Danish Trial of Weight Loss to Reduce Atrial Fibrillation Progression

What this study is testing ClinicalTrials.gov NCT07816744 ↗

Description as written by the study sponsor.

Obesity is an important risk factor for the development and progression of atrial fibrillation. Sustainable weight loss likely reduces the burden of atrial fibrillation, which has yet to be proven in adequately sized randomised trials. In a national, multicentre randomised trial we will test, whether a sustainable weight loss of more than 10% reduces atrial fibrillation progression and burden in patients with symptomatic paroxysmal or early persistent atrial fibrillation and a body mass index ≥27 kg/m2. A total of 480 patients will be randomised in a 1:1 fashion to either a comprehensive weight loss programme of behavioural support, meal replacement and/or pharmacotherapy with a glucagon-like peptide-1 receptor agonist on top of standard care aiming at more than 10% weight loss or standard care alone. Standard care will include guideline-directed anticoagulant therapy for stroke prevention, rate and/or rhythm control treatment, and management of risk factors and underlying cardiovascular conditions. Patients in the standard care group will receive information on weight management, but no active treatment for weight loss. Patients will be enrolled during a period of two and a half years and will be followed for one year with an equal number of study visits in both study arms. All patients will receive a 14-day continuous electrocardiographic monitoring at baseline, four, eight, and 12 months. The study endpoints will be assessed after a 4-months blanking period from month four to 12 to allow for weight loss. The primary endpoint will be a hierarchical composite of atrial fibrillation progression, symptom burden, and treatment escalation. Secondary endpoints will be a change in weight, total atrial fibrillation burden, quality of life, and metabolic and cardiovascular biomarkers from baseline to 12 months. Safety endpoints will be adverse events related to treatment with glucagon-like peptide-1 receptor agonists and weight loss. Endpoint adjudication will be blinded.

Treatments tested

• Structured weight loss program including behavioral support and optional meal re-placement or pharmacotherapy with Glucagon-like peptide-1 receptor agonists (GLP1-RA) Other

  Weight loss period (0-16 weeks): Behavioural support (first step): Dietician-guided lifestyle vhanges through virtual meeting, frequency by patient's choice; energy intake 1500 kcal/day; \<30% carbohydrates, \>=60 g protein/day, adeqaute fiber, 2-2.5 L/day non-caloric fluids. Escalation strategy (second step): Meal replacement: available free of charge Pharmacotherapy: Semaglutide once weekly subcutaneous injection Target weight loss \>10%; aiming for a 1% weight loss per week during the weight loss period. Weight loss maintenance period (17-52 weeks): Maintenance of \>10% weigth loss Further lifestyle changes, meal replacement, or dose adjustment of weight loss medication

• Standard Care (in control arm) Other

  Guideline-directed cardiovascular risk factor management, including medical treatment and lifestyle counseling.