Catheter Ablation Plus LAAO Versus Anticoagulation in Frail Elderly Patients With Atrial Fibrillation
CLEAR-AF
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
1 other identifier
interventional
200
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Mar 2026
Typical duration for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 25, 2026
CompletedFirst Posted
Study publicly available on registry
March 2, 2026
CompletedStudy Start
First participant enrolled
March 24, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 1, 2028
June 8, 2026
May 1, 2026
1.1 years
January 25, 2026
June 5, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Incidence of Net Adverse Clinical Events (NACE) at 12 Months
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.
12 months post-randomization
Secondary Outcomes (20)
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
- +15 more secondary outcomes
Study Arms (2)
catheter ablation combined with LAAO
EXPERIMENTALParticipants 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.
Atrial Fibrillation Radiofrequency Ablation Only
ACTIVE COMPARATORParticipants 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.
Interventions
1. Ablation: CPVI will be performed using the EnSite X system and HD Grid catheter. Additional linear ablation (e.g., mitral isthmus or roof lines) may be added based on the patient's atrial substrate if sinus rhythm is not restored. LAAO: An LAA closure device (Watchman FLX, LAmbre, or LACbes) will be implanted under TEE or ICE guidance. 2. Antithrombotic Regimen: Days 0-90: Participants receive OAC (NOAC or Warfarin). Day 90 to 12 Months: If imaging confirms no DRT and no residual leak ≥ 5 mm, therapy will be de-escalated (e.g., to aspirin monotherapy) at the investigator's discretion.
Atrial Fibrillation Radiofrequency Ablation: Procedures will be performed using the EnSite X 3D mapping system with an HD Grid high-density mapping catheter for atrial modeling, followed by pulmonary vein isolation using any approved ablation catheter. Linear ablation may be added if necessary. Guideline-directed oral anticoagulation (e.g., NOACs or warfarin) will be continued post-procedure.
Eligibility Criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Guangdong Provincial People's Hospitallead
- Abbott (China)collaborator
Study Sites (1)
Guangdong Provincial People's Hospital
Guangzhou, Guangdong, 510080, China
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Director, Guangdong Institute of Geriatrics; Chief Physician, Department of Cardiology
Study Record Dates
First Submitted
January 25, 2026
First Posted
March 2, 2026
Study Start
March 24, 2026
Primary Completion (Estimated)
May 1, 2027
Study Completion (Estimated)
March 1, 2028
Last Updated
June 8, 2026
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Beginning 6 months and ending 36 months following article publication.
- Access Criteria
- Data will be available to researchers providing a methodologically sound proposal and with signed data access agreement.
Individual participant data that underlie the results reported in the article, after de-identification, will be shared with researchers whose proposed use of the data has been approved.