DUTCH Weight Control in Atrial Fibrillation Study (DUTCH-WAIST)

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

Quantify the effect of an innovative weight loss management on rhythm control.

Study Overview

• Status: Not yet recruiting
• Conditions: Obesity; Atrial Fibrillation; Weight Loss
• Intervention / Treatment: Drug: Semaglutide 3.2 MG/ML; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 280
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Leonard Voorhout, MSc; Phone Number: +31650818296; Email: lvoorhout@rijnstate.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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 isolationWhen 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
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
Change in AF related symptoms measured by the modified EHRA classification between the index visit and at 12 months after the index visit.	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	week 0 and 52
Change in quality of life measured by the EQ-5D-5L between the index visit and at 12 months after the index visit.	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	week 0 and 52

Collaborators and Investigators

• Sponsor: Rijnstate Hospital
• Investigators: Principal Investigator: Ron Pisters, dr., Rijnstate Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: December 14, 2023
• First Submitted That Met QC Criteria: December 14, 2023
• First Posted (Actual): December 28, 2023

Study Record Updates

• Last Update Posted (Estimated): January 8, 2024
• Last Update Submitted That Met QC Criteria: January 4, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Body Weight Changes; Atrial Fibrillation; Weight Loss; Body Weight
• Other Study ID Numbers: U1111-1275-9989

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No