Assessment of the Effect of Catheter Ablation on Elderly Population With Atrial Fibrillation; a Randomized Controlled Study; The ACE-AF Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 282
- 试验地点
- 1
- 主要终点
- Change in RAND-36 General Health score
研究概览
简要总结
ACE-AF is a multicenter randomized study in people aged 78 years and older with symptomatic atrial fibrillation (AF). AF is a common heart rhythm disorder in older adults and can cause reduced quality of life and lead to serious complications such as stroke and heart failure.
The study compares two established treatment strategies:
- Catheter ablation (an invasive procedure aimed at reducing AF by electrically isolating triggers in the heart, primarily through pulmonary vein isolation), and
- Optimized medical therapy without AF ablation (medications for rate and/or rhythm control; AV node ablation with pacemaker may be used if clinically indicated according to routine care).
Participants are randomized 1:1 to one of these strategies. All participants will receive an implantable loop recorder (a small heart rhythm monitor placed under the skin) to continuously track heart rhythm and measure AF burden over time.
The study has two primary endpoints, tested with Holm-Bonferroni multiplicity control assessed over 24 months:
- a composite of major clinical events (all-cause mortality, stroke, major bleeding, cardiac arrest, or hospitalization due to heart failure), and
- patient-reported health-related quality of life (HRQoL), measured by the RAND-36 "General Health" domain.
ACE-AF will provide evidence to guide treatment decisions for very elderly patients with symptomatic AF and help identify which patients benefit most from an ablation-based strategy compared with optimized medical therapy.
详细描述
Background and Rationale
Atrial fibrillation (AF) is highly prevalent in very elderly individuals and is associated with substantial morbidity, including stroke, heart failure (HF), recurrent hospitalisations, polypharmacy, frailty, and impaired health-related quality of life (HRQoL). Catheter ablation is an established rhythm-control therapy in AF, but patients aged ≥78 years have been under-represented in randomised trials, and evidence on comparative effectiveness and safety versus optimised medical therapy in this age group remains limited. ACE-AF is designed to address this knowledge gap using a pragmatic randomised strategy design and continuous rhythm monitoring in both arms.
Study Design
ACE-AF is an investigator-initiated, multicentre, parallel-group, open-label randomised controlled trial conducted at seven Swedish university hospitals and collaborating centres in Denmark, Australia and Greece. Participants aged ≥78 years with symptomatic paroxysmal or persistent AF are randomised 1:1 to an ablation-based strategy or to optimised medical therapy without AF ablation.
Randomisation is performed centrally using an electronic system with allocation concealment until assignment, stratified by sex and age group (78-83 vs >83 years).
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
盲法说明
Open-label due to the nature of the interventions (catheter ablation vs optimized medical therapy). Endpoint definitions and event documentation are standardized per protocol.
入排标准
- 年龄范围
- 78 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥78 years.
- •ECG-documented atrial fibrillation.
- •AF type: paroxysmal, persistent, or longstanding persistent AF.
- •Suitable candidate for catheter ablation according to ESC guidelines.
- •Charlson's comorbidity index ≤7.
排除标准
- •Left atrial (LA) dimension >55 mm, based on echocardiography within the previous year.
- •Acute coronary syndrome or coronary artery bypass surgery within the last 12 weeks.
- •Severe valvular heart disease (per ESC definitions) or congenital heart disease.
- •Prior surgical or catheter AF ablation procedure, or prior AV-node (atrioventricular nodal) ablation.
- •Contraindication to oral anticoagulation.
- •AF due to a reversible cause.
- •Medical condition likely to limit survival to <12 months.
- •Unable or unwilling to provide informed consent.
- •History of non-compliance with medical therapy.
- •BMI <18 or >37 kg/m².
研究组 & 干预措施
Catheter Ablation Strategy
Participants randomized to this arm will undergo catheter ablation for atrial fibrillation, with pulmonary vein isolation (PVI) prioritized as the primary ablation strategy. Energy source and tools are selected according to local practice and operator discretion (no restriction to a specific technology). Participants will also receive an implantable loop recorder (ILR) for continuous rhythm monitoring throughout follow-up. Additional medical therapy may be used as clinically indicated according to guideline-based care.
干预措施: Optimized Medical Therapy for Atrial Fibrillation (Drug)
Catheter Ablation Strategy
Participants randomized to this arm will undergo catheter ablation for atrial fibrillation, with pulmonary vein isolation (PVI) prioritized as the primary ablation strategy. Energy source and tools are selected according to local practice and operator discretion (no restriction to a specific technology). Participants will also receive an implantable loop recorder (ILR) for continuous rhythm monitoring throughout follow-up. Additional medical therapy may be used as clinically indicated according to guideline-based care.
干预措施: Catheter Ablation for Atrial Fibrillation (Procedure)
Catheter Ablation Strategy
Participants randomized to this arm will undergo catheter ablation for atrial fibrillation, with pulmonary vein isolation (PVI) prioritized as the primary ablation strategy. Energy source and tools are selected according to local practice and operator discretion (no restriction to a specific technology). Participants will also receive an implantable loop recorder (ILR) for continuous rhythm monitoring throughout follow-up. Additional medical therapy may be used as clinically indicated according to guideline-based care.
干预措施: Implantable Loop Recorder (ILR) (Device)
Optimized Medical Therapy (Rate/Rhythm control) ± AV Node Ablation + Pacing
Participants randomized to this arm will receive optimized guideline-directed medical therapy for atrial fibrillation without AF catheter ablation. Treatment may include rate control and/or rhythm control (including antiarrhythmic drugs and/or cardioversion when clinically appropriate). AV node ablation with pacemaker implantation is permitted when clinically indicated according to routine care. Participants will also receive an implantable loop recorder (ILR) for continuous rhythm monitoring throughout follow-up.
干预措施: Optimized Medical Therapy for Atrial Fibrillation (Drug)
Optimized Medical Therapy (Rate/Rhythm control) ± AV Node Ablation + Pacing
Participants randomized to this arm will receive optimized guideline-directed medical therapy for atrial fibrillation without AF catheter ablation. Treatment may include rate control and/or rhythm control (including antiarrhythmic drugs and/or cardioversion when clinically appropriate). AV node ablation with pacemaker implantation is permitted when clinically indicated according to routine care. Participants will also receive an implantable loop recorder (ILR) for continuous rhythm monitoring throughout follow-up.
干预措施: AV Node Ablation With Pacemaker implantation (Procedure)
结局指标
主要结局
Change in RAND-36 General Health score
时间窗: Baseline to 24 months after intervention (visit 2)
Second part of the co-primary outcome: Change from baseline in the RAND-36 "General Health" domain score at 24 months after the intervention (visit 2). Scores range 0-100; higher scores indicate better perceived health. Intention-to-treat. Because HRQoL is undefined after death, scores are not imputed for participants who die before the 24-month assessment; instead, deceased participants are assigned the worst rank (worst-rank / composite estimand, ICH E9(R1)) and the primary comparison uses a rank-based test. Missing data other than death are handled under a missing-at-random assumption with pre-specified sensitivity analyses.
Composite clinical endpoint (all-cause mortality, stroke, serious bleeding, cardiac arrest, or heart failure hospitalization)
时间窗: 24 months after intervention (visit 2)
First part of the co-primary outcome: Proportion of participants with ≥1 of the following events within 24 months after intervention (visit 2): all-cause death, stroke, serious bleeding, cardiac arrest, or hospitalization for heart failure. Events will be adjudicated per protocol.
次要结局
- Differences of atrial fibrillation and atrial tachycardia burden (ILR-derived) between groups(From date of ILR implantation (intervention day, visit 2) up to 30 months after implantation.)
- Hospitalizations (all-cause and cardiovascular)(Up to 24 months after intervention)
- Serious adverse events and treatment-related complications(Up to 24 months after intervention)
- Additional patient-reported outcomes (AF symptoms / disease-specific HRQoL)(Baseline and follow-up (3, 12, 18) through 24 months after intervention)
- Changes in Left atrial reservoir strain (LASr)(Up to 12 months after intervention (visit 2))
- Cognitive function measured by Montreal Cognitive Assessment (MoCA)(MoCA scores will be collected and assessed at baseline, 12, 18, and 24 months after intervention (visit 2).)
- Frailty score assessed by e-Frailty index(Up to 24 months after intervention; visit 2 ( 12, 18, and 24 months))
- Discrimination of a prediction model for the ACE-AF primary composite outcome(From baseline up to 24 months after intervention (visit 2).)
- Predictors of differential treatment effect on AF/AT burden(From implantation (visit 2) up to 30 months after intervention)
- Participants with at least one event in the composite neurological endpoint (dementia, stroke, intracranial hemorrhage)(Up to 24 months after intervention (visit 2).)
- Total healthcare costs per participant(Up to 24 months after intervention (visit 2))
- All-cause mortality, stroke/TIA, serious bleeding, cardiac arrest, hospitalization due to heart failure analyzed separately(Up to 24 months after intervention)
- Incident dementia(Up to 24 months after intervention (visit 2))
研究者
Emmanouil Charitakis
MD, PhD
Karolinska University Hospital