Additional Low Voltage Area Ablation in Older Patients With Paroxysmal Atrial Fibrillation (STABLE-SR-III)

Additional Low Voltage Area Ablation in Older Patients With Paroxysmal Atrial Fibrillation: a Randomized Control Trial of STABLE-SR-III

The primary objective of this investigation is to compare the efficacy of two different AF ablation strategies in older patients with paroxysmal AF: Pulmonary vein isolation alone versus additional low-voltage substrate modification during sinus rhythm

Study Overview

• Status: Completed
• Conditions: Paroxysmal Atrial Fibrillation
• Intervention / Treatment: Procedure: CPVI plus low-voltage substrate modification; Procedure: CPVI alone

Detailed Description

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac rhythm disorder. Catheter ablation to the pulmonary veins isolation (PVI) electrically from the left atrium (LA) has been shown to be an effective treatment for paroxysmal AF (PAF). The consensus is that PVI alone is the main strategy for PAF ablation. Based on the results from our pilot study and STABLE-SR trial, that low-voltage modification beyond CPVI is very promising for persistent AF ablation. Whether the low voltage area modification combined with PVI improves outcomes is unclear in older patients with PAF.

AIM OF THE STUDY: The primary objective of this investigation is to compare the efficacy of two different AF ablation strategies in older patients with PAF: PVI alone versus additional low-voltage substrate modification during sinus rhythm. The primary endpoint is freedom from AF and/or ATs with or without antiarrhythmic drugs (AADs) at 12 months after a single-ablation procedure. AF and/or AT occurring in the first 3 months after the ablation (blanking period) was censored. Each atrial tachyarrhythmia episode lasts > 30 seconds monitored by ECG, 24-Holter or 7 days-Holter was defined as recurrence. The secondary endpoint are incidence of periprocedural 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 scar distribution and the relationship of success rate in older PAF patients.

STUDY DESIGN: This is a randomized, prospective, parallel, single-blind multicenter design. The expected freedom from atrial fibrillation in older patients after one ablation procedure was 75% for PVI. Previous study did not include a group assigned to isolation plus additional low-voltage substrate modification during sinus rhythm, so freedom form AF for this procedure was estimated from the literature at 85%. A log-rank test was used for sample-size calculation. To test whether the isolation plus low-voltage substrate modification was superior to isolation only. Then the 369 patients were needed, with a randomization ratio of 1:1, for the study to have a power of 90% at a two-sided alpha level of 0.05. Assuming a dropout rate of 15%, we need 434 patients. Patients are randomized in a 1:1 fashion into one of the investigation arms: CPVI plus low-voltage substrate modification in the left atrium during SR and CPVI alone. Follow-up for these patients includes visits at 3 m, 6 m, 9 m, 12 m.

• Study Type: Interventional
• Enrollment (Actual): 438
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Nanjing, China
    • The First Affiliated Hospital of Nanjing Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 80 years (OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients age is 65-80 years;
• Patients with paroxysmal AF;
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Study Group; PVI with additional low-voltage substrate modification	Procedure: CPVI plus low-voltage substrate modification; CPVI plus low-voltage substrate modification in the left atrium during SR; Other Names: CPVI plus additional low-voltage substrate modification
ACTIVE_COMPARATOR: Control Group; PVI only	Procedure: CPVI alone; circumferential pulmonary vein isolation

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
Procedure time	time that the patient spend in the procedure room	1 week after patient enrollment
Incidence of peri-procedural complications	stroke, cardiac perforation, and death	1 week after patient enrollment
complications during the follow-up	PV stenosis, esophageal injury	1month to 12 months
Fluoroscopy time	the total fluoroscopy time, during PVI alone or PVI plus low-voltage substrate modification	1 week after patient enrollment

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Collaborators: The Second Hospital of Hebei Medical University; The First Affiliated Hospital of Soochow University; Air Force Military Medical University, China; Zhongda Hospital; The Affiliated Hospital of Xuzhou Medical University; First Affiliated Hospital of Wannan Medical College; Second Affiliated Hospital of Nantong University; The Third Affiliated Hospital of Soochow University; Xuzhou Central Hospital, the Affiliated Xuzhou Hospital of Medical College of Southeast University
• Investigators: Principal Investigator: Minglong Chen, The First Affiliated Hospital with Nanjing Medical University

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 24, 2018
• Primary Completion (ACTUAL): August 3, 2020
• Study Completion (ACTUAL): August 17, 2021

Study Registration Dates

• First Submitted: March 1, 2018
• First Submitted That Met QC Criteria: March 9, 2018
• First Posted (ACTUAL): March 12, 2018

Study Record Updates

• Last Update Posted (ACTUAL): May 4, 2022
• Last Update Submitted That Met QC Criteria: April 28, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: ablation; Paroxysmal Atrial Fibrillation; pulmonary vein isolation; substrate modification
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: 2015-SR-085

Drug and device information, study documents

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