Finerenone for Reducing Atrial Fibrillation Recurrence After Pulmonary Vein Isolation: A Randomized Pilot Trial With Mechanistic Assessment of Epicardial Adipose Tissue Remodeling and Brown Adipose Tissue Activation
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Atrial fibrillation recurrence after the blanking period
研究概览
简要总结
Atrial fibrillation (AF) is a common heart rhythm disorder associated with stroke, heart failure, and increased mortality. Catheter ablation with pulmonary vein isolation (PVI) is an effective rhythm-control strategy, but 20-30% of patients experience AF recurrence within one year. Finerenone, a nonsteroidal mineralocorticoid receptor antagonist with anti-inflammatory, antifibrotic, and metabolic effects, was associated with a lower incidence of AF in prior large trials, and preclinical studies suggest it promotes "browning" of adipose tissue and improves epicardial adipose tissue (EAT) characteristics.
This single-center, randomized, investigator-blinded pilot trial will enroll 40 patients undergoing first-time catheter ablation for AF. After successful PVI, participants will be randomized 1:1 to receive finerenone or usual care for 12 months. The primary endpoint is AF recurrence (any atrial arrhythmia episode lasting 30 seconds or longer) after a 90-day blanking period, within 12 months post-ablation. Mechanistic endpoints include EAT remodeling assessed by cardiac computed tomography and echocardiography, and circulating uncoupling protein-1 (UCP1) levels as a biomarker of adipose tissue browning.
The investigators hypothesize that finerenone will lower AF recurrence after ablation, partly through modulation of EAT function.
详细描述
This is a concept-generating study comprising three components: (1) a randomized controlled trial testing whether adjunctive finerenone after catheter ablation reduces AF recurrence compared with usual care; (2) cardiac CT to characterize the EAT phenotype before and after finerenone treatment; and (3) evaluation of whether serum UCP1 levels track brown/ epicardial adipose tissue remodeling and whether changes in UCP1 relate to outcomes after AF ablation.
All participants will undergo AF ablation with radiofrequency or pulsed field ablation for pulmonary vein isolation (wide antral circumferential ablation recommended). In persistent AF, posterior wall isolation may be added at the physician's discretion. After confirmation of entrance and exit block, participants will be randomized 1:1 (computer-generated sequence, stratified by left atrial diameter and AF type [paroxysmal vs nonparoxysmal]) to finerenone or usual care.
Finerenone dosing: 10 mg once daily if eGFR 25-<60 mL/min/1.73 m2; 20 mg once daily if eGFR >=60 mL/min/1.73 m2; up-titration at Week 4 where applicable if serum potassium <=4.8 mmol/L. Treatment duration: 12 months.
Follow-up visits occur at 2 weeks, 1, 3, 6, 9, and 12 months. Antiarrhythmic drugs are permitted during the 90-day blanking period with discontinuation encouraged thereafter. Rhythm monitoring includes 24-hour Holter at baseline, 3, 6, and 12 months, and additional monitoring for symptoms. Transthoracic echocardiography (including left atrial strain and EAT thickness) is performed at baseline, 6, and 12 months; cardiac CT (EAT volume, mean attenuation, and density dispersion) at baseline and 12 months. Blood biomarkers (UCP1, NT-proBNP, hsCRP, TGF-beta, PINP, PIIINP) are measured at baseline, 1, 6, and 12 months.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-80 years
- •Atrial fibrillation scheduled for first-time catheter ablation (pulmonary vein isolation)
- •Estimated glomerular filtration rate (eGFR) >=25 mL/min/1.73 m2
- •Serum potassium <=5.0 mmol/L
排除标准
- •History of prior catheter-based or surgical pulmonary vein isolation
- •Current use of other mineralocorticoid receptor antagonists (MRAs)
- •Severe renal impairment (eGFR <25 mL/min/1.73 m2)
- •Serum potassium >5.0 mmol/L
- •Severe liver disease (Child-Pugh class C)
- •Known hypersensitivity to the investigational drug
- •Contraindications to the investigational drug, such as concomitant use of strong CYP3A4 inducers (e.g., rifampicin, carbamazepine, phenytoin, phenobarbital)
- •Active cancer or recent chemotherapy
- •Women who are pregnant, breastfeeding, or planning to become pregnant during the study period
研究组 & 干预措施
Finerenone
Following successful pulmonary vein isolation, participants receive finerenone once daily for 12 months in addition to standard post-ablation care. Starting dose: 10 mg QD if eGFR 25-<60 mL/min/1.73 m2, 20 mg QD if eGFR >=60 mL/min/1.73 m2; up-titration to 20 mg QD at Week 4 where applicable if serum potassium <=4.8 mmol/L.
干预措施: Finerenone (Drug)
Usual care
Following successful pulmonary vein isolation, participants receive standard-of-care post-ablation management without finerenone.
结局指标
主要结局
Atrial fibrillation recurrence after the blanking period
时间窗: From day 91 (end of the 90-day blanking period) to 12 months after ablation
Proportion of participants with any documented atrial arrhythmia episode (AF, atrial flutter, or atrial tachycardia) lasting \>=30 seconds, detected by 24-hour Holter monitoring, 12-lead ECG, or symptom-triggered monitoring, occurring after the 90-day blanking period.
次要结局
- Time to first atrial fibrillation recurrence(From day 91 to 12 months after ablation)
- Atrial fibrillation burden(3, 6, and 12 months)
- Use of antiarrhythmic drugs after the blanking period(From day 91 to 12 months after ablation)
- Repeat ablation or cardioversion(Up to 12 months after ablation)
- Hospitalization(Up to 12 months after ablation)
- Safety: incidence of adverse events(Up to 12 months after ablation)
- Change in epicardial adipose tissue volume on cardiac CT(Baseline to 12 months)
- Change in epicardial adipose tissue mean attenuation on cardiac CT(Baseline to 12 months)
- Change in serum uncoupling protein-1 (UCP1) concentration by ELISA(Baseline, 1 month, 6 months, and 12 months)
- Change in left atrial strain parameters by two-dimensional speckle-tracking echocardiography(Baseline, 6 months, and 12 months)