Overview
Quantify the effect of an innovative weight loss management on rhythm control.
Description
Rationale: Weight reduction promotes reversed atrial remodeling in obese AF patients.
Objective: Quantify the effect of an innovative weight loss management on rhythm control.
Study design: Multi-center, double-blind, randomized, parallel group, placebo-controlled trial of semaglutide 2.4 mg versus placebo.
Study population: Adults with obesity and new onset persistent AF scheduled for electrical cardioversion.
Intervention: semaglutide 2.4 mg subcutaneous (s.c.) once weekly (index) compared to placebo (control), at the background of standard obesity treatment (combined lifestyle intervention) and cardiology follow-up management in both arms.
Main study parameters/endpoints: The primary efficacy clinical endpoint of the trial is assessed at 12 months by a 7 point scale. Only the worst clinical outcome will be retained as the primary efficacy outcome. The 7 mutually exclusive outcomes hierarchically ranked from worst to best are:
- Arrhythmic death while using anti-arrhythmic drugs (Vaughn-Williams class I or III)*
- AF despite pulmonary vein isolation
- AF despite current use of anti-arrhythmic drugs (Vaughn-Williams class I or III)
- AF without a pulmonary vein isolation and without the current use of anti-arrhythmic drugs (Vaughn-Williams class I or III)
- Sinus rhythm on the 12-lead ECG with the use of a pulmonary vein isolation
- Sinus rhythm on the 12-lead ECG with current use of anti-arrhythmic drugs (Vaughn-Williams class I or III)
- Sinus rhythm on the 12-lead ECG without the current use of anti-arrhythmic drugs (Vaughn-Williams class I or III) and without a pulmonary vein isolation
- When LTFU or death other than anti-arrhythmic death, last known rhythm will be used.
Eligibility
Inclusion Criteria:
- Symptomatic, first detected (at maximum 6 months prior to enrollment) persistent AF -
- Age ≥ 18
- Obesity, as defined as:
- BMI ≥ 30 kg/m2, or
- BMI ≥27 kg/m2 with the presence of at least one weight related comorbidity (treated or untreated, e.g. hypertension, dyslipidaemia, obstructive sleep apnea, cardiovascular disease)
- Scheduled ECV
- Written informed consent
Exclusion Criteria:
- Permanent AF
- Secondary AF, i.e. due to thyrotoxicosis, infection (e.g. pneumonia) or post-(cardiothoracic) surgery
- Current or previous treatment with amiodaron
- HbA1c ≥ 48 mmol/L, <3 months prior to randomization
- History of diabetes mellitus type 1 or 2
- Prior bariatric surgery
- Use of other anti-obesity medication, <3 months prior to enrollment
- Contra-indication for, or prior use of a GLP1-receptor agonist
- History of chronic pancreatitis or acute pancreatitis <6 months
- Acute coronary syndrome <6 months
- Severe (grade III) valvular disease
- eGFR <30 mL/min/1.73m2
- Heart failure NYHA class III-IV
- Participation in another investigational drug or device study in the past 30 days (registry enrollment is allowed)
- Any condition or therapy, which would make the participant unsuitable for the study (e.g. vulnerable, non-compliance) or life-expectancy <12 months, as judged by the treating physician.
- Female who is pregnant, breastfeeding, intends to become pregnant, or is of child-bearing potential and not using a highly effective contraceptive method.