Atrial FibrillationPhase 4TEAR-AF-HFpEFNCT07630454
Tirzepatide on Atrial Fibrillation Recurrence After Catheter Ablation in Patients With Obesity and HFpEF
A Phase 4 study testing Tirzepatide and Structured Lifestyle Intervention in people with Atrial Fibrillation and Heart Failure With Preserved Ejection Fraction (HFpEF), run by Yunlong Wang at 1 site in China.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Atrial Fibrillation, Heart Failure With Preserved Ejection Fraction (HFpEF), Tirzepatide
- What is being tested?
- Tirzepatide and Structured Lifestyle Intervention
- Type of treatment
- Injection or infusion, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 602 participants
- Where
- 1 siteChina
- Study dates
- 1 Aug 2026to 1 Dec 2029
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Beijing Anzhen Hospital
Beijing, Beijing Municipality, 100029
wang_lili1002@163.com
About this study
Official title: Effect of Tirzepatide on Recurrence of Atrial Fibrillation After Catheter Ablation in Patients With Obese and HFpEF: A Randomized Controlled Trial
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.
Read the detailed description
Background and Rationale: Obesity and HFpEF are key drivers of AF onset and recurrence. In patients with both conditions, 12-month AF recurrence after catheter ablation reaches 40-55%. The LEGACY and ARREST-AF cohorts demonstrated that ≥10% weight loss approximately halves AF recurrence. Tirzepatide, a dual GIP/GLP-1 receptor agonist, achieved over 20% weight reduction in SURMOUNT-1 and improved heart failure outcomes in the SUMMIT trial of HFpEF with obesity. Whether tirzepatide reduces post-ablation AF recurrence has not been prospectively tested. TEAR-AF-HFpEF enrolls a population most likely to benefit mechanistically - obesity plus HFpEF - and tests the hypothesis with a hemodynamically defined HFpEF cohort.
Study Design: Multicenter randomized open-label parallel-group blinded-endpoint superiority trial. Eligible patients are randomized 1:1 within 48 hours of ablation, stratified by site, AF type (paroxysmal vs persistent), and BMI.
Intervention:
Tirzepatide arm: weekly subcutaneous tirzepatide starting at 2.5 mg/week with monthly 2.5 mg dose escalation to a target of 10 mg/week, advanced to 15 mg/week if tolerated, for 12 months.
Control arm: standard care without GLP-1 class drugs. Both arms receive identical structured lifestyle intervention (≥150 min/week moderate aerobic activity, sleep apnea screening), and standard-of-care guideline-directed therapies for AF, anticoagulation, and HFpEF.
Sample Size and Statistical Approach: A total of 602 participants (301 per arm) provides 80% power at two-sided α = 0.05, assuming 15% loss to follow-up. The primary analysis is an intention-to-treat Kaplan-Meier comparison with log-rank test and Cox proportional hazards modeling stratified by randomization factors.
- Being tested
- Tirzepatide, Structured Lifestyle Intervention
- Keywords
- Atrial Fibrillation, Tirzepatide, GIP/GLP-1 receptor agonist, Obesity, HFpEF
- Medical subject headings
- Atrial Fibrillation, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TirzepatideDrug
Also called Mounjaro
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.
Structured Lifestyle InterventionBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Behavioral: Structured Lifestyle Intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Day 91 through Week 52 after catheter ablation
Secondary outcomes (12)
Percentage of Monitoring Time Spent in AF (AF Burden)
Percentage of total monitoring time spent in AF, measured by 7-day ambulatory ECG patch.
Measured: At Week 12, Week 26, and Week 52
Change in body weight
Absolute and percentage change in body weight (kg) from baseline to 52 weeks.
Measured: Baseline to Week 52
Change in body mass index (BMI)
Change from baseline to 52 weeks in BMI (kg/m²)
Measured: Baseline to Week 52
Change in waist circumference
Change from baseline to 52 weeks in waist circumference (cm).
Measured: Baseline to Week 52
Change in left atrial volume index (LAVI)
Change in echocardiographic LAVI (mL/m²) from baseline to 52 weeks, measured by core laboratory
Measured: Baseline to Week 52
Change in Echocardiographic E/e' Ratio
Change in echocardiographic E/e' from baseline to 52 weeks, measured by core laboratory.
Measured: Baseline to Week 52
Time to First Hospitalization for Heart Failure
Time to first hospitalization for heart failure, adjudicated by the CEC.
Measured: Day 1 through Week 52
Time to Cardiovascular Death
Time to cardiovascular death
Measured: Day 1 through Week 52
Time to Death From Any Cause
Time to death from any cause.
Measured: Day 1 through Week 52
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score
Change in KCCQ overall summary score and clinical summary score from baseline to 52 weeks. Both scores range from 0 to 100, with higher scores indicating better health status (fewer symptoms, less physical limitation, and better quality of life).
Measured: Baseline to Week 52
Change in Serum NT-proBNP Concentration
Change in serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration from baseline to 52 weeks, measured by central laboratory.
Measured: Baseline to Week 52
Change in Serum High-Sensitivity C-Reactive Protein (hs-CRP) Concentration
Change in serum hs-CRP concentration from baseline to 52 weeks, measured by central laboratory.
Measured: Baseline to Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2026
- Study start1 Aug 2026 (estimated)
- Primary completion1 Aug 2029 (estimated)
- Study completion1 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 602 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yunlong Wang
- Sponsor type
- University, hospital or other
- Collaborators
- Shanghai Zhongshan Hospital
- Responsible party
- Sponsor-investigator, Yunlong Wang, Beijing Anzhen Hospital
- Investigators
- Yunlong Wang, PHD, Principal investigator, Beijing Anzhen Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07630454
- Sponsor's protocol ID
- TEAR-AF-HFpEF_V1
- Acronym
- TEAR-AF-HFpEF
- Status last verified
- Jun 2026
- First submitted
- 27 May 2026
- Last updated
- 5 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual de-identified participant data underlying the published results, together with the study protocol, statistical analysis plan, and data dictionary, will be made available upon reasonable request after publication of the primary results.