Clinical trial NCT03448562: CPVI Alone Versus. CPVI Plus Electrophysiological Substrate Ablation in the LA During SR for the Treatment of Non-PAF
Official title: Circumferential Pulmonary Vein Isolation Alone Versus. Circumferential Pulmonary Vein Isolation Plus Electrophysiological Substrate Ablation in the Left Atrium During Sinus Rhythm for the Treatment of Non-paroxysmal Atrial Fibrillation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Atrial Fibrillation
Keywords: Atrial Fibrillation
Pulmonary Vein Isolation
Catheter Ablation
Substrate Modification
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
Collaborators: name: First Affiliated Hospital of Zhejiang University
name: Fudan University
name: First Affiliated Hospital of Wannan Medical College
name: The Second Hospital of Hebei Medical University
name: General Hospital of Shenyang Military Region
name: First Affiliated Hospital, Sun Yat-Sen University
name: Guangdong Provincial People's Hospital
name: Zhongda Hospital
name: University of Pennsylvania
name: Southlake Regional Health Centre
name: German Heart Institute
name: Asklepios Kliniken Hamburg GmbH
name: National University Hospital, Singapore
name: Royal Brompton & Harefield NHS Foundation Trust
name: National Heart Centre Singapore
name: Semmelweis University Heart and Vascular Center
name: University of Minnesota
First posted: 2018-02-28
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this investigation is to compare the efficacy of two different AF ablation strategies in patients with non-paroxysmal AF: CPVI plus electrophysiologic substrate ablation in the left atrium during sinus rhythm (STABLE-SR) and CPVI alone.

Detailed description: BACKGROUND: Atrial fibrillation (AF) is the most common cardiac rhythm disorder, which affects patients' morbidity and mortality. AF ablation has emerged as a promising treatment strategy, offering the possibility of a durable treatment. Currently, there is no general agreement regarding NPAF ablation strategy. Obviously, pulmonary vein isolation is the corner stone for all types of AF ablation. The consensus is that CPVI alone is insufficient for NPAF ablation. However, the recent clinical trials did not show the additional benefits of other substrate modification strategies. Furthermore, the widely used cryo-ablation dilutes the concept that NPAF needs additional substrate modification to further improve the clinical outcome. It seems that CPVI only as the optimal strategy is more commonly accepted for NPAF patients in most of the centers. Based on the results from our pilot study and STABLE-SR trial, we believe that fibrotic substrate modification beyond CPVI is very promising for NPAF ablation, but its superiority over CPVI alone needs a large scaled randomized trial to prove.

AIM OF THE STUDY: The primary objective of this investigation is to compare the efficacy of two different AF ablation strategies in patients with non-paroxysmal AF: CPVI plus electrophysiologic substrate ablation in the left atrium during sinus rhythm (STABLE-SR) and CPVI alone. The primary endpoint is freedom from AF and/or ATs with or without antiarrhythmic drugs (AADs) at 12months after a single-ablation procedure. AF and/or AT occurring in the first 3 months after the ablation (blanking period) was censored. Each episode lasts \> 30 seconds. The secondary endpoint are incidence of peri-procedural complications, including stroke, PV stenosis, cardiac perforation, esophageal injury and death; procedure time; fluoroscopy time (including the total fluoroscopy time, during CPVI and after CPVI); the occurrence of the conversion from AF to AT, and its relationship with long-term outcome; the relationship between acute termination of AF and long term outcome.

STUDY DESIGN: This is a randomized, prospective, parallel, single-blind multicenter design. The enrollment target for this investigation is 300 patients. Patients are randomized in a 1:1 fashion into one of the investigation arms: CPVI plus electrophysiologic substrate ablation in the left atrium during sinus rhythm (STABLE-SR) and CPVI alone. Follow-up for these patients includes visits at 3 m, 6 m, 9 m, 12 m.

Eligibility criteria: Inclusion Criteria:

* Patients age is 18-80 years;
* Patients with non-paroxysmal AF; non-paroxysmal AF will be defined as a sustained episode lasting \> 7 days;
* Patients can sign the written informed consent for the study;
* Patients can endure the required follow-up.

Exclusion Criteria:

* Patients with previous radiofrequency ablation;
* Patients with PLT count less than 80×109/L, or with contraindications to systemic anticoagulation with heparin or Coumadin or a direct thrombin inhibitor;
* Patients with left atrial size ≥ 55 mm (2D echocardiography, parasternal long-axis view);
* Patients with thromboemboli in LA (TEE or MSCT);
* Patients with severe structural cardiac disease (medium or severe mitral regurgitation, DCM, HCM, or other severe valvular heart diseases);
* Patients with abnormal thyroid function;
* Patients with severe liver or renal dysfunction (AST or ALT \> 3-fold of upper limit value; the SCr \> 3.5 mg/dl or Ccr \< 30 ml/min);
* Previous surgery history in last 3 months;
* Patients with life expectancy \< 12 months; and
* Patients who are pregnant.

Primary outcomes:
measure: Freedom from AF and/or ATs with or without antiarrhythmic drugs (AADs)
timeFrame: at least 12 months follow up
Secondary outcomes:
measure: Incidence of peri-procedural complications
timeFrame: 1 week after patient enrollment
measure: Procedure time
timeFrame: 1 week after patient enrollment
measure: Fluoroscopy time
timeFrame: 1 week after patient enrollment
measure: Occurrence of the conversion from AF to AT
timeFrame: at least 12 months follow up
measure: Relationship between acute termination of AF and long term outcome
timeFrame: at least 12 months follow up
Other outcomes:
Locations:
city: Nanjing
country: China
facility: The First Affiliated Hospital of Nanjing Medical University
state: Jiangsu
Study officials:
References:
citation: Yang G, Zheng L, Jiang C, Fan J, Liu X, Zhan X, Li J, Wang L, Yang H, Zhu W, Du H, Ma G, Ma W, Kojodjojo P, Chen M; STABLE-SR-II Investigators. Circumferential Pulmonary Vein Isolation Plus Low-Voltage Area Modification in Persistent Atrial Fibrillation: The STABLE-SR-II Trial. JACC Clin Electrophysiol. 2022 Jul;8(7):882-891. doi: 10.1016/j.jacep.2022.03.012. Epub 2022 Apr 27.