A Global Randomized Trial Comparing Pulsed Field Ablation of Pulmonary Veins Plus Extra-PV Sources Utilizing Electrographic Flow Mapping Versus Pulmonary Veins Plus Posterior Wall in Persistent Atrial Fibrillation Patients.
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 699
- 试验地点
- 73
- 主要终点
- Primary Safety Endpoint
研究概览
简要总结
The purpose of this study is to establish the safety of the pulsed field ablation (PFA) therapy of Pulmonary Veins and Electrographic Flow (EGF) identified extra-PV sources of atrial fibrillation (PVI + EGF ablation of sources) and to demonstrate its non-inferiority in effectiveness compared to PFA of Pulmonary Veins and LA Posterior Wall (PVI+ PWA) in the treatment of de novo symptomatic drug-refractory persistent atrial fibrillation (PersAF).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
The investigators and staffs will be blinded to the EGF maps in Control Arm.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥ 18 years of age, or older if required by local law
- •Have symptomatic drug-refractory1, persistent AF2, confirmed by both:
- •Documentation, such as physician note, of persistent continuous AF for > 7 days and ≤ 365 days and the arrhythmia symptoms
- •Documentation, within 180 days of enrollment date of either:
- •A 24-hour continuous ECG recording confirming continuous AF or
- •Two (2) ECGs (from any regulatory cleared rhythm monitoring device) showing continuous AF taken at least 7 days apart
- •Willing and capable of providing informed consent
- •Willing and capable of participating in all follow-up assessments and testing associated with this clinical investigation at an approved clinical investigational center
- •Willing to receive LUX-Dx™ insertable cardiac monitor (ICM) during the study or already has a LUX-Dx™ ICM that was inserted ≤ 6 months (i.e., within 180 days) of consent, and willing to comply to the LUX-Dx Latitude Clarity transmission instructions
排除标准
- •Any of the following atrial conditions:
- •Left atrial anteroposterior diameter ≥ 5.5 cm, or if1 LA diameter not available, non-indexed volume >100 ml (physician note or imaging)
- •Any prior left atrial ablation
- •Any prior atrial surgery
- •Current atrial myxoma
- •Current left atrial thrombus
- •Any PV abnormality, stenosis, or stenting (common and middle PVs are admissible)
- •Any of the following cardiovascular conditions:
- •History of sustained ventricular tachycardia or any ventricular fibrillation
- •Severe right ventricular dysfunction with documented echocardiography and/or hemodynamic data, per Investigator's discretion
- •AF that is secondary to electrolyte imbalance, thyroid disease, alcohol, or other reversible / non-cardiac causes
- •Cardiac devices and implants:
- •Current or anticipated pacemaker, implantable cardioverter defibrillator or cardiac resynchronization therapy devices
- •Implantable loop recorder, other than LUX-Dx
- •Interatrial baffle, patent foramen ovale or atrial septal defect closure device or patch
- •Any left atrial appendage closure or occlusion device
- •Presence of any of the following valvular conditions:
- •Any prosthetic heart valve, stenotic valves, ring or repair
- •Moderate to severe mitral valve stenosis
- •More than moderate mitral regurgitation
- •Hypertrophic or amyloid cardiomyopathy
- •Any IVC filter, known inability to obtain vascular access or other contraindication to femoral access
- •Awaiting cardiac transplantation or other planned cardiac surgery within the next 12 months
- •Severe right ventricular dysfunction with documented echocardiography and/or hemodynamic data.
- •Any of the following conditions at Baseline:
- •Heart failure associated with NYHA Class III or IV
- •Most recent documented LVEF < 40% within the previous 12 months
- •Body Mass Index (BMI) > 45.0
- •Known coagulopathy or bleeding disorder
- •Contraindication to, or unwillingness to use systemic anticoagulation, or acceptable alternatives, pre-, intra- and post-procedure to achieve adequate anticoagulation
- •Women who are confirmed to be pregnant or lactating at the time of the ablation procedure
- •Severe lung disease, severe pulmonary hypertension, or any lung disease involving abnormal blood gases or requiring supplemental oxygen
- •Active malignancy (other than squamous cell carcinoma)
- •Clinically significant gastrointestinal problems involving the esophagus or stomach including severe or erosive esophagitis, uncontrolled gastric reflux, gastroparesis, esophageal candidiasis or active gastroduodenal ulceration
- •Known active systemic infection
- •Untreated diagnosed obstructive sleep apnea with apnea hypopnea index classification of severe (>30 pauses per hour) as per the guidelines
- •Predicted life expectancy less than one year per investigator medical judgement
- •Subjects who are currently enrolled in another investigational study or registry that would directly interfere with the current study, except when the subject is participating in a mandatory governmental registry, or a purely observational registry with no associated treatments; each instance must be brought to the attention of the Sponsor to determine eligibility
- •Required use of phosphodiesterase inhibitors within 24 hours of the ablation procedure
- •Uncontrolled hypertension (SBP > 160 mmHg or DBP > 95 mmHg on two (2) BP measurements at baseline assessment not attributable to white coat syndrome per Investigator opinion
- •CHA2DS2-VASc score ≥ 5
- •Known allergic drug reaction to nitroglycerin (excluding hypotension)
- •Unwillingness to receive, or unable to tolerate, a subcutaneous, chronically inserted LUX-Dx ICM device
- •Any of the following congenital conditions:
- •Congenital heart disease with any clinically significant residual anatomic or conduction abnormality
- •History of known congenital methemoglobinemia
- •History of known G6PD deficiency
- •Any of the following conditions in the medical history:
- •Solid organ or hematologic transplant, or currently being evaluated for a transplant
- •Any prior history or current evidence of hemi-diaphragmatic paralysis or paresis
- 另有 13 项未显示
研究组 & 干预措施
Control Arm
PVI + PWA: The Control Arm, consisting of subjects undergoing PVI + PWA. PWA will be performed adjunctive to PVI per protocol Section 10.8.10. Following confirmation of PWA, EGF mapping will be performed in the LA and RA, while Investigators, lab/nursing staff, and research personnel are blinded to the EGF maps.
干预措施: OptiMap System (non-ablative) (Device)
Treatment Arm
PVI + EGF source(s) ablation: The Treatment Arm, consisting of subjects undergoing PVI + EGF source(s) ablation. Adjunctive to PVI, the EGF-identified active sources above threshold will be ablated per protocol Section 10.8.11. If following PVI, a narrow channel that is approximately ≤ 1 cm is identified in the LAPW, ablation may be performed using the FARAPOINT Catheter.
干预措施: FARAPOINT Pulsed Field Ablation System (Device)
Treatment Arm
PVI + EGF source(s) ablation: The Treatment Arm, consisting of subjects undergoing PVI + EGF source(s) ablation. Adjunctive to PVI, the EGF-identified active sources above threshold will be ablated per protocol Section 10.8.11. If following PVI, a narrow channel that is approximately ≤ 1 cm is identified in the LAPW, ablation may be performed using the FARAPOINT Catheter.
干预措施: FARAPULSE Pulsed Field Ablation (PFA) System and Opal HDx Mapping System (Device)
Control Arm
PVI + PWA: The Control Arm, consisting of subjects undergoing PVI + PWA. PWA will be performed adjunctive to PVI per protocol Section 10.8.10. Following confirmation of PWA, EGF mapping will be performed in the LA and RA, while Investigators, lab/nursing staff, and research personnel are blinded to the EGF maps.
干预措施: FARAPULSE Pulsed Field Ablation (PFA) System and Opal HDx Mapping System (Device)
Treatment Arm
PVI + EGF source(s) ablation: The Treatment Arm, consisting of subjects undergoing PVI + EGF source(s) ablation. Adjunctive to PVI, the EGF-identified active sources above threshold will be ablated per protocol Section 10.8.11. If following PVI, a narrow channel that is approximately ≤ 1 cm is identified in the LAPW, ablation may be performed using the FARAPOINT Catheter.
干预措施: OptiMap System (non-ablative) (Device)
结局指标
主要结局
Primary Safety Endpoint
时间窗: 60 Days
The primary safety endpoint is the rate of ITT subjects in the PVI+EGF arm with one or more of the following serious device- or procedure-related Composite Adverse Events (CAEs) assessed through 60 days following the Index Procedure.
Primary Effectiveness Endpoint
时间窗: 365 Days
The primary effectiveness endpoint is the rate of ITT subjects with treatment success in the PVI+EGF arm vs. the PVI+PWA control arm through Day 365, aiming to demonstrate non-inferiority of PVI+EGF compared to the PVI+PWA control.
Primary Safety Endpoint
时间窗: 60 Days
The primary safety endpoint is the rate of ITT subjects in the PVI+EGF arm with one or more of the following serious device- or procedure-related Composite Adverse Events (CAEs) assessed through 60 days following the Index Procedure.
Primary Effectiveness Endpoint
时间窗: 365 Days
The primary effectiveness endpoint is the rate of ITT subjects with treatment success in the PVI+EGF arm vs. the PVI+PWA control arm through Day 365, aiming to demonstrate non-inferiority of PVI+EGF compared to the PVI+PWA control.
次要结局
- Secondary Effectiveness Endpoint(365 Days)
- Secondary Effectiveness Endpoint(365 Days)