Empagliflozin in Heart Failure Patients With Reduced Ejection Fraction

Study Overview
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Brief Summary
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To assess the effect of Empagliflozin on cardiac biomarkers, cardiac function at rest and during stress, cardiac hemodynamics, renal function, metabolism, daily activity level and health-related quality of life in stable, symptomatic heart failure patients with reduced left ventricular ejection fraction. The primary hypothesis is that 3 months' treatment with Empagliflozin 10 mg a day will reduce the plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP).

Official Title
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Empagliflozin in Heart Failure Patients With Reduced Ejection Fraction: A Randomized Clinical Trial (Empire HF)

Conditions
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Heart Failure With Reduced Ejection Fraction

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Optimal Heart Failure Therapy in accordance with European and National Guidelines LVEF ≤ 0.40 eGFR > 30 ml/min/1.73 m2 BMI < 45 kg/m2 NYHA class I-III Age > 18 years If T2D - optimal treatment in accordance with European and National Guidelines If T2D - stable doses of antiglycemic treatment for 30 days If T2D - HbA1C 6.5-10% Exclusion Criteria: CRT-D/-P implanted < 90 days Uncorrected severe valvular disease Non-compliance Use of metalozone NYHA IV Age > 85 years Dementia Admission for HF < 30 days Admission for hypoglycemia < 12 month Known sustained VT Symptomatic hypotension and systolic BP < 95 mmHg Unable to perform an exercise test Immobilization Pregnancy Participation in other medical trials Previous intolerance of Empagliflozin or excipients

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Empagliflozin 10 mg<br> | Drug: Empagliflozin 10 MG<br>* Capsule, once a day for 90 days<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Capsule, once a day for 90 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Between-group difference in the change of plasma concentrations of NT-proBNP |  | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Between-group difference in the change in daily activity level measured by patient-worn accelerometers as change in the amount of daily average accelerometer units |  | 90 days | 
| Between-group difference in the change in body composition assessed by DXA scan |  | 90 days | 
| Between-group difference in the change of estimated extracellular volume assessed by Cr-51 EDTA clearance |  | 90 days | 
| Between-group difference in the change of estimated plasma volume assessed by hematocrit and hemoglobin |  | 90 days | 
| Between-group difference in the change of glucose metabolism assessed by oral glucose tolerance test |  | 90 days | 
| Between-group difference in the change of ketone supply to the heart assessed by blood ketones |  | 90 days | 
| Between-group difference in the change of renal function assessed by Cr-51 EDTA clearance |  | 90 days | 
| Between-group difference in the change of uric acid |  | 90 days | 
| Between-group difference in the change of urine albumin/creatinine ratio |  | 90 days | 
| Between-group difference in the change of cardiac biomarkers assessed by plasma concentrations of MR-proADM and hs-cTnI |  | 90 days | 
| Between-group difference in the change of cardiac systolic and diastolic function including left ventricular global longitudinal strain and left ventricular ejection fraction assessed by transthoracic echocardiography at rest and during stress |  | 90 days | 
| Between-group difference in the change of cardiac hemodynamics during rest and sub-maximal exercise assessed by right heart catheterization including pulmonary capillary wedge pressure to cardiac index ratio |  | 90 days | 
| Between-group difference in the change of cardiac hemodynamics during rest and sub-maximal exercise assessed by right heart catheterization including left ventricular contractile reserve |  | 90 days | 
| Between-group difference in the change of health-related quality of life assessed by the questionnaire KCCQ |  | 90 days | 
| Between-group difference in the change of health-related quality of life assessed by the questionnaire EQ-5D-5L |  | 90 days |