Randomized Controlled Trial - Catheter Ablation Combined With Left Atrial Appendage Occlusion Versus Catheter Ablation Combined With Oral Anticoagulation for Elderly Frailty Patients With Atrial Fibrillation: Comparison of Efficacy and Safety
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Incidence of Net Adverse Clinical Events (NACE) at 12 Months
研究概览
简要总结
Atrial fibrillation (AF) is the most common arrhythmia, significantly increasing the risk of stroke, heart failure, hospitalization and death in patients. Studies have shown that standardized anticoagulation can effectively reduce the risk of stroke by 64% and the risk of death by 26% in AF patients. Therefore, both European and American guidelines recommend standardized oral anticoagulation (OAC) as an important treatment strategy for stroke prevention in AF patients. However, the use of OAC may also increase the risk of bleeding in patients. Results from large AF anticoagulation randomized trials show that the annual risk of anticoagulation-related bleeding mortality is 2% to 3%. Therefore, according to the guidelines recommendations, assessing the bleeding risk is necessary in patients with anticoagulant indications.
Percutaneous left atrial appendage occlusion (LAAO) is a device-based therapy that aims to prevent ischemic stroke in patients with AF. For patients with contraindications to long-term anticoagulation therapy, LAAO can be considered as an alternative strategy to oral anticoagulation (Class II B recommendation) to prevent ischemic stroke and thromboembolism. Multiple studies have shown that LAAO is non-inferior to warfarin and novel oral anticoagulants in stroke prevention for non-valvular AF patients. Age is not only a risk factor for stroke but also an important risk factor for bleeding. In the elderly population, especially those with frailty, the risk factors for both stroke and bleeding are often increased. Currently, there is insufficient evidence to support the use of OAC in frail elderly patients with relative anticoagulant contraindications. Therefore, elderly AF patients may be one of the potential beneficiary groups for LAAO. However, most previous clinical studies on LAAO were based on small sample sizes to analyze their safety and efficacy, and clinical data on the safety and efficacy of LAAO in this high-risk population of elderly AF patients are still limited. To address this, the study aims to conduct a multicenter randomized controlled trial to compare the efficacy and safety of catheter ablation combined with LAAO versus catheter ablation combined with OAC in elderly AF patients with high bleeding risk, filling the gap in this research area.
To address these limitations, this multicenter randomized controlled trial is designed to evaluate the efficacy and safety of catheter ablation combined with LAAO versus catheter ablation combined with OAC in elderly AF patients at high risk for bleeding. The primary objective of the study is to compare the 12-month incidence and time-to-occurrence of the composite clinical endpoint. This endpoint includes stroke/TIA, systemic embolism, ISTH-defined major bleeding. By establishing these metrics within the first year, the study aims to fill the current void in clinical evidence and provide a standardized treatment strategy for high-risk elderly patients. In addition to the primary endpoints, the study will conduct a comprehensive long-term evaluation extending to 24 months post-procedure to assess the durability of both treatment strategies. Secondary objectives include the assessment of perioperative safety, specifically focusing on serious intraoperative complications and major adverse events occurring within the first seven days after the LAAO procedure. The trial will also measure long-term rhythm control by tracking the rate of freedom from AF recurrence at the one-year and two-year marks. Furthermore, the study seeks to verify the hypothesized superiority of the ablation-plus-LAAO strategy in reducing the specific burden of anticoagulation-related major bleeding and stroke.
Beyond clinical safety and efficacy, the trial will analyze the practical aspects of the two interventions, including procedural success rates, operation duration, fluoroscopy time, and the total duration of hospitalization. A critical component of the research involves identifying specific risk factors associated with complications, with a specialized focus on how frailty scores influence procedural tolerance and long-term prognosis. The study will further explore how different types of AF respond to the LAAO strategy and assess the impact of each treatment on non-major bleeding events. Ultimately, the trial aims to determine which strategy offers a superior improvement in the overall quality of life for elderly patients, thereby optimizing future clinical guidelines.
详细描述
- Study Framework and Design Rationale:
This multicenter randomized controlled trial investigates the efficacy and safety of combining catheter ablation with Left Atrial Appendage Occlusion (LAAO) compared to catheter ablation plus long-term oral anticoagulation (OAC) in a frail elderly population. Given the technical and ethical complexities of blinding invasive surgical procedures and subsequent anticoagulation adjustments, an open-label design is utilized to facilitate individualized post-operative management that reflects real-world clinical practice. 2. Randomization, Enrollment, and Implementation:
Following the signing of the written Informed Consent Form (ICF), potential participants enter a rigorous screening phase to ensure compliance with predefined inclusion and exclusion criteria. Eligible subjects (Target N=200) are randomly assigned in a 1:1 ratio to either the Research Group (Ablation + LAAC) or the Control Group (Ablation + OAC) via a centralized Interactive Web Response System (IWRS). The randomization sequence is generated using SPSS 26.0 with stratified block randomization, using the clinical trial institution as the stratification factor. To minimize bias, the interval between randomization and treatment initiation is strictly targeted to be less than 24 hours. The procedures are performed by operators with over 3 years of experience and a minimum of 100 successful AF ablation and LAAC cases to minimize operator-dependent bias. 3. Comprehensive Baseline and Clinical Assessments:
A multidimensional baseline assessment is conducted, encompassing demographic data (BMI, lifestyle habits), clinical risk scores (CHA₂DS₂-VASc, HAS-BLED), and comprehensive geriatric assessments, including the Clinical Frailty Scale (CFS), cognitive function (MoCA/MMSE), and Activities of Daily Living (ADL). Detailed medical histories are recorded, including specific definitions for stroke types (TIA, RIND, CS), congestive heart failure (regardless of LVEF), peripheral vascular disease, and chronic kidney disease (eGFR <60 mL/min/1.73m² per KDIGO guidelines). Laboratory evaluations at baseline include complete blood counts (WBC, Hb, PLT), coagulation markers (INR, PT, APTT), liver/renal functions, thyroid panels (FT3, FT4, TSH), and cardiac biomarkers (NT-ProBNP/BNP). 4. Surgical Procedures and Follow-up Regimen:
Surgical parameters for catheter ablation (ablation site, power, temperature, and acute pulmonary vein isolation) and LAAC (device brand/size, stability, and residual shunt) are documented in detail. The structured follow-up schedule occurs at 1, 3, 6, 12, and 24 months post-operation. Efficacy and safety monitoring involve 12/15-lead ECGs at every visit and 24-hour Holter monitoring at months 3, 6, 12, and 24 to quantify AF burden and recurrences (duration ≥30s). Imaging studies including Transthoracic Echocardiography (TTE) are performed at 6, 12, and 24 months, while the Research Group undergoes Transesophageal Echocardiography (TEE) or Cardiac CT (CCT) at 3 and 12 months to assess device stability, residual shunts, and Device-Related Thrombus (DRT), which directly informs antithrombotic therapy adjustments. 5. Statistical Analysis Plan and Sample Size Rationale:
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
入排标准
- 年龄范围
- 75 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(1) Age ≥ 75 years. (2) Confirmed diagnosis of non-valvular atrial fibrillation (paroxysmal or persistent). (3) CHA2DS2-VASc score ≥ 3 (high risk of stroke) . (4) Procedure-related criteria: Sequential Group: Participants who have received catheter ablation for non-valvular AF within 90 to 180 days prior to randomization. One-stop Group: Participants who are scheduled to undergo clinically indicated catheter ablation within 10 days after randomization. (5) Judged by the investigator to be able to tolerate the defined antithrombotic drug regimen. (6) Suitable to undergo Transesophageal Echocardiography (TEE) or Pulmonary Vein Computed Tomography (CT). (7) Able and willing to sign the written informed consent form. (8) Willing to return for all scheduled follow-up visits and examinations.
排除标准
- •(1) Presence of thrombus in the left atrium or left atrial appendage identified on preoperative imaging (echocardiogram, pulmonary vein CT, etc). (2) Major bleeding event (per ISTH definition) within 14 days prior to randomization. Participants must be excluded if clinical sequelae persist or if interventions for the bleeding source are planned/pending, regardless of the time elapsed since the event. (3) Requirement for long-term oral anticoagulation (OAC) for reasons other than stroke risk reduction in AF (e.g., underlying hypercoagulable state) that would prevent OAC discontinuation post-device implantation. (4) Any cardiac or major non-cardiac intervention/surgery (excluding AF ablation and cardioversion) performed within 30 days prior to, or scheduled within 60 days after randomization. This includes but is not limited to Percutaneous Coronary Intervention (PCI) or other cardiac ablations. (5) Life expectancy < 2 years, malignancy, infectious endocarditis, uncontrolled infection, or physiological evidence of cardiac tamponade. (6) Clinical Frailty Scale (CFS) score of 1-3 (not frail) or 7-9 (severely frail/terminally ill). (7) Deemed unsuitable for long-term anticoagulation and/or antiplatelet therapy by the investigator due to bleeding risk, allergies, or other reasons. (8) Current participation in another clinical trial that interferes with this study, excluding mandatory government or purely observational registries. (9) Stroke or transient ischemic attack (TIA) within 60 days prior to randomization. (10) Documented myocardial infarction (NSTEMI or STEMI) within 90 days prior to randomization, regardless of intervention. (11) History of atrial septal defect (ASD) repair or presence of an ASD/Patent Foramen Ovale (PFO) occluder. (12) Presence of a mechanical prosthetic valve in any position. (13) Participants of childbearing potential who are pregnant or planning pregnancy during the study period. (14) Medical or anatomical contraindications to percutaneous catheter-based interventions. (15) Documented NYHA Class IV heart failure. (16) History of surgical left atrial appendage (LAA) closure.
- •Transthoracic Echocardiography (TTE) Specific Exclusions: (1) Low LVEF: Left ventricular ejection fraction (LVEF) < 30%. (2) Presence of pericardial effusion with a circumferential echo-free space > 5mm. (3) Presence of high-risk PFO associated with an atrial septal aneurysm (ASA) with an excursion or length > 15mm. (4) Presence of high-risk PFO with a large shunt (defined as appearance of microbubbles within 3 cardiac cycles and/or a substantial count of microbubbles). (5) Presence of moderate or severe mitral stenosis (mitral valve area < 1.5 cm2).
研究组 & 干预措施
catheter ablation combined with LAAO
Participants will receive a combined intervention consisting of catheter ablation for rhythm control and percutaneous left atrial appendage occlusion (LAAO) for stroke prevention. These procedures may be performed either during the same operative session (One-Stop) or as separate. This strategy is used as an alternative to long-term oral anticoagulation in elderly patients with a high risk of bleeding.
干预措施: catheter ablation combined with LAAO (Left Atrial Appendage Occlusion) (Device)
Atrial Fibrillation Radiofrequency Ablation Only
Participants will receive standard-of-care treatment consisting of catheter ablation followed by long-term oral anticoagulation (OAC) for stroke prevention. This arm follows current clinical guidelines to evaluate baseline efficacy and safety outcomes compared to the device-based strategy.
干预措施: Atrial Fibrillation Radiofrequency Ablation Only (Drug)
结局指标
主要结局
Incidence of Net Adverse Clinical Events (NACE) at 12 Months
时间窗: 12 months post-randomization
NACE is defined as a composite endpoint consisting of stroke, systemic embolism, and major bleeding according to the International Society on Thrombosis and Haemostasis (ISTH) criteria. The analysis will measure the time from randomization to the first occurrence of any event within this composite endpoint.
次要结局
- Incidence of All-Cause Mortality(12 months and 24 months post-randomization)
- Incidence of Cardiovascular Mortality(12 months and 24 months post-randomization)
- Incidence of Net Clinical Benefit (NCB) at 24 Months(24 months post-randomization)
- Incidence of Unplanned Readmission(12 months and 24 months post-randomization)
- Cumulative Incidence of Major Bleeding(24 months post-randomization)
- Cumulative Incidence of Thromboembolic Events(24 months post-randomization)
- Incidence of Non-major Bleeding(24 months post-randomization)
- Procedural Success Rate(During the procedure and for the duration of the index hospitalization (up to 7 days post-procedure).)
- Total Procedure and Fluoroscopy Duration(During procedure)
- Length of Index Hospital Stay(From the day of admission for the index procedure through the day of discharge, assessed up to 24 months .)
- Change in Clinical Frailty Scale (CFS) Score(Baseline, 6, 12, 18, and 24 months post-randomization.)
- Change in Atrial Fibrillation Effect on Quality-of-Life (AFEQT) Questionnaire Score(Baseline, 6, 12, 18, and 24 months post-randomization.)
- Change in Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) Scores(Baseline, 6, 12, 18, and 24 months post-randomization.)
- Change in Mini-Mental State Examination (MMSE) or Montreal Cognitive Assessment (MoCA) Score(Baseline, 6, 12, 18, and 24 months post-randomization.)
- Modified Rankin Scale (mRS) Score Following Stroke Event(At stroke occurrence (up to 2 years))
- National Institutes of Health Stroke Scale (NIHSS) Score Following Stroke Event(At stroke occurrence (up to 2 years))
- Days Alive and Out of Hospital (DAOH) within 12 Months(From randomization up to 12 months)
- Incidence of Major Adverse Cardiovascular Events (MACE) by Atrial Fibrillation Subtypes(From randomization up to 24 months)
- Incidence of Acute Major Adverse Events (MAE)(From the index procedure up to 7 days)
- Incidence of Atrial Arrhythmia Recurrence(12 months and 24 months post-randomization)
研究者
Yumei Xue
Director, Guangdong Institute of Geriatrics; Chief Physician, Department of Cardiology
Guangdong Provincial People's Hospital