Empagliflozin in Acute Heart Failure

Study Overview
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Brief Summary
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The objective is to study in a prospective, interventional, single arm, cohort study the potential synergistic diuretic effect of empagliflozin, in addition to furosemide, in hypervolemic patients admitted with acutely decompensated heart failure and diuretic resistance at the McGill University Health Centre (MUHC). The investigators hypothesize that the sodium-glucose cotransporter-2 (SGLT-2) inhibitor empagliflozin will enhance the diuretic effect of furosemide in patients with acutely decompensated heart failure, moderate to advanced chronic kidney disease, and underlying diuretic resistance, as identified by the three-hour urine output post diuretic administration on the first day of the study, compared with furosemide alone.

Official Title
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Empagliflozin for Patients With Acutely Decompensated Congestive Heart Failure, Diuretic Resistance, and Moderate to Advanced Chronic Kidney Disease

Conditions
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Acute Heart Failure, Chronic Kidney Diseases

Intervention / Treatment
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* Drug: Empagliflozin 25 MG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (all have to apply) : moderate to advanced CKD, defined as an eGFR <45 ml/min/1.73m2; The average creatinine values over the last 12 months will be used to calculate baseline eGFR. acutely decompensated heart failure, defined as dyspnea at rest or with minimal physical activity, associated with at least one clinical sign of congestion and at least one objective measure of heart failure (pulmonary-capillary wedge pressure >20 mm Hg or evidence of pulmonary congestion on chest radiography or brain natriuretic peptide (BNP) level ≥400 pg/ml or N-terminal pro-BNP level ≥1000 pg/ml); evidence of inadequate response to loop diuretics, defined as a urine output < 1000 ml/24h or a weight loss < 1kg /24h. For patients who have not received loop diuretics, a furosemide stress test can be conducted. stable hemodynamics, defined as systolic blood pressure >90 mmHg and/or mean arterial pressure >65 mmHg in the absence of intravenous norepinephrine or epinephrine in the last 24 hours. Exclusion Criteria: new use of a non-loop diuretic other than an MRA history of type 1 diabetes mellitus euglycemic diabetic ketoacidosis liver disease defined by serum levels of transaminases or alkaline phosphatase more than three times the upper limit of normal at screening known hypersensitivity to SGLT-2 inhibitors use within the last 48 h of an SGLT-2 inhibitor or a combined SGLT-1 and SGLT-2 inhibitor maintenance dialysis or need for emergent renal replacement therapy gastrointestinal surgery or gastrointestinal disorder that could interfere with trial medication absorption recurrent severe genital or urinary tract infection pregnancy or breastfeeding any other clinical condition that would jeopardize patient safety while participating in this trial Patients with an acute rise in creatinine levels (acute cardiorenal syndrome) upon presentation will not be excluded.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Interventional Model Description: Prospective, interventional, single arm, cohort study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with diuretic resistance<br> | Drug: Empagliflozin 25 MG<br>* Patients who fulfill the inclusion criteria will receive an intravenous dose of 1.0-1.5 mg/kg of furosemide (≤120 mg) and urine output will be monitored for three hours. Those with a urine output < 300 ml in the first two hours post furosemide administration will receive a single oral dose of 25 mg of empagliflozin. Two hours after taking empagliflozin, patients will receive a second intravenous dose of 1.0-1.5 mg/kg of furosemide with another timed urine collection at three hours. Empagliflozin will then be continued daily for five days or until hospital discharge, unless the treating physician considers this not to be clinically appropriate.<br>* Other names: Jardiance (DIN: 02443945);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diuretic effect of empagliflozin in association with furosemide | Three-hour urine output post empagliflozin-furosemide administration, compared with furosemide alone | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fractional excretion of sodium in the urine | FeNa (%) | Day 1 | 
| Total urine sodium output | Urine sodium per 24h | Day 1-5 | 
| Changes in volume status | Net fluid balance | Day 1-5 | 
| Incidence of AKI | Using the conventional KDIGO criteria | Day 1-5 | 
| Electrolyte abnormalities - Sodium | Concentration of sodium | Day 1-5 | 
| Electrolyte abnormalities - Potassium | Concentration of potassium | Day 1-5 | 
| Electrolyte abnormalities - Magnesium | Concentration of magnesium | Day 1-5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Empagliflozin, Acute Heart Failure, Chronic kidney disease, Diuretic resistance, Furosemide