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

NCT07715929 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: TEAR-AF-01
• Study Type: interventional
• Target: 710
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Catheter Ablation; Atrial Fibrillation; Obesity & Overweight

Keywords

Atrial Fibrillation; Tirzepatide; GIP/GLP-1 receptor agonist

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Recurrence of Atrial Fibrillation, Atrial Flutter, or Atrial Tachycardia

  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.

  Day 91 through Week 52 after catheter ablation

Secondary Outcomes (9)

• 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

• Change in waist circumference

  Baseline to Week 52

• Change in left atrial volume index (LAVI)

  Baseline to Week 52

Other Outcomes (1)

• Change in epicardial adipose tissue volume

  Baseline to Week 52

Study Arms (2)

Tirzepatide + Lifestyle Intervention

EXPERIMENTAL

Standardized lifestyle intervention and standard AF management plus once-weekly subcutaneous tirzepatide, initiated after randomization and continued through Week 52. Tirzepatide titration (per NMPA label): * Weeks 1-4: 2.5 mg once weekly (initiation) * Weeks 5-16: escalate by 2.5 mg every 4 weeks (5 mg → 7.5 mg → 10 mg) * Weeks 17-52: maintenance 10 mg once weekly, up-titratable to 15 mg (maximum dose 15 mg)

Drug: Tirzepatide; Behavioral: Structured Lifestyle Intervention

Lifestyle Intervention

ACTIVE COMPARATOR

AF Management and Post-Ablation Care * Ablation technique: circumferential pulmonary vein isolation (CPVI) ± adjunctive linear ablation at operator discretion, using established mapping and energy delivery protocols * Peri-procedural anticoagulation: guideline-directed anticoagulation * Antiarrhythmic drug (AAD) use: standardized per protocol SOP; Exercise Intervention • Target: moderate-intensity aerobic exercise ≥150 minutes per week, OR vigorous-intensity aerobic exercise ≥75 minutes per week Dietary Intervention • Caloric target: estimated total energy expenditure (TEE) minus 500 kcal/day Other Risk Factor Management * Smoking cessation * Alcohol restriction * Comorbidity management * OSA management

Behavioral: Structured Lifestyle Intervention

Interventions

Tirzepatide DRUG

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.

Also known as: Mounjaro

Tirzepatide + Lifestyle Intervention

Structured Lifestyle Intervention BEHAVIORAL

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.

Lifestyle Intervention; Tirzepatide + Lifestyle Intervention

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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
• 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
• 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)

Sponsors & Collaborators

• Yunlong Wang: lead

MeSH Terms

Conditions

Atrial Fibrillation; Obesity; Overweight

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Physician, Professor,

Study Record Dates

• First Submitted: July 15, 2026
• First Posted: July 21, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): December 30, 2029
• Last Updated: July 21, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Beginning 12 months after publication of the primary results, ending 5 years thereafter.
• Access Criteria: Requests reviewed by the trial steering committee. Investigators must submit a methodologically sound proposal, have approval from an independent review committee, and sign a data use agreement.