Empagliflozin in Acute Heart Failure (DRIP-AHF-1)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Kidney Diseases; Acute Heart Failure
• Intervention / Treatment: Drug: Empagliflozin 25 MG

• Study Type: Interventional
• Enrollment (Anticipated): 25
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada
      • Recruiting
      • Research Institute of the McGill University Health Center
      • Contact: Pedro Marques; Phone Number: 5149341934; Email: pedro.marques@mail.mcgill.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Patients with diuretic resistance

Drug: Empagliflozin 25 MG; 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.; Other Names: Jardiance (DIN: 02443945)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Investigators: Principal Investigator: Thomas Mavrakanas, MD, Research Institute of the McGill University Health Center

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2022
• Primary Completion (Anticipated): August 1, 2024
• Study Completion (Anticipated): July 1, 2025

Study Registration Dates

• First Submitted: March 4, 2022
• First Submitted That Met QC Criteria: March 29, 2022
• First Posted (Actual): March 31, 2022

Study Record Updates

• Last Update Posted (Actual): January 4, 2023
• Last Update Submitted That Met QC Criteria: January 3, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Empagliflozin; Chronic kidney disease; Acute Heart Failure; Furosemide; Diuretic resistance
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Urologic Diseases; Renal Insufficiency; Heart Failure; Kidney Diseases; Renal Insufficiency, Chronic; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin
• Other Study ID Numbers: 2022-8411

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No