DUTCH Weight Control in Atrial Fibrillation Study

Study Overview
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Brief Summary
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Quantify the effect of an innovative weight loss management on rhythm control.

Detailed Description
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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.

Official Title
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DUTCH Weight Control in Atrial Fibrillation Study, a Multi-center, Double-blind, Randomized, Parallel Group, Placebo-controlled Trial

Conditions
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Atrial Fibrillation, Obesity, Weight Loss

Intervention / Treatment
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* Drug: Semaglutide 3.2 MG/ML
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention<br>Semaglutide injections + combined lifestyle intervention | Drug: Semaglutide 3.2 MG/ML<br>* Intervention arm receives semaglutide in addition to combined lifestyle intervention<br>|
| Placebo Comparator: Placebo<br>Placebo Semaglutide injections + combined lifestyle intervention | Drug: Placebo<br>* Control arm receives placebo in addition to combined lifestyle intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | At 1 year follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in AF related symptoms measured by the modified EHRA score between the index visit and at 12 months after the index visit. |  | week 0 and 52 | 
| Change in quality of life measured by the EQ-5D between the index visit and at 12 months after the index visit. |  | week 0 and 52 | 
| Number of hospitalizations because of an AF recurrence. |  | week 0-52 | 
| Number of unscheduled hospital visits because of adverse events of AAD. |  | week 0-52 | 
| Number of scheduled electrical cardioversions. |  | week 0-52 | 
| Number of unscheduled electrical cardioversions. |  | week 0-52 | 
| Number of intravenous chemical cardioversions (using Vaughan-Williams class I drugs). |  | week 0-52 | 
| Total number of unscheduled cardioverions. |  | week 0-52 | 
| Change in waist circumference, measured in cm |  | week 0 and 52 | 
| Change in weight, measured in % and kg |  | week 0 and 52 | 
| Change in BMI, measured in kg/m2 |  | week 0 and 52 |