Semaglutide for the Reduction of Arrhythmia Burden in Overweight AF Patients

• Status: Not yet recruiting
• Trial end date: 2024-11-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this pilot study is to assess the feasibility of a double-blind, randomized placebo-controlled trial of semaglutide 2.4 mg subcutaneously once weekly on top of standard care compared to standard care alone.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Axel Brandes
• Collaborators: Herlev and Gentofte Hospital; Hillerod Hospital, Denmark; Hospital of South West Jutland; Svendborg Hospital

Criteria

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