Effect of Tirzepatide on Recurrence of Atrial Fibrillation After Catheter Ablation in Obese Patients

Официальное название

Effect of Tirzepatide on Recurrence of Atrial Fibrillation After Catheter Ablation in Obese Patients: A Multicenter, Randomized, Open-Label Trial

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Tirzepatide
  Dual GIP and GLP-1 receptor agonist administered as a weekly subcutaneous injection. Titrated from 2.5 mg/week to a target of 10 mg/week over 12 weeks, then maintained at the maximum tolerated dose for the remainder of the 52-week treatment period.
• Поведенческое Structured Lifestyle Intervention
  Guideline-directed AF management (rate/rhythm control, anticoagulation by CHA2DS2-VASc). Structured lifestyle intervention: 500 kcal/day caloric deficit; exercise prescription of ≥150 min/week moderate aerobic; smoking cessation and alcohol moderation counseling.

Первичные конечные точки

• Number of Participants With Recurrence of Atrial Fibrillation, Atrial Flutter, or Atrial Tachycardia [Срок оценки: Day 91 through Week 52 after catheter ablation]

Вторичные конечные точки (9)

• Percentage of Monitoring Time Spent in Atrial Fibrillation (AF Burden) [Срок оценки: At Week 12, Week 26, and Week 52]
• Change in body weight [Срок оценки: Baseline to Week 52]
• Change in BMI [Срок оценки: Baseline to Week 52]
• Change in waist circumference [Срок оценки: Baseline to Week 52]
• Change in left atrial volume index (LAVI) [Срок оценки: Baseline to Week 52]
• Change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) [Срок оценки: Baseline to Week 52]
• Change in Serum High-Sensitivity C-Reactive Protein (hs-CRP) Concentration [Срок оценки: Baseline to Week 52]
• Time to Cardiovascular Death [Срок оценки: Day 1 through Week 52]
• Time to Death From Any Cause [Срок оценки: Day 1 through Week 52]

Критерии участия

Критерии включения

• 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)

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07715929 · TEAR-AF-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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