Effect of Tirzepatide on Recurrence of Atrial Fibrillation After Catheter Ablation in Obese Patients: A Multicenter, Randomized, Open-Label Trial
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 710
- 主要终点
- Number of Participants With Recurrence of Atrial Fibrillation, Atrial Flutter, or Atrial Tachycardia
研究概览
简要总结
Obese patients with atrial fibrillation (AF) have a high recurrence rate after catheter ablation, even at experienced centers. Weight reduction improves post-ablation outcomes, but lifestyle measures alone are difficult to sustain. Tirzepatide, a once-weekly GIP/GLP-1 dual receptor agonist, produces greater weight loss than GLP-1 monotherapy and may confer additional cardiometabolic benefits. This multicenter, randomized, open-label, parallel-group, superiority trial evaluates whether adding standardized tirzepatide treatment to a structured lifestyle intervention - compared with the lifestyle intervention alone - reduces AF recurrence within 1 year after ablation in obese patients.
详细描述
Eligible obese patients (or overweight patients with a weight-related comorbidity) with symptomatic paroxysmal or persistent AF undergoing catheter ablation will be screened within 28 days before the procedure. After ablation with restoration of sinus rhythm, participants will be randomized 1:1 to (a) tirzepatide plus standardized lifestyle intervention and standard AF management, or (b) standardized lifestyle intervention and standard AF management alone. Randomization is stratified by study center, AF type (paroxysmal/persistent), baseline BMI, and diabetes status.
A 90-day post-ablation blanking period (Day 0-90) is excluded from the primary efficacy assessment. The primary efficacy assessment window runs from Day 91 to Day 365. Tirzepatide is administered subcutaneously once weekly and titrated per the China NMPA label using an individualized dose-adjustment SOP, continuing through Week 52. Both groups receive guideline-directed periprocedural anticoagulation, standardized antiarrhythmic drug (AAD) use, an individualized exercise prescription, a modified Mediterranean diet (target intake = total energy expenditure - 500 kcal), and management of smoking, alcohol, comorbidities, sleep, and obstructive sleep apnea (OSA).
Approximately 8-12 tertiary (Class 3A) hospitals in China with mature AF ablation teams will participate. Planned enrollment is 710 participants.
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)
盲法说明
Participants and treating physicians are unmasked. All rhythm events are adjudicated by an independent blinded Clinical Endpoint Committee (CEC).
Imaging and biomarker core laboratories operate in blinded fashion. Statistician is blinded until the primary analysis is locked.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years and ≤75 years at the time of screening
- •Documented symptomatic paroxysmal AF or persistent AF, confirmed by 12-lead ECG, Holter monitoring, or cardiac monitoring device, with documented AF episode duration ≥7 days (for persistent AF) and total AF history duration ≤5 years
- •Body weight criteria (aligned with NMPA-approved tirzepatide indication) meeting at least one of the following:
- •BMI ≥28.0 kg/m² (obesity threshold per Chinese criteria), OR BMI ≥24.0 kg/m² and <28.0 kg/m² (overweight per Chinese criteria) with at least one weight-related comorbidity: hypertension, dyslipidemia, type 2 diabetes mellitus (T2DM), obstructive sleep apnea syndrome (OSAS), or atherosclerotic cardiovascular disease (ASCVD)
- •Failed response to or intolerance of at least one antiarrhythmic drug (AAD), or explicit patient preference for a rhythm control strategy
- •Undergoing catheter ablation for AF at a participating center, with confirmed successful restoration of sinus rhythm at the end of the procedure (as determined by the operator)
- •Willing and able to understand the study procedures, provide written informed consent, and comply with all protocol requirements including 12-month follow-up visits
- •Capable of performing basic physical activity (no absolute contraindication to moderate-intensity aerobic exercise)
排除标准
- •Cardiovascular Exclusion Criteria
- •Long-standing persistent AF: continuous AF duration ≥5 years prior to enrollment
- •Prior catheter ablation for AF or atrial flutter at any time
- •Left atrial anteroposterior diameter >55 mm (by transthoracic echocardiography at screening)
- •Left ventricular ejection fraction (LVEF) <35% at screening
- •NYHA functional class III or IV heart failure
- •Significant structural heart disease: hypertrophic cardiomyopathy, valvular heart disease requiring intervention, congenital heart disease, myocarditis, or cardiac sarcoidosis
- •Acute coronary syndrome (ACS), ischemic stroke/TIA, or major cardiac surgery within 6 months prior to screening
- •Tirzepatide-Specific Exclusion Criteria (per NMPA Prescribing Information)
- •Prior use of any GLP-1 receptor agonist (liraglutide, semaglutide, dulaglutide, exenatide, etc.) or GIP receptor agonist, or known hypersensitivity to tirzepatide or any excipient in the formulation
- •Personal or family (first-degree relative) history of multiple endocrine neoplasia type 2 (MEN2) or medullary thyroid carcinoma (MTC)
- •History of acute pancreatitis or chronic pancreatitis, or current symptomatic cholelithiasis or cholecystitis
- •Type 1 DM
- •Severe gastrointestinal disease including severe gastroparesis, inflammatory bowel disease, or any condition that would substantially impair gastrointestinal motility or absorption
- •General Exclusion Criteria
- •Use of any weight-loss medication (orlistat, phentermine, naltrexone/bupropion, or other anti-obesity agents) or participation in any weight-loss pharmacotherapy clinical trial within 3 months prior to screening
- •Severe hepatic insufficiency (Child-Pugh class C) or severe renal insufficiency (eGFR <15 mL/min/1.73 m²)
- •Active malignancy (receiving systemic anti-cancer treatment or with life expectancy <2 years due to malignancy)
- •Pregnancy, breastfeeding, or women of childbearing potential who are unwilling to use highly effective contraception throughout the study and for ≥1 month after the last dose of tirzepatide
- •Severe psychiatric disorder (schizophrenia, bipolar disorder, severe major depressive disorder) that would impair ability to comply with study procedures
- •Known allergy or sensitivity to adhesive patch materials (relevant to ECG monitoring patch components)
- •Any other condition that, in the opinion of the investigator, would make participation inadvisable or compromise the safety of the participant or the integrity of the study
结局指标
主要结局
Number of Participants With Recurrence of Atrial Fibrillation, Atrial Flutter, or Atrial Tachycardia
时间窗: Day 91 through Week 52 after catheter ablation
Any documented atrial arrhythmia - defined as AF, atrial flutter (AFL), or atrial tachycardia (AT) - lasting ≥30 seconds, in the absence of antiarrhythmic drug (AAD) use.
次要结局
- Percentage of Monitoring Time Spent in Atrial Fibrillation (AF Burden)(At Week 12, Week 26, and Week 52)
- Change in body weight(Baseline to Week 52)
- Change in BMI(Baseline to Week 52)
- Time to Death From Any Cause(Day 1 through Week 52)
- Change in waist circumference(Baseline to Week 52)
- Change in left atrial volume index (LAVI)(Baseline to Week 52)
- Change in N-terminal pro-B-type natriuretic peptide (NT-proBNP)(Baseline to Week 52)
- Change in Serum High-Sensitivity C-Reactive Protein (hs-CRP) Concentration(Baseline to Week 52)
- Time to Cardiovascular Death(Day 1 through Week 52)
研究者
Yunlong Wang
Chief Physician, Professor,
Beijing Anzhen Hospital