Empagliflozin and Atrial Fibrillation Treatment

Study Overview
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Brief Summary
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The primary purpose of this trial is to evaluate the impact of empagliflozin, as compared with placebo, in patients with diabetes mellitus or overweight, heart failure and atrial fibrillation.

Detailed Description
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A 24-month randomized, single-blind, placebo-controlled trial to investigate the efficacy of empagliflozin to reduce atrial fibrillation burden in patients with diabetes mellitus or overweight, heart failure and atrial fibrillation in which a rhythm control strategy is indicated.

Official Title
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Efficacy of Empagliflozin in Patients With Heart Failure and Atrial Fibrillation

Conditions
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Atrial Fibrillation, Heart Failure, Obesity, Diabetes Mellitus

Intervention / Treatment
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* Drug: Empagliflozin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-80 years Diabetes mellitus or Body Mass Index over 25 Kg/m2 Heart failure New York Heart Association (NYHA) Functional Classification: II or III Documented atrial fibrillation Understands the nature of the study, treatment procedure and provides written informed consent Willing to comply with specified pre-, post- and follow-up testing, evaluations and requirements Expected to remain available for at least 24 months after enrollment Exclusion Criteria: Permanent atrial fibrillation Current use or prior use of a sodium-glucose co-transporter (SGLT) 2 inhibitor or combined inhibitor of SGLT-1 and SGLT-2 (all the other antidiabetic drugs are permitted performing an accurate glycemic control) Known allergy or hypersensitivity to any SGLT-2 inhibitors History of ketoacidosis Need or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial New York Heart Association (NYHA) Functional Classification: I or IV Unstable angina Presence of any disease that is likely to shorten life expectancy to < 1 year Any cardiac surgery within three months prior to enrolment Awaiting cardiac transplantation or other cardiac surgery within the next year Myocardial infarction within 60 days prior to enrolment Contraindications to oral anticoagulation Active systemic infection or sepsis Left atrial thrombus (e.g., transesophageal echocardiography, computed tomography and intracardiac echocardiography) History of a documented thromboembolic event such as stroke or transient ischemic neurological attack in the three months prior to enrollment Currently enrolled in another trial that has not completed the required follow-up period and would conflict with this study Chronic liver diseases Chronic kidney disease (creatinine clearance < 45 ml/min) Pregnant or breast-feeding mothers Any other clinical condition that might jeopardize patient safety during participation in this trial or prevent the subject from adhering to the trial protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Empagliflozin<br>Empagliflozin 10 mg oral tablet, once daily, for 24 months | Drug: Empagliflozin<br>* Empagliflozin 10 mg oral tablet, once daily, for 24 months<br>* Other names: Empagliflozin 10 mg oral tablet;|
| Placebo Comparator: Placebo<br>Empagliflozin matching placebo oral tablet, once daily for 24 months | Other: Placebo<br>* Empagliflozin matching placebo, once daily, for 24 months<br>* Other names: Placebo oral tablet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maintenance of sinus rhythm after the blanking period | To compare the proportion of patients with sinus rhythm from 90 days after baseline to end of study period | From 90 days after baseline to 24-months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of major adverse cardiovascular events | To compare the incidence at the end of study period of major adverse cardiovascular events (death, non-fatal myocardial infarction, acute cerebrovascular events) | Baseline through 24-months | 
| Hospitalizations for cardiovascular events | To compare the incidence at the end of study period of hospitalizations for cardiovascular events | Baseline through 24-months | 
| Safety endpoint: Incidence of adverse events | To estimate the incidence of adverse events | Baseline through 24-months |