Clinical trial NCT06184633: DUTCH Weight Control in Atrial Fibrillation Study
Official title: DUTCH Weight Control in Atrial Fibrillation Study, a Multi-center, Double-blind, Randomized, Parallel Group, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Atrial Fibrillation
Obesity
Weight Loss
Lead sponsor: Rijnstate Hospital
Sponsor class: OTHER
First posted: 2023-12-28
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: At 1 year follow-up
Secondary outcomes:
measure: Change in AF related symptoms measured by the modified EHRA classification between the index visit and at 12 months after the index visit.
timeFrame: week 0 and 52
measure: Change in quality of life measured by the EQ-5D-5L between the index visit and at 12 months after the index visit.
timeFrame: week 0 and 52
measure: Number of hospitalizations because of an AF recurrence.
timeFrame: week 0-52
measure: Number of unscheduled hospital visits because of adverse events of AAD.
timeFrame: week 0-52
measure: Number of scheduled electrical cardioversions.
timeFrame: week 0-52
measure: Number of unscheduled electrical cardioversions.
timeFrame: week 0-52
measure: Number of intravenous chemical cardioversions (using Vaughan-Williams class I drugs).
timeFrame: week 0-52
measure: Total number of unscheduled cardioverions.
timeFrame: week 0-52
measure: Change in waist circumference, measured in cm
timeFrame: week 0 and 52
measure: Change in weight, measured in % and kg
timeFrame: week 0 and 52
measure: Change in BMI, measured in kg/m2
timeFrame: week 0 and 52
Other outcomes:
Locations:
city: Arnhem
country: Netherlands
facility: Rijnstate Hospital
state: Gelderland
Study officials:
affiliation: Rijnstate Hospital
name: Ron Pisters, dr.
role: PRINCIPAL_INVESTIGATOR
References: