CPVI With Modified Linear Ablation Versus CPVI in Patients With Long-standing Persistent Atrial Fibrillation (SINUS)

Not Applicable

Recruiting

• Conditions: Long-standing Persistent Atrial Fibrillation; Ablation
• Interventions: Procedure: CPVI-MLA; Procedure: CPVI only

• Registration Number: NCT06516822
• Lead Sponsor: The First Affiliated Hospital with Nanjing Medical University

Brief Summary

Catheter ablation has become as the first-line treatment for patients with symptomatic atrial fibrillation (AF). As the cornerstone of catheter ablation for AF, the safety and efficacy of circumferential pulmonary vein isolation (CPVI) have been confirmed. However, for persistent AF, especially for long-standing persistent AF (LSPAF), the recurrence rate is still high. Whether the ethanol infusion (EI) into the vein of Marshall (EI-VOM) and linear ablation could improve the success rate remains controversial.

The SINUS study is a prospective, multicenter, randomized trial, which is designed to compare the efficacy and safety between CPVI with modified linear ablation (CPVI-MLA) and CPVI only for the treatment of LSPAF.

Detailed Description

The SINUS study will include 320 patients with LSPAF undergoing catheter ablation for the first time. All patients will be randomized to either the CPVI-MLA group or CPVI only group in a 1:1 ratio. The CPVI-MLA strategy is a fixed ablation approach consisting of EI-VOM, CPVI, left atrial posterior wall isolation (PWI), linear ablation of mitral isthmus (MI), left atrial intima adjoining CS (LAI-CS) and cavo-tricuspid isthmus (CTI), and superior vena cava isolation (SVCI). The follow-up is for a minimum of 12 months with rhythm monitoring. The primary endpoint is freedom from any documented atrial arrhythmia including atrial fibrillation (AF), atrial tachycardia (AT), or atrial flutter (AFL) \> 30 seconds after the initial 3 months blanking period without the use of antiarrhythmic drugs (AADs), at 12 months after the index ablation procedure.

Study Timeline

• Study First Submitted: 2024-07-17
• Study First Submitted QC: 2024-07-23
• Study First Posted: 2024-07-24
• Study Start: 2024-07-31
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-06
• Last Update Posted: 2024-11-08
• Primary Completion: 2027-12
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 320

Inclusion Criteria

1. 1. Patients with symptomatic LSPAF refractory to at least one antiarrhythmic drug; LSPAF will be defined as a sustained AF episode lasting ≥ 1 year;
2. AF duration 1-3 years;
3. Age 18 - 75 years;
4. Left atrial diameter (LAD) 43-55 mm on long axis parasternal view;
5. AF recorded within 3 years of enrollment;
6. Patient willing and able to comply with protocol and sign informed consent

Exclusion Criteria

1. Paroxysmal atrial fibrillation;
2. Persistent AF lasting < 1 year or >3 years;
3. Left atrial thrombosis;
4. Patients with a history of catheter ablation for AF;
5. Patients with severe structural heart disease (severe valvular heart disease, hypertrophic cardiomyopathy, dilated cardiomyopathy, etc.);
6. LAD > 55mm on long axis parasternal view;
7. Left ventricular ejection fraction (LVEF) < 40%;
8. Patients with contraindications to low molecular weight heparin, warfarin or novel oral anticoagulants;
9. One-stop procedure for AF ablation and left atrial appendage occlusion;
10. Alcohol allergy or contrast agent allergy;
11. Patients taking cephalosporin antibiotics within 72 hours prior to ablation;
12. Pulmonary artery systolic pressure > 50mmHg;
13. Patients with unstable angina pectoris;
14. Patients who had undergone percutaneous coronary intervention (PCI) within 3 months;
15. Patients who had undergone surgery within 6 months;
16. Patients ready to receive heart transplantation;
17. Patients with a history of thromboembolism within 6 months;
18. Patients with diagnosed atrial myxoma;
19. Patients with severe respiratory diseases;
20. Patients with infectious diseases in active phase;
21. Patients with poorly controlled systemic immune diseases;
22. Patients with uncured malignant hematological diseases;
23. Patients with uncured malignant solid tumors;
24. Patients with untreated hypothyroidism or hyperthyroidism;
25. Patients with severe liver dysfunction (elevation of transaminases [ALT or AST] >3 times the upper limit of normal range);
26. Patients with end-stage renal failure requiring dialysis;
27. Patients with other serious arrhythmias, such as ventricular tachycardia with hemodynamic instability;
28. Pregnant and lactating women;
29. Patients with psychiatric ailments;
30. BMI < 18.5 or ≥ 30kg/m2;
31. Life expectancy < 2 years;
32. Patients unwilling or unable to give informed consent;
33. Patients unwilling or unable to cooperate to complete follow-up.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CPVI-MLA	CPVI-MLA	Patients randomized to the CPVI-MLA group first undergo ethanol infusion in the vein of Marshall (EI-VOM) followed by CPVI, left atrial posterior wall isolation (PWI), linear ablation of mitral isthmus (MI), left atrial intima adjoining CS (LAI-CS) and cavo-tricuspid isthmus (CTI), and superior vena cava isolation (SVCI).
CPVI only	CPVI only	Patients randomized to the CPVI group undergo right PV ablation, followed by the left PV ablation. Radiofrequency ablation should be applied at least 1-2 cm outside of the PV ostia in a wide-area circumferential pattern. Complete CPVI is achieved when all PV potentials within each antrum recorded by the high-density mapping catheter are abolished.

Primary Outcome Measures

Name	Time	Method
Freedom from any documented atrial arrhythmia off AADs	12 months	Freedom from any documented atrial arrhythmia including atrial fibrillation (AF), atrial tachycardia (AT), or atrial flutter (AFL) \> 30 seconds assessed by ECG and Holter after the initial 3 months blanking period without the use of antiarrhythmic drugs (AADs), after the index ablation procedure

Secondary Outcome Measures

Name	Time	Method
Freedom from AFL/AT after multiple procedures	12 months	Freedom from any documented AFL/AT \> 30 seconds assessed by ECG and Holter after the initial 3 month blanking period, after more than one ablation procedure on/off AADs.
AFEQT score change between baseline and 12-month	12 months	Quality of life assessed by AF effect on quality-of-life (AFEQT) questionnaire
Freedom from any documented atrial arrhythmia on/off AADs	12 months	Freedom from any documented atrial arrhythmia \> 30 seconds assessed by ECG and Holter after the initial 3 month blanking period, after the index ablation procedure on/off AADs.
Freedom from any documented AF on/off AADs	12 months	Freedom from any documented AF episodes \> 30 seconds assessed by ECG and Holter after the initial 3 month blanking period, after the index ablation procedure on/off AADs.
AF burden	12 months	AF burden (% time) on continuous monitoring during 12 months after the 3-months blanking period.
Freedom from any documented AFL/AT on/off AADs in patients with successful EI-VOM	12 months	Freedom from any documented AFL/AT episodes \> 30 seconds assessed by ECG and Holter after the initial 3 month blanking period, after the index ablation procedure on/off AADs in patients with successful EI-VOM.
AF burden in patients with successful EI-VOM	12 months	AF burden (% time) on continuous monitoring during 12 months after the 3-months blanking period in patients with successful EI-VOM
AF burden after multiple procedures	12 months	AF burden (% time) on continuous monitoring during 12 months (after the 3-months blanking period) after multiple procedures
Freedom from any documented AFL/AT on/off AADs	12 months	Freedom from any documented AFL/AT episodes \> 30 seconds assessed by ECG and Holter after the initial 3 month blanking period, after the index ablation procedure on/off AADs.
EQ-5D-5L score change between baseline and 12-month	12 months	Quality of life assessed by EuroQol 5-dimension (EQ-5D-5L) scale
Freedom from AF/AFL/AT after multiple procedures	12 months	Freedom from any documented atrial arrhythmia \> 30 seconds assessed by ECG and Holter after the initial 3 month blanking period, after more than one ablation procedure on/off AADs.
Freedom from AF after multiple procedures	12 months	Freedom from any documented AF \> 30 seconds assessed by ECG and Holter after the initial 3 month blanking period, after more than one ablation procedure on/off AADs.
Hospitalization for cardiovascular disease	12 months	Hospitalization for cardiovascular disease (e.g., atrial arrhythmia, heart failure and coronary heart disease)
Incidence of procedural complications	Within 3 months after the procedure	Cardiac tamponade or perforation, phrenic nerve injury, acute coronary occlusion, death, stroke / thromboembolism related to AF ablation, pulmonary vein stenosis, left atrial oesophageal fistula, and vascular complications requiring intervention (e.g., pseudoaneurysm, arteriovenous fistula).

Trial Locations

Locations (10)

Beijing Anzhen Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China

Peking University third hospital; 🇨🇳 Beijing, Beijing, China

Sun Yat-sen Memorial Hospital, Sun Yat-sen University; 🇨🇳 Guangzhou, Guangdong, China

Shenzhen Hospital, Fuwai Hospital, Chinese Academy of Medical Science; 🇨🇳 Shenzhen, Guangdong, China

Zhengzhou University People's Hospital, Henan Provincial People's Hospital; 🇨🇳 Zhengzhou, Henan, China

The First Affiliated Hospital of Nanjing Medical University; 🇨🇳 Nanjing, Jiangsu, China

The First Affiliated Hospital of Dalian Medical University; 🇨🇳 DaLian, Liaoning, China

The First Affiliated Hospital of Shandong First Medical University; 🇨🇳 JiNan, Shandong, China

Xijing Hospital, Air Force Medical University; 🇨🇳 Xi'an, Shanxi, China

Taizhou First People's Hospital; 🇨🇳 Taizhou, Zhejiang, China