Atrial Fibrillation (AF), Ablation Treatment, Obesity & Overweight, Mazdutide
Conditions
Keywords
atrial dibrillation, Catheter ablation, Obesity, Mazdutide
Brief summary
This is a multicenter, open-label, superiority randomized controlled trial enrolling adult patients aged 18 to 75 years. All participants have abdominal obesity (BMI ≥ 28 kg/m² with specific waist circumference standards) and non-valvular atrial fibrillation, and have successfully regained normal heart rhythm after their first catheter ablation. The study aims to compare the efficacy and safety of weekly mazdutide injection with conventional routine care in preventing heart rhythm recurrence within 12 months after ablation (excluding a 3-month early recovery blanking period). A total of 24 months will be spent recruiting participants, followed by a 12-month follow-up period. Participants are randomly divided into two groups. The intervention group receives escalating-dose mazdutide subcutaneous injections starting within 48 hours after ablation alongside standard health guidance on diet, exercise and lifestyle. The control group only receives the same routine health guidance without mazdutide treatment. The primary efficacy endpoint is recurrence of atrial arrhythmias (including AF, atrial flutter, and atrial tachycardia) recorded on a standard 12-lead surface ECG for ≥10 seconds, or on a 24-hour Holter monitor (including single-lead ECG patches) for \>30 seconds, at 12 months after a single ablation procedure (after a 3-month blanking period), without the use of any Class I/III antiarrhythmic drugs (AADs).
Interventions
DRUGMazdutide
1. Initiation of mazdutide subcutaneous injection within 48 hours after catheter ablation. Starting dose: 2 mg subcutaneously once weekly using a single-dose pen auto-injector. The initial dose is 2 mg once weekly, increased by 2 mg every 4 weeks during dose escalation, with a maximum dose of 6 mg. The target dose is individualized based on the patient's weight-loss effect. Once the patient achieves a 10% reduction in body weight, the dose is maintained for continued treatment. 2. Patients receive health guidance before discharge, including diet, exercise, smoking cessation, and alcohol abstinence.
OTHERConventional treatment
Patients receive health guidance before discharge, including diet, exercise, smoking cessation, and alcohol abstinence.
Sponsors
Beijing Anzhen Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Aged 18-75 years (inclusive); 2. BMI ≥ 28 kg/m², with waist circumference ≥ 90 cm for male subjects and ≥ 85 cm for female subjects; 3. Patients with non-valvular atrial fibrillation (AF) undergoing their first AF catheter ablation and maintaining sinus rhythm within 24 hours post-ablation; 4. Anteroposterior diameter of the left atrium (excluding transverse and superoinferior diameters) measured from the parasternal long-axis view on echocardiography \< 55 mm; 5. Agree to randomization as specified in this study and be able to complete follow-up assessments as required.
Exclusion criteria
\### Surgery-related 1. AF caused by reversible etiologies; 2. Left ventricular ejection fraction (LVEF) \< 30 % on echocardiography; 3. Unstable angina, acute myocardial infarction, or percutaneous coronary intervention (PCI) within the preceding 1 month; 4. Patients with severe coronary artery stenosis without prior PCI; 5. Stroke, transient ischemic attack (TIA), intracerebral hemorrhage, or any embolic event within the preceding 1 month; 6. Severe congenital heart disease, such as tetralogy of Fallot, corrected transposition of the great arteries, etc.; 7. Hypertrophic cardiomyopathy; 8. Moderate or greater aortic stenosis, moderate or greater mitral stenosis; 9. Severe hepatic dysfunction (Child-Pugh Class 3), renal insufficiency (eGFR \< 30 mL/min/1.73 m²), or a history of renal dialysis, kidney transplantation, or nephrectomy; 10. Prior cardiac surgery, including coronary artery bypass grafting, mechanical or bioprosthetic valve replacement, etc.; 11. Post-implantation of intracardiac devices, such as pacemaker implantation, left atrial appendage closure, patent foramen ovale closure, atrial septal defect transcatheter closure, etc.; 12. Contraindications to anticoagulant therapy; 13. Presence of an inferior vena cava filter, or contraindications to right- or left-heart catheterization (e.g., left atrial thrombus, etc.). \### Medications or treatments received prior to screening 14. Self-reported body weight change \> 5 % within 90 days before screening; 15. Use (past or current) of anti-obesity medications within 90 days before screening, including sibutramine hydrochloride, orlistat, phentermine, phenylpropanolamine, mazindol, diethylpropion, lorcaserin, phentermine-topiramate combination, naltrexone-bupropion combination, and GLP-1 receptor agonists (liraglutide, benaglutide, semaglutide, tirzepatide, mazdutide), etc.; 16. Use of weight-altering medications within 90 days before screening: systemic corticosteroids (intravenous, oral, or intra-articular administration), tricyclic antidepressants, psychotropic or sedative agents (e.g., imipramine, amitriptyline, mirtazapine, paroxetine, phenelzine, chlorpromazine, thioridazine, clozapine, olanzapine, valproic acid and its derivatives, lithium salts), etc.; 17. Use of weight-modulating Chinese herbal medicines, health supplements, or meal replacements within 90 days before screening. \### Medical history or documented evidence of any of the following disorders 18. Prior bariatric-metabolic surgery or planned bariatric-metabolic surgery within 1 year; 19. Obesity secondary to underlying diseases or medications: e.g., hypercortisolism (Cushing's syndrome), obesity due to pituitary-hypothalamic injury, obesity following dose reduction/discontinuation of anti-obesity drugs, monogenic obesity, etc.; 20. Confirmed type 1 diabetes mellitus; 21. Prior severe hypoglycaemia or recurrent symptomatic hypoglycaemic episodes (≥ 2 events within 6 months before screening); 22. History of retinopathy; 23. Abnormal thyroid function (including TSH ≤ 0.1 mIU/L or ≥ 10 mIU/L) within 7 days before screening, or history of thyroid surgery; 24. Personal or family history of pancreatitis; 25. Personal or family history of medullary thyroid carcinoma; 26. Personal or family history of multiple endocrine neoplasia syndrome type 2; 27. History of malignant neoplasm or malignant tumour in remission; 28. History of moderate-to-severe depression; or history of severe psychiatric disorders including schizophrenia, bipolar disorder, etc.; 29. Prior suicidal ideation or suicidal behaviour; 30. Limb deformity or amputation precluding accurate measurement of height and body weight; 31. Post-procedural 12-lead ECG showing sinus heart rate \< 50 beats/min, second- or third-degree atrioventricular block, long-QT syndrome, or QTcF \> 450 ms (male), QTcF \> 470 ms (female); 32. Contraindications or known hypersensitivity to mazdutide. \### Exclusion by laboratory values at screening 33. Serum calcitonin ≥ 50 ng/L (pg/mL); 34. Fasting triglycerides ≥ 5.64 mmol/L (500 mg/dL); 35. Serum amylase or lipase \> 2.0 × upper limit of normal (ULN). \### Other criteria 36. Pregnant or lactating women; subjects (male or female) of child-bearing potential who plan pregnancy within 1 year or decline contraception throughout the study period and for 8 weeks after study completion; 37. Life expectancy \< 1 year due to malignancy, severe organ failure, or other conditions; 38. Any other conditions that, in the investigator's judgement, render the subject unsuitable for study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence of atrial arrhythmias at 12 months after a single ablation procedure without the use of any Class I/III antiarrhythmic drugs (AADs). | From enrollment to the end of treatment at 52 weeks | Recurrence of atrial arrhythmias (including AF, atrial flutter, and atrial tachycardia) recorded on a standard 12-lead surface ECG for ≥10 seconds, or on a 24-hour Holter monitor (including single-lead ECG patches) for \>30 seconds, at 12 months after a single ablation procedure (after a 3-month blanking period), without the use of any Class I/III antiarrhythmic drugs (AADs). |
| Composite serious adverse events (SAEs) occurring during the perioperative period and follow-up period. | From enrollment to the end of treatment at 52 weeks | 1. follow-up period, including cardiac tamponade/cardiac perforation, acute cerebrovascular events, acute coronary syndrome, pericarditis, acute kidney injury, third-degree atrioventricular block, serious bleeding events, atrial-esophageal fistula, pericardial-esophageal fistula, pulmonary vein stenosis, death, etc.; 2. Incidence of mazdutide-related adverse reactions, such as nausea/vomiting/diarrhea/abdominal pain, elevated serum calcitonin, elevated pancreatic enzymes, severe hypoglycemia, arrhythmia or conduction system disorders, severe liver function abnormality, severe renal function abnormality, thyroid C-cell hyperplasia or thyroid carcinoma, cholelithiasis, acute cholecystitis, cholecystectomy, severe hypersensitivity reactions, etc. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence of atrial arrhythmias at 12 months after a single ablation procedure with or without the use of any Class I/III antiarrhythmic drugs (AADs). | From enrollment to the end of treatment at 52 weeks | Recurrence of atrial arrhythmias (including AF, atrial flutter, and atrial tachycardia) at 12 months after a single ablation procedure (after a 3-month blanking period), with or without the use of Class I/III AADs; |
| Recurrence of AF at 12 months after a single ablation procedure with or without the use of any Class I/III antiarrhythmic drugs (AADs). | From enrollment to the end of treatment at 52 weeks | Recurrence of AF recorded on a standard 12-lead surface ECG for ≥10 seconds, or on a 24-hour Holter monitor (including single-lead ECG patches) for \>30 seconds, at 12 months after a single ablation procedure (after a 3-month blanking period), without the use of Class I/III AADs; |
| Recurrence of AT or AFL at 12 months after a single ablation procedure with or without the use of any Class I/III antiarrhythmic drugs (AADs). | From enrollment to the end of treatment at 52 weeks | Recurrence of atrial flutter or atrial tachycardia recorded on a standard 12-lead surface ECG for ≥10 seconds, or on a 24-hour Holter monitor (including single-lead ECG patches) for \>30 seconds, at 12 months after a single ablation procedure (after a 3-month blanking period), without the use of Class I/III AADs; |
| Recurrence of atrial arrhythmias after single or multiple ablations during the 12-month follow-up | From enrollment to the end of treatment at 52 weeks" | Recurrence of atrial arrhythmias (including AF, atrial flutter, and atrial tachycardia) after single or multiple ablations during the 12-month follow-up, with or without the use of Class I/III AADs; |
| AF burden | From enrollment to the end of treatment at 52 weeks | AF burden (% time) measured at the 12-month follow-up; |
| Body weight | From enrollment to the end of treatment at 52 weeks | Changes in body weight in kilograms from baseline to the 12-month follow-up; |
| Apnea-Hypopnea Index | From enrollment to the end of treatment at 52 weeks | Changes in Apnea-Hypopnea Index (AHI) from baseline to the 12-month follow-up; |
| Change in Atrial Fibrillation Effect on QualiTy-of-Life Questionnaire (AFEQT) Score From Baseline to 12 Months | From enrollment to the end of treatment at 52 weeks | The Atrial Fibrillation Effect on QualiTy-of-Life Questionnaire will be used to assess quality of life. The AFEQT total score ranges from 0 to 120, with higher scores indicating better quality of life. Changes from baseline to the 12-month (52-week) follow-up will be reported. |
| Cardiovascular-related hospitalizations | From enrollment to the end of treatment at 52 weeks | Incidence of cardiovascular-related hospitalizations during the 12-month follow-up; |
Countries
China
Contacts
CONTACTDeyong Long
CONTACTJin Shuyu Jin Shuyu
Outcome results
None listed