The Metabolic Effects of Empagliflozin in Patients With High Risk of Heart Failure

Study Overview
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Brief Summary
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The aim of this trial is to assess the effect of Empagliflozin on lipid and glucose metabolism as well as volume homeostasis and renal function in elderly and obese patients with increased risk of developing heart failure. No history of established heart failure or diabetes is allowed. The primary hypotheses are that 6 months treatment with Empagliflozin 10 mg a day will: 1) decrease epicardial adipose tissue volume, and 2) reduce estimated extracellular volume compared with placebo.

Detailed Description
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The Empire Prevent: Metabolic is a part of the Empire Prevent Trial Program, which also comprises the Empire Prevent: Cardiac. The Empire Prevent: Metabolic is designed to enroll at least 120 patients.

Official Title
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Empagliflozin to Elderly and Obese Patients With Cardiovascular Disease (Empire Prevent: Metabolic): A Randomized Controlled Trial

Conditions
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Obesity, Heart Failure

Intervention / Treatment
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* Drug: Empagliflozin 10 MG
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index >28kg/m2 Age 60-84 years Established risk factor for developing heart failure, defined as at least one of the following: hypertension ischemic heart disease stroke/transient cerebral ischemia chronic kidney disease (eGFR 30-45ml/min/1.73m2) Exclusion Criteria: Diabetes mellitus type 1 or 2 (no medical history, no antidiabetic treatment) Heart failure with reduced ejection fraction (LVEF <40%) Inability to perform exercise test Dementia Severe non-compliance Substance abuse Severe chronic obstructive pulmonary disease (FEV1<50% expected value) Permanent atrial fibrillation GFR <30 ml/min/1,73m2 Severe peripheral artery disease Cancer treatment within one year beside prostate cancer and basal cell carcinoma Severe aortic or mitral valve disease Pregnancy or breastfeeding Acute hospital admission within 30 days Participation in other pharmacological study

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 84 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active drug (Empagliflozin)<br>Empagliflozin 10 mg, 1 capsule per day | Drug: Empagliflozin 10 MG<br>* Patients are randomized 1:1 to receive either Empagliflozin or matching placebo for 180 days<br>|
| Placebo Comparator: Inactive drug (placebo)<br>Placebo, 1 capsule per day | Drug: Placebo<br>* Placebo matches the active drug in appearance, odor and labelling.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Epicardial adipose tissue (EAT) | Between-group difference in the change of EAT volume assessed by cardiac magnetic resonance imaging (MRI) | 180 days | 
| Estimated extracellular volume (eECV) | Between-group difference in the change of eECV assessed by 99mTc-DTPA clearance (technetium-99mTc-diethylenetriaminepentaacetic acid) | 180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body composition | Between-group difference in the change in body composition assessed by dual energy x-ray absorptiometry (DXA) scan | 180 days | 
| Plasma volume | Between-group difference in the change of estimated plasma volume assessed by hematocrit and hemoglobin | 180 days | 
| Glucose tolerance | Between-group difference in the change of glucose metabolism assessed by oral glucose tolerance test | 180 days | 
| Kidney function (measured) | Between-group difference in the change of glomerular filtration rate assessed by 99mTc-DTPA clearance | 180 days | 
| Kidney function (estimated) | Between-group difference in the change of estimated glomerular filtration rate (eGFR) based on the chronic kidney disease epidemiology collaboration (CKD-EPI) estimation | 180 days | 
| Uric acid | Between-group difference in the change of uric acid | 180 days | 
| Urine albumin/creatinine ratio | Between-group difference in the change of urine albumin/creatinine ratio | 180 days | 
| Right ventricle | Between-group difference in the change of right ventricular systolic and diastolic dimensions assessed by cardiac MRI | 180 days | 
| Pericardial fat mass | Between-group difference in the change of pericardial fat mass assessed by cardiac MRI | 180 days | 
| Ketone bodies | Between-group difference in the change of ketone supply to the heart assessed by blood ketones | 180 days | 
| Erythropoietin | Between-group difference in the change of erythropoietin | 180 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal function, Glucose intolerance, Lipid metabolism