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Sponsor: Yunlong Wang
Conditions: Atrial Fibrillation, Obesity & Overweight, Catheter Ablation
Interventions: Tirzepatide, Structured Lifestyle Intervention
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.
Sex: ALL
Age: 18 Years to 75 Years
Healthy volunteers: No
Study type: INTERVENTIONAL
Inclusion Criteria: * 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) Exclusion Criteria: 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