Clinical trial NCT05305495: Empagliflozin in Acute Heart Failure
Official title: Empagliflozin for Patients With Acutely Decompensated Congestive Heart Failure, Diuretic Resistance, and Moderate to Advanced Chronic Kidney Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Acute Heart Failure
Chronic Kidney Diseases
Keywords: Empagliflozin
Acute Heart Failure
Chronic kidney disease
Diuretic resistance
Furosemide
Lead sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
Sponsor class: OTHER
First posted: 2022-03-31
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective, interventional, single arm, cohort study
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Diuretic effect of empagliflozin in association with furosemide
timeFrame: Day 1
Secondary outcomes:
measure: Fractional excretion of sodium in the urine
timeFrame: Day 1
measure: Total urine sodium output
timeFrame: Day 1-5
measure: Changes in volume status
timeFrame: Day 1-5
measure: Incidence of AKI
timeFrame: Day 1-5
measure: Electrolyte abnormalities - Sodium
timeFrame: Day 1-5
measure: Electrolyte abnormalities - Potassium
timeFrame: Day 1-5
measure: Electrolyte abnormalities - Magnesium
timeFrame: Day 1-5
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Research Institute of the McGill University Health Center
state: Quebec
Study officials:
affiliation: Research Institute of the McGill University Health Center
name: Thomas Mavrakanas, MD
role: PRINCIPAL_INVESTIGATOR
References: