Empagliflozin for Acute Heart Failure

(DRIP-AHF-1 Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

Must be taking: Loop diuretics

Must not be taking: SGLT-2 inhibitors

Disqualifiers: Type 1 diabetes, Liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 5 days

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have used an SGLT-2 inhibitor or a combined SGLT-1 and SGLT-2 inhibitor in the last 48 hours. You also cannot start a new non-loop diuretic, except for an MRA (mineralocorticoid receptor antagonist).

Is empagliflozin safe for humans?

Empagliflozin, also known as Jardiance, is generally safe for humans and is well tolerated, with fewer serious adverse events compared to a placebo in patients with heart failure. However, patients should be monitored for potential side effects like fluid deficits. ^{1 2 3 4 5}

How does the drug empagliflozin differ from other treatments for acute heart failure?

Empagliflozin is unique because it is originally a diabetes medication that has been found to reduce the risk of cardiovascular death and hospitalization in heart failure patients, even those without diabetes. It works by inhibiting a protein that helps reabsorb glucose in the kidneys, which also leads to benefits like reduced fluid retention and blood pressure, making it effective for heart failure. ^{1 2 3 4 6}

What data supports the effectiveness of the drug empagliflozin for acute heart failure?

Research shows that empagliflozin helps reduce the risk of death and hospital visits for people with heart failure, even if they don't have diabetes. In a study, patients with acute heart failure who took empagliflozin experienced significant health benefits compared to those who did not take the drug. ^{1 2 3 4 7}

Who Is on the Research Team?

Thomas Mavrakanas, MD

Principal Investigator

Research Institute of the McGill University Health Center

Are You a Good Fit for This Trial?

This trial is for adults with acute heart failure and moderate to advanced chronic kidney disease who are not responding well to diuretics. They must have stable blood pressure, no severe liver disease, no history of type 1 diabetes or recent use of SGLT-2 inhibitors, and not be pregnant or breastfeeding.

Inclusion Criteria

My body didn't respond well to water pills, showing little urine output or weight loss.

I have severe heart failure with symptoms at rest and signs of fluid buildup.

Your blood pressure has been steady without needing certain medications for the past day.

Exclusion Criteria

I have been diagnosed with type 1 diabetes.

Criterion: Experiencing a type of diabetic ketoacidosis with normal blood sugar levels.

I have no GI surgeries or disorders affecting medication absorption.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

Treatment

Participants receive empagliflozin in addition to furosemide to assess diuretic effect

5 days

Daily monitoring (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Empagliflozin

Trial Overview The study tests if empagliflozin can boost the water-pill effect of furosemide in patients with heart failure who don't pee enough after taking diuretics. It's a single-group study where all participants get both drugs at McGill University Health Centre.

How Is the Trial Designed?

Group I: Patients with diuretic resistance Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

McGill University Health Centre/Research Institute of the McGill University Health Centre

Lead Sponsor

Trials

476

Recruited

170,000+

Published Research Related to This Trial

In the EMPEROR-Reduced study involving over 3700 participants with chronic heart failure and reduced ejection fraction, empagliflozin significantly reduced the risk of hospitalization for heart failure complications (13.2% vs. 18.3% for placebo) over an average of 16 months.

Empagliflozin also showed a lower incidence of serious kidney problems (1.6% vs. 3.1% for placebo), indicating its potential safety and efficacy in managing heart failure, although it was associated with a higher rate of genital tract infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug treatment with empagliflozin lowered risk for hospitalization in people with heart failure with reduced ejection fraction: plain language summary of the EMPEROR-Reduced study. Zannad, F., Macari, S.[2023]

Empagliflozin (Jardiance) is now approved for reducing the risk of cardiovascular death and hospitalization in adults with heart failure, even in those without diabetes, highlighting its expanded therapeutic use.

Healthcare providers, including nurses and nurse practitioners, should closely monitor patients for potential adverse effects, particularly fluid deficits, to ensure patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diabetes Drug Now Approved for Heart Failure. Aschenbrenner, DS.[2023]

Empagliflozin (EMPA) significantly reduced the induction of ventricular fibrillation (VF) in an ex-vivo model of ischemia-reperfusion, with only 16.7% of EMPA-treated hearts experiencing VF compared to 60% in control hearts.

EMPA improved cardiac contractility, as shown by a higher left ventricular developed pressure (LVDP) and enhanced calcium cycling, indicating its potential to protect heart function during ischemic events through mechanisms that do not involve sodium-glucose co-transporter-2 (SGLT2).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-arrhythmic and inotropic effects of empagliflozin following myocardial ischemia. Azam, MA., Chakraborty, P., Si, D., et al.[2021]

In a double-blind trial involving 530 patients hospitalized for acute heart failure, empagliflozin significantly improved clinical outcomes compared to placebo, demonstrating a 36% higher likelihood of achieving clinical benefit within 90 days.

Empagliflozin was well tolerated, with fewer serious adverse events reported in patients receiving the drug (32.3%) compared to those on placebo (43.6%), indicating its safety for use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Voors, AA., Angermann, CE., Teerlink, JR., et al.[2022]

In a study of 59 patients with type 2 diabetes and acute decompensated heart failure, empagliflozin as an add-on therapy significantly reduced NT-proBNP levels and improved decongestion compared to conventional glucose-lowering therapy.

Empagliflozin did not increase the risk of worsening renal function, indicating it is a safe option for managing heart failure in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Empagliflozin as an Add-On Therapy on Decongestion and Renal Function in Patients With Diabetes Hospitalized for Acute Decompensated Heart Failure: A Prospective Randomized Controlled Study. Tamaki, S., Yamada, T., Watanabe, T., et al.[2021]

In a study of 3730 patients with heart failure and reduced ejection fraction, empagliflozin significantly reduced the combined risk of death, hospitalization for heart failure, and urgent heart failure visits, showing benefits as early as 12 days after starting treatment.

Empagliflozin also led to fewer hospitalizations requiring intensive care and reduced the need for diuretic intensification, while improving patients' functional class, demonstrating its efficacy in managing worsening heart failure events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Empagliflozin on the Clinical Stability of Patients With Heart Failure and a Reduced Ejection Fraction: The EMPEROR-Reduced Trial. Packer, M., Anker, SD., Butler, J., et al.[2023]

Empagliflozin effectively lowers blood sugar levels in patients with type 2 diabetes by inhibiting glucose reabsorption in the kidneys, resulting in an average reduction of HbA1c by approximately 0.8% without causing hypoglycemia, except in those already on insulin or sulphonylureas.

In addition to improving glycemic control, empagliflozin promotes weight loss (about 2 kg) and lowers blood pressure (systolic by approximately 4 mm Hg), while also providing cardiovascular protection, as demonstrated in the EMPA-REG OUTCOME trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[EMPAGLIFLOZIN (JARDIANCE) :Nw SGLT2 COTRANSPORTER INHIBITOR FOR TREATING TYPE 2 DIABETES]. Scheen, AJ.[2022]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Drug treatment with empagliflozin lowered risk for hospitalization in people with heart failure with reduced ejection fraction: plain language summary of the EMPEROR-Reduced study. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Diabetes Drug Now Approved for Heart Failure. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Anti-arrhythmic and inotropic effects of empagliflozin following myocardial ischemia. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Effect of Empagliflozin as an Add-On Therapy on Decongestion and Renal Function in Patients With Diabetes Hospitalized for Acute Decompensated Heart Failure: A Prospective Randomized Controlled Study. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Effect of Empagliflozin on the Clinical Stability of Patients With Heart Failure and a Reduced Ejection Fraction: The EMPEROR-Reduced Trial. [2023]

7. Belgium pubmed.ncbi.nlm.nih.gov

[EMPAGLIFLOZIN (JARDIANCE) :Nw SGLT2 COTRANSPORTER INHIBITOR FOR TREATING TYPE 2 DIABETES]. [2022]