CPVI Alone Versus. CPVI Plus Electrophysiological Substrate Ablation in the LA During SR for the Treatment of Non-PAF (STABLE-SR_II)

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

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.

Study Overview

• Status: Unknown
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Procedure: CPVI; Procedure: STABLE-SR

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.

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Recruiting
      • The First Affiliated Hospital of Nanjing Medical University
      • Contact: Gang Yang, MD; Phone Number: 86-18601406982; Email: yanggang201301@163.com
      • Principal Investigator: Chen minglong, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study Group; CPVI plus electrophysiologic substrate ablation in the left atrium during sinus rhythm (STABLE-SR)	Procedure: CPVI; ablate around the pulmonary vein orifice; Procedure: STABLE-SR; homogenization of the low voltage zones and elimination of the complex electrograms from the transitional zones during sinus rhythm
Active Comparator: Control Group; CPVI alone	Procedure: CPVI; ablate around the pulmonary vein orifice

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Freedom from AF and/or ATs with or without antiarrhythmic drugs (AADs)	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.	at least 12 months follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of peri-procedural complications	stroke, PV stenosis, cardiac perforation, esophageal injury and death	1 week after patient enrollment
Procedure time	time that the patient spend in the procedure room	1 week after patient enrollment
Fluoroscopy time	the total fluoroscopy time, during CPVI and after CPVI	1 week after patient enrollment
Occurrence of the conversion from AF to AT	the occurrence of the conversion from AF to AT, and its relationship with long-term outcome	at least 12 months follow up
Relationship between acute termination of AF and long term outcome	the relationship between acute termination of AF and long term outcome	at least 12 months follow up

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Collaborators: National University Hospital, Singapore; University of Pennsylvania; General Hospital of Shenyang Military Region; Fudan University; The Second Hospital of Hebei Medical University; First Affiliated Hospital, Sun Yat-Sen University; University of Minnesota; Semmelweis University Heart and Vascular Center; First Affiliated Hospital of Zhejiang University; Royal Brompton & Harefield NHS Foundation Trust; Guangdong Provincial People's Hospital; Zhongda Hospital; Asklepios Kliniken Hamburg GmbH; German Heart Institute; National Heart Centre Singapore; First Affiliated Hospital of Wannan Medical College; Southlake Regional Health Centre

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2018
• Primary Completion (Anticipated): September 30, 2020
• Study Completion (Anticipated): September 30, 2020

Study Registration Dates

• First Submitted: December 27, 2017
• First Submitted That Met QC Criteria: February 26, 2018
• First Posted (Actual): February 28, 2018

Study Record Updates

• Last Update Posted (Actual): February 11, 2020
• Last Update Submitted That Met QC Criteria: February 7, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Atrial Fibrillation; Catheter Ablation; Pulmonary Vein Isolation; Substrate Modification
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: 2017-SR-322

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No