness, end stage COPD) * Enrolled in any concurrent clinical trial without documented pre-approval from BSC * Women who are pregnant or plan to become pregnant within the course of their participation in the investigation * Life expectancy ≤ 2 years (730 days) per physician opinion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Procedure-related Complication Free Rate | 12 Months | The safety of the Blazer OI catheter will be evaluated by demonstrating that the investigational group serious adverse event rate is non-inferior to that of the control group. The safety of the Blazer OI catheter will be evaluated by demonstrating that the investigational group rate of significant pulmonary vein stenosis (≥70% reduction in diameter from baseline) and atrio-esophageal fistulas is non-inferior to that of the control group. |
| Chronic Success Rate | Within 12 months of the index procedure | The primary effectiveness of the Blazer OI catheter will be evaluated by demonstrating that the proportion of subjects free from failure\* in the investigational group is non-inferior to those in the control group. \*failure is defined as a randomized subject being an acute procedural failure, having more than one repeat procedure during the 90 day blanking period or having a documented symptomatic atrial fibrillation, atrial tachycardia, atrial fibrillation between 91 days and 12 months post-procedure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Acute Success | Acute- During Index Procedure, 20 minutes after confirmation of Pulmonary Vein Isolation | Demonstration that the investigational group acute procedural success rate is non-inferior to that of the control group. Acute procedural success is defined as a subject that successfully had all clinically relevant veins electrically isolated, by demonstration of entrance block at a minimum and no evidence of exit conduction with the randomized investigational or control catheter only. |
Countries
Australia, Czechia, France, Germany, Portugal, Spain, Sweden, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Blazer Open-Irrigated Ablation Catheter Blazer Open-Irrigated Ablation Catheter and Ablation Catheter Cable used in conjunction with a compatible electroanatomic mapping system
Blazer Open-Irrigated Ablation Catheter (Boston Scientific) | 167 |
| Control FDA approved Open-Irrigated Radiofrequency Ablation Catheter system and compatible electroanatomic mapping system for the treatment of paroxysmal atrial fibrillation.
FDA Approved Open-Irrigated Ablation Catheter | 172 |
| Blazer Open-Irrigated Ablation Catheter Roll-In Blazer Open-Irrigated Ablation Catheter Roll-In Subjects (Not randomized) | 56 |
| Control Roll-In Non-Randomized Subjects treated with an FDA approved Open-Irrigated Radiofrequency Ablation Catheter system and compatible electroanatomic mapping system for the treatment of paroxysmal atrial fibrillation.
FDA Approved Open-Irrigated Ablation Catheter | 3 |
| Total | 398 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 | 0 | 0 |
| Overall Study | Attempt subject | 2 | 3 | 2 | 0 |
| Overall Study | Death | 1 | 1 | 0 | 0 |
| Overall Study | Did not meet eligibility criteria | 4 | 6 | 1 | 1 |
| Overall Study | Equipment/Device Availability | 0 | 1 | 0 | 0 |
| Overall Study | Insurance | 0 | 0 | 1 | 1 |
| Overall Study | Lost to Follow-up | 2 | 5 | 1 | 0 |
| Overall Study | Patient unable to be compliant | 1 | 0 | 0 | 0 |
| Overall Study | Physician choice to use different device | 1 | 2 | 4 | 0 |
| Overall Study | Physician Decision | 3 | 2 | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 1 | 1 | 0 |
| Overall Study | Subject moved out of state | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 11 | 4 | 3 | 0 |
Baseline characteristics
| Characteristic | Control | Blazer Open-Irrigated Ablation Catheter Roll-In | Control Roll-In | Total | Blazer Open-Irrigated Ablation Catheter |
|---|---|---|---|---|---|
| Age, Continuous | 59 years STANDARD_DEVIATION 10 | 62 years STANDARD_DEVIATION 10 | 61 years STANDARD_DEVIATION 10 | 60 years STANDARD_DEVIATION 11 | 60 years STANDARD_DEVIATION 11 |
| Height | 174 cm STANDARD_DEVIATION 9 | 175 cm STANDARD_DEVIATION 11 | 175 cm STANDARD_DEVIATION 11 | 174 cm STANDARD_DEVIATION 10 | 173 cm STANDARD_DEVIATION 9 |
| New York Heart Assessment (NYHA) Class I | 64 Participants | 20 Participants | 3 Participants | 154 Participants | 67 Participants |
| New York Heart Assessment (NYHA) Class II | 13 Participants | 10 Participants | 0 Participants | 40 Participants | 17 Participants |
| New York Heart Assessment (NYHA) Class Non Heart Failure (HF) | 92 Participants | 24 Participants | 0 Participants | 192 Participants | 76 Participants |
| New York Heart Assessment (NYHA) Class Not Assessed | 3 Participants | 2 Participants | 0 Participants | 12 Participants | 7 Participants |
| Region of Enrollment Australia | 5 Participants | 2 Participants | 0 Participants | 13 Participants | 6 Participants |
| Region of Enrollment France | 3 Participants | 0 Participants | 0 Participants | 6 Participants | 3 Participants |
| Region of Enrollment Germany | 18 Participants | 0 Participants | 0 Participants | 36 Participants | 18 Participants |
| Region of Enrollment Portugal | 2 Participants | 3 Participants | 1 Participants | 9 Participants | 3 Participants |
| Region of Enrollment Spain | 28 Participants | 4 Participants | 0 Participants | 59 Participants | 27 Participants |
| Region of Enrollment Sweden | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Region of Enrollment United Kingdom | 3 Participants | 1 Participants | 0 Participants | 7 Participants | 3 Participants |
| Region of Enrollment United States | 112 Participants | 46 Participants | 2 Participants | 267 Participants | 107 Participants |
| Resting Heart Rate | 67 bpm STANDARD_DEVIATION 15 | 68 bpm STANDARD_DEVIATION 17 | 68 bpm STANDARD_DEVIATION 7 | 69 bpm STANDARD_DEVIATION 17 | 71 bpm STANDARD_DEVIATION 19 |
| Sex: Female, Male Female | 65 Participants | 15 Participants | 1 Participants | 143 Participants | 62 Participants |
| Sex: Female, Male Male | 107 Participants | 41 Participants | 2 Participants | 255 Participants | 105 Participants |
| Weight | 90 kg STANDARD_DEVIATION 22 | 94 kg STANDARD_DEVIATION 21 | 79 kg STANDARD_DEVIATION 15 | 90 kg STANDARD_DEVIATION 21 | 89 kg STANDARD_DEVIATION 19 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 159 | 1 / 167 | 0 / 51 | 0 / 1 |
| other Total, other adverse events | 104 / 159 | 95 / 167 | 33 / 51 | 0 / 1 |
| serious Total, serious adverse events | 66 / 159 | 65 / 167 | 19 / 51 | 0 / 1 |
Outcome results
Primary
Chronic Success Rate
The primary effectiveness of the Blazer OI catheter will be evaluated by demonstrating that the proportion of subjects free from failure\* in the investigational group is non-inferior to those in the control group. \*failure is defined as a randomized subject being an acute procedural failure, having more than one repeat procedure during the 90 day blanking period or having a documented symptomatic atrial fibrillation, atrial tachycardia, atrial fibrillation between 91 days and 12 months post-procedure.
Time frame: Within 12 months of the index procedure
Population: Outcome Measures were not assessed for the non-randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Blazer Open-Irrigated Ablation Catheter | Chronic Success Rate | 102 Participants |
| Control | Chronic Success Rate | 108 Participants |
Primary
Procedure-related Complication Free Rate
The safety of the Blazer OI catheter will be evaluated by demonstrating that the investigational group serious adverse event rate is non-inferior to that of the control group. The safety of the Blazer OI catheter will be evaluated by demonstrating that the investigational group rate of significant pulmonary vein stenosis (≥70% reduction in diameter from baseline) and atrio-esophageal fistulas is non-inferior to that of the control group.
Time frame: 12 Months
Population: Outcome Measures were not assessed for the non-randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Blazer Open-Irrigated Ablation Catheter | Procedure-related Complication Free Rate | 140 Participants |
| Control | Procedure-related Complication Free Rate | 148 Participants |
Secondary
Acute Success
Demonstration that the investigational group acute procedural success rate is non-inferior to that of the control group. Acute procedural success is defined as a subject that successfully had all clinically relevant veins electrically isolated, by demonstration of entrance block at a minimum and no evidence of exit conduction with the randomized investigational or control catheter only.
Time frame: Acute- During Index Procedure, 20 minutes after confirmation of Pulmonary Vein Isolation
Population: Outcome Measures were not assessed for the non-randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Blazer Open-Irrigated Ablation Catheter | Acute Success | 155 Participants |
| Control | Acute Success | 163 Participants |