Tirzepatide on Atrial Fibrillation Recurrence After Catheter Ablation in Patients With Obesity and HFpEF

NCT07630454 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: TEAR-AF-HFpEF_V1
• Study Type: interventional
• Target: 602
• Locations: 1 country
• Sites: 1

Brief Summary

This multicenter, randomized, open-label, blinded-endpoint trial evaluates whether weekly subcutaneous tirzepatide for 12 months reduces atrial fibrillation (AF) recurrence after catheter ablation in adults with obesity and heart failure with preserved ejection fraction (HFpEF). HFpEF is diagnosed by direct intraprocedural measurement of mean left atrial pressure (mLAP ≥ 15 mmHg at rest) during the ablation procedure, providing a hemodynamically anchored, homogeneous study population free from the diagnostic ambiguities of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and E/e' in AF patients. Approximately 602 participants will be randomized 1:1 to tirzepatide (titrated to a target of 10 mg/week, maximum 15 mg/week) plus standard care, or standard care alone. Both groups receive an identical structured lifestyle intervention. The primary endpoint is the first documented AF/atrial flutter/atrial tachycardia episode lasting ≥ 30 seconds, occurring between day 91 and day 365 after ablation, adjudicated by an independent blinded clinical endpoint committee.

Conditions

Atrial Fibrillation; Tirzepatide; Heart Failure With Preserved Ejection Fraction (HFpEF)

Keywords

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

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 (12)

• Percentage of Monitoring Time Spent in AF (AF Burden)

  At Week 12, Week 26, and Week 52

• Change in body weight

  Baseline to Week 52

• Change in body mass index (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

Participants receive subcutaneous tirzepatide once weekly for 12 months in addition to guideline-directed lifestyle intervention. Dose escalation: 2.5 mg/week for weeks 1-4; 5 mg/week for weeks 5-8; 7.5 mg/week for weeks 9-12; 10 mg/week from week 13 onward (target); may be escalated to 15 mg/week if tolerated. All participants additionally receive a structured lifestyle intervention identical to the control arm.

Drug: Tirzepatide; Behavioral: Structured Lifestyle Intervention

Lifestyle Intervention

ACTIVE COMPARATOR

Participants receive guideline-directed standard care for AF, anticoagulation, and HFpEF, without any GLP-1 receptor agonist or GIP/GLP-1 dual agonist. The same structured lifestyle intervention as the experimental arm is delivered, including monthly dietitian-led counseling, exercise prescription, and sleep apnea screening, to ensure equal follow-up intensity.

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 (maximum 15 mg/week) over 12 weeks, then maintained at the maximum tolerated dose for the remainder of the 12-month treatment period.

Also known as: Mounjaro

Tirzepatide + Lifestyle Intervention

Structured Lifestyle Intervention BEHAVIORAL

Guideline-directed AF management (rate/rhythm control, anticoagulation by CHA2DS2-VASc). Guideline-directed HFpEF therapy (MRA, SGLT2 inhibitor as clinically indicated). Structured lifestyle intervention: monthly dietitian-led counseling targeting a 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 - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 80 years
• Symptomatic atrial fibrillation (paroxysmal or persistent of ≤ 5 years duration), undergoing first-time catheter ablation
• 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)
• HFpEF defined by intraprocedural mean left atrial pressure ≥ 15 mmHg at rest
• Left ventricular ejection fraction ≥ 50% on echocardiography within 30 days prior to enrollment
• Provision of written informed consent

You may not qualify if:

• Prior use of any GLP-1 receptor agonist or GIP/GLP-1 dual receptor agonist
• Type 1 diabetes mellitus; or type 2 diabetes with HbA1c \> 10%
• Personal history of pancreatitis; personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN2)
• Severe gastrointestinal disease, including gastroparesis or active inflammatory bowel disease
• Prior bariatric surgery
• Moderate or severe valvular heart disease, hypertrophic cardiomyopathy, cardiac amyloidosis, constrictive pericarditis, or restrictive cardiomyopathy
• Severe renal impairment (eGFR \< 30 mL/min/1.73m²)
• Active malignancy, excluding basal cell carcinoma
• Acute coronary syndrome, stroke, percutaneous coronary intervention, or cardiac surgery within 30 days prior to enrollment
• Pregnancy, lactation, or planned pregnancy within 6 months
• Life expectancy \< 12 months
• Concurrent participation in another interventional clinical trial
• Any condition that, in the investigator's judgment, would interfere with participation

Sponsors & Collaborators

• Yunlong Wang: lead
• Shanghai Zhongshan Hospital: collaborator

Study Sites (1)

Beijing Anzhen Hospital

Beijing, Beijing Municipality, 100029, China

Location

MeSH Terms

Conditions

Atrial Fibrillation; Obesity

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Overweight; 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 Officials

• Yunlong Wang, PHD

  Beijing Anzhen Hospital

  PRINCIPAL INVESTIGATOR

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: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Physician; Professor;

Study Record Dates

• First Submitted: May 27, 2026
• First Posted: June 5, 2026
• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: June 5, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• 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.

Locations

CN (1)