Semaglutide for the Reduction of Arrhythmia Burden in Overweight AF Patients (SOCRATES-AF)

This is an interventional treatment trial for Atrial Fibrillation focused on measuring Atrial fibrillation, Overweight, Obesity, Semaglutide, Glucagon-like peptide-1 (GLP-1) receptor agonist, Implantable cardiac monitor Read More

Inclusion Criteria:

• Signed informed consent before any study-related activity
• ≥ 18 years of age at the time of signing informed consent
• Body mass index (BMI) ≥ 30 kg/m2
• Body mass index (BMI) ≥ 27 kg/m2 and at least 1 concomitant cardiometabolic risk factor (hypertension, dyslipidemia, or obstructive sleep apnea)
• Symptomatic paroxysmal or early persistent atrial fibrillation (Paroxysmal AF: Self- terminating, in most cases within 48 hours up to 7 days. AF episodes that are cardioverted within 7 days with a documented 12 lead ECG showing sinus rhythm within the last 12 months; early persistent AF: AF episodes lasting longer than 7 days, including episodes that are terminated by cardioversion, either with drugs or by direct current cardioversion, after 7 days or more. Early persistent AF in this trial is defined as persistent AF with first-time electrical cardioversion (ECV) or a maximum of 1 previous ECVs.)

Exclusion Criteria:

• General exclusion criteria

  • Age ≥75 years
  • History of type 1 or 2 diabetes (history of gestational diabetes is allowed)
  • Known or suspected hypersensitivity to study medication or related products
  • Treatment with GLP-1 receptor agonists within the last 3 months before randomisation
  • Treatment with dipeptidyl peptidase-4 (DPP-4) inhibitors
  • Alcohol/drug abuse
  • Pregnant or breastfeeding women
  • Fertile women not using chemical (tablet/pill, depot injection of progesterone, sub- dermal gestagen implantation, hormonal vaginal ring or transdermal hormonal patch) or mechanical (spirals) contraceptives
  • Active malignancy, unless in complete remission for ≥5 years
  • Family or personal history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma (FMTC)
  • Personal history of non-familial medullary thyroid carcinoma
  • Inflammatory bowel diseases
  • Acute or chronic pancreatitis
  • Obesity induced by other endocrinologic disorders (e.g. Cushing's Syndrome)
  • Current history of treatment with medications that may cause significant weight gain, within the last 3 months before screening, including systemic corticosteroids (except for a short course of treatment, i.e. 7-10 days), tri-cyclic antidepressants, atypical antipsychotic and mood stabilizers (e.g. imipramine, amitriptyline, mirtazapine, paroxetine, phenelzine, chlorpromazine, thioridazine, clozapine, olanzapine, valproic acid and its derivatives, and lithium)
  • Diet attempts using herbal supplements or over-the-counter medications within 3 months before screening
  • Current participation (or within the last 3 months) in an organised weight reduction programme or currently using or used within 3 months before screening: pramlintide, sibutramine, orlistat, zonisamide, topiramate, phentermine (either by prescription or as part of a clinical trial)
  • Severe chronic obstructive pulmonary disease
  • Uncontrolled treated/untreated hypertension (systolic >180 mmHg and/or diastolic >105 mmHg)
  • Previous or planned surgical treatment for obesity
  • Life expectancy <2.5 years
  • Other concomitant disease or treatment that according to the investigator's assessment makes the subject unsuitable for study participation
  • Participation in any other clinical intervention trial
  • Previous participation in the SOCRATES-AF pilot study
  • Inability to sign informed consent

• Exclusion criteria related to a cardiac condition

  • Previous or planned AF ablation
  • Previous use of continuous prophylactic class I or III antiarrhythmic drugs
  • Long-standing persistent or permanent AF
  • Overall clinical history of persistent AF ≥5 years
  • ECG suggestive of malignant ventricular arrhythmia
  • Prolonged corrected QT-interval (>500 ms), unless caused by bundle branch block
  • Myocardial infarction (MI) within the last 3 months before screening
  • Coronary revascularization within the last 3 months before screening
  • Planned coronary revascularisation
  • Cardiac surgery within the last 12 months before screening
  • Obstructive hypertrophic cardiomyopathy
  • Clinically significant valvular heart disease
  • Left ventricular (LV) dysfunction (HFrEF with left ventricular ejection fraction (LVEF) <45%) unless elicited by AF
  • Hospitalization due to decompensated heart disease within 30 days prior to randomization
  • Congestive heart failure (NYHA class IV)
  • Current myocardial or pericardial infection
  • Permanent pacemaker (PM) in use or implantable cardioverter defibrillator (ICD)
  • Patient cannot be prescribed non-vitamin K oral anticoagulant (NOAC)
  • perform physical exercise for medical or personal reasons

• Exclusion criteria based on laboratory abnormalities

  • Liver disease with increased plasma alanine aminotransferase (ALAT) levels of more than three times the upper limit of normal
  • Renal dysfunction (eGFR <30 ml/min), dialysis or kidney transplant
  • Clinically manifest thyroid dysfunction requiring therapy. After successful treatment of thyroid dysfunction, subjects may be enrolled, when thyroid function is controlled.
  • HbA1c >6.5% measured at screening