Atrial Fibrillation, Obesity, Weight Loss
Conditions
Brief summary
Quantify the effect of an innovative weight loss management on rhythm control.
Detailed 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.
Interventions
DRUGSemaglutide 3.2 MG/ML
Intervention arm receives semaglutide in addition to combined lifestyle intervention
DRUGPlacebo
Control arm receives placebo in addition to combined lifestyle intervention
Sponsors
Rijnstate Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | At 1 year follow-up | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in quality of life measured by the EQ-5D-5L between the index visit and at 12 months after the index visit. | week 0 and 52 | Descriptive system for health-related quality of life states in adults, consisting of five dimensions (Mobility, Self-care, Usual activities, Pain & discomfort, Anxiety & depression), each of which has five severity levels that are described by statements appropriate to that dimension. LEVEL 1: indicating no problem LEVEL 2: indicating slight problems LEVEL 3: indicating moderate problems LEVEL 4: indicating severe problems LEVEL 5: indicating unable to/extreme problems |
| 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 | — |
| Change in AF related symptoms measured by the modified EHRA classification between the index visit and at 12 months after the index visit. | week 0 and 52 | EHRA: European Heart Rythm Association 1= no symptoms 2a= mild symptoms; Normal dialy activity not affected, symptoms not troublesome to patient 2b= moderate symptoms; Normal daily activity not affected but patient troubled by symptoms 3= severe symptoms; Normal daily activity affected 4= disabling symptoms; Normal daily activity discontinued |
| 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 | — |
| Number of intravenous chemical cardioversions (using Vaughan-Williams class I drugs). | week 0-52 | — |
Countries
Netherlands
Contacts
Primary ContactLeonard Voorhout, MSc
Outcome results
None listed