SGLT2 Inhibitors for Heart Failure With LVADs

Overseen By Gene Kim, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Chicago

Disqualifiers: Type 1 diabetes, 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: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how SGLT2 inhibitors, a type of medication, can assist people with heart failure who use left ventricular assist devices (LVADs), which are mechanical heart pumps. The researchers aim to determine if these medications can enhance heart health and overall well-being. Participants will either take the medication for six months or continue their regular heart care without it. The trial seeks individuals with an LVAD who have not yet tried SGLT2 inhibitors. As a Phase 4 trial, this research focuses on an FDA-approved treatment to understand its benefits for more patients, offering participants a chance to contribute to valuable insights.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What is the safety track record for SGLT2 inhibitors?

Research has shown that SGLT2 inhibitors are generally safe for people with heart failure who have LVADs (devices that help the heart pump blood). Large studies have found that these medications can reduce the risk of serious heart issues, decrease hospital visits, and improve heart health. Although some patients experienced worsening heart failure, this was similar to what is typically expected in these cases. Overall, SGLT2 inhibitors are well-tolerated, and their benefits for heart health appear promising. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for heart failure with a left ventricular assist device (LVAD) focus on managing symptoms and supporting heart function. However, SGLT2 inhibitors (SGLT2i) are unique because they work by helping the kidneys remove excess glucose and sodium from the body, which can benefit heart health. Researchers are excited about SGLT2i because they have shown promise in improving heart failure outcomes by reducing fluid overload and potentially lowering heart stress. This mechanism is different from traditional heart failure treatments, which typically don't target glucose and sodium removal.

What is the effectiveness track record for SGLT2 inhibitors in heart failure patients with LVADs?

Research has shown that SGLT2 inhibitors can help treat heart failure. In this trial, participants in one arm will take an SGLT2 inhibitor for 6 months. Studies have found that these medications can lower the risk of death by 43% and reduce hospital visits by 38% for patients using heart pumps called LVADs. They also help prevent heart failure flare-ups. Additionally, SGLT2 inhibitors can improve heart function and help control blood sugar levels. This type of medication benefits patients at different stages of heart failure, making it a promising option for those with heart issues who use LVADs. ^{1 2 6 7 8}

Who Is on the Research Team?

Mark Belkin, MD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

This trial is for adults over 18 with heart failure who have a left ventricular assist device (LVAD) implanted and haven't been treated with SGLT2 inhibitors yet. They must be able to consent and have an eGFR of at least 30 ml/min/1.73 m². Those with Type 1 diabetes or worse kidney function can't join.

Inclusion Criteria

I have not been treated with SGLT2 inhibitors.

Your kidney function is good, with a filtration rate of at least 30 milliliters per minute per 1.73 square meters.

Able to provide informed consent

Exclusion Criteria

My kidney function is severely reduced.

I have been diagnosed with Type 1 diabetes.

I am under 18 years old.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either SGLT2i or no SGLT2i as part of routine heart failure care for 6 months

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• SGLT2i

Trial Overview The study is looking at the effects of sodium-glucose co-transporter 2 inhibitors (SGLT2i) on patients with heart failure who use LVADs, comparing those who take SGLT2i against those who do not.

How Is the Trial Designed?

Group I: SGLT2i Active Control 1 Intervention

Participants will be asked to take an SGLT2i for 6 months. The SGLT2i and heart failure care will be managed according to routine care, and data will be collected from the participant's medical record.

Group II: No SGLT2i Active Control 1 Intervention

Participants will not be asked to take an SGLT2i. Heart failure care will be managed according to routine care, and data will be collected from the participant's medical record.

SGLT2i is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as SGLT2 inhibitors for:

• Type 2 diabetes
• Heart failure
• Chronic kidney disease
• Cardiovascular risk reduction

Approved in European Union as SGLT2 inhibitors for:

• Type 2 diabetes
• Heart failure
• Chronic kidney disease
• Cardiovascular risk reduction

Approved in Canada as SGLT2 inhibitors for:

• Type 2 diabetes
• Heart failure
• Chronic kidney disease
• Cardiovascular risk reduction

Approved in Japan as SGLT2 inhibitors for:

• Type 2 diabetes
• Heart failure
• Chronic kidney disease
• Cardiovascular risk reduction

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Published Research Related to This Trial

A review of 47 systematic reviews on SGLT-2 inhibitors found that most had low methodological quality, leaving uncertainty about the risks of important side effects in patients with type 2 diabetes.

Canagliflozin and dapagliflozin were linked to an increased risk of genital infections and diabetic ketoacidosis, while dapagliflozin also showed a significant risk for urinary tract infections; however, no SGLT-2 inhibitors were associated with a significant increase in acute kidney injury or bone fractures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events associated with sodium glucose co-transporter 2 inhibitors: an overview of quantitative systematic reviews. Pelletier, R., Ng, K., Alkabbani, W., et al.[2022]

SGLT2 inhibitors, such as dapagliflozin and empagliflozin, not only lower blood sugar but also significantly improve outcomes for patients with heart failure and reduced ejection fraction (HFrEF), even in those without diabetes.

These medications have recently been recognized as essential components of HFrEF treatment, and this article serves as a practical guide for cardiologists on how to start and monitor patients on SGLT2 inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ANMCO statement on the use of sodium-glucose cotransporter 2 inhibitors in patients with heart failure: a practical guide for a streamlined implementation. Di Fusco, SA., Gronda, E., Mocini, E., et al.[2022]

A meta-analysis of 10 randomized controlled trials involving 15,373 heart failure patients found no significant differences in clinical outcomes among the SGLT2 inhibitors empagliflozin, dapagliflozin, canagliflozin, and ertugliflozin regarding heart failure hospitalizations, cardiovascular deaths, and all-cause mortality.

Despite the lack of differences in treatment effects, the analysis highlighted the need for further research due to the variability in study results and the wide confidence intervals observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing the clinical outcomes across different sodium/glucose cotransporter 2 (SGLT2) inhibitors in heart failure patients: a systematic review and network meta-analysis of randomized controlled trials. Teo, YH., Yoong, CSY., Syn, NL., et al.[2022]

SGLT2 inhibitors (SGLT2i) show promising benefits for patients with heart failure (HF), regardless of whether they have diabetes, with strong clinical evidence supporting their use in both heart failure with reduced ejection fraction (HFrEF) and possibly heart failure with preserved ejection fraction (HFpEF).

The mechanisms by which SGLT2i improve heart failure symptoms are complex and include effects on volume regulation, cardiac remodeling, inflammation reduction, and metabolic changes, suggesting that their benefits extend beyond just managing traditional risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SGLT2 Inhibitors and Their Mode of Action in Heart Failure-Has the Mystery Been Unravelled? Pabel, S., Hamdani, N., Luedde, M., et al.[2022]

SGLT2 inhibitors are effective in treating heart failure with reduced ejection fraction (HFrEF) and may also benefit those with preserved ejection fraction (HFpEF), showing significant cardiovascular benefits in clinical trials.

These medications work through mechanisms beyond just lowering blood sugar, such as promoting diuresis and potentially offering additional cardioprotective effects, indicating their role in managing heart failure may expand to other chronic conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pharmacology of SGLT-2 inhibitors in heart failure. Velliou, M., Polyzogopoulou, E., Ventoulis, I., et al.[2023]

SGLT2 inhibitors, commonly used for diabetes, have been shown to significantly reduce hospitalizations for heart failure, indicating their potential as a treatment for heart conditions beyond diabetes.

The review highlights various mechanisms by which SGLT2 inhibitors exert cardioprotective effects, including regulating ion exchange, managing blood volume, remodeling the heart, and improving cardiac energy metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanisms of SGLT2 Inhibitors in Heart Failure and Their Clinical Value. Xie, Y., Wei, Y., Li, D., et al.[2023]

SGLT2 inhibitors, a new class of oral medications for type 2 diabetes, effectively lower blood glucose levels by preventing the reabsorption of glucose and sodium in the kidneys, and they also provide cardiovascular and renal protection.

While SGLT2 inhibitors are generally well-tolerated, they carry risks of serious side effects such as hypoglycemia, hypotension, and infections, necessitating careful patient monitoring to manage these potential complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of sodium glucose co-transporter 2 (SGLT2) inhibitors: A brief summary. Mascolo, A., Di Napoli, R., Balzano, N., et al.[2022]

SGLT2 inhibitors, including canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin, are effective treatments for type 2 diabetes and have shown benefits in heart failure and chronic kidney disease, even in patients without diabetes.

While most side effects of SGLT2 inhibitors, like mild genitourinary infections, are manageable, healthcare providers should be cautious of serious risks such as hypoglycemia, lower limb ischemia, and diabetic ketoacidosis, especially when these drugs are used with insulin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SGLT2 Inhibitors, What the Emergency Physician Needs to Know: A Narrative Review. Lu, H., Lu, H., Kosinski, C., et al.[2021]

SGLT-2 inhibitors, originally used for type 2 diabetes, have been shown to significantly reduce mortality and hospitalization rates in heart failure patients, leading to their inclusion as essential treatments in recent American and European guidelines.

While the exact mechanisms of how SGLT-2 inhibitors improve heart failure outcomes are not fully understood, they are believed to involve various metabolic and hemodynamic effects, highlighting their potential as adjunctive therapy in managing heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SGLT-2 Inhibitor Use in Heart Failure: A Review for Nurses. March, KL., Lukas, JG., Berei, TJ., et al.[2022]

SGLT2 inhibitors, like dapagliflozin and empagliflozin, are effective first-line treatments for type 2 diabetes, especially in patients with cardiovascular disease or heart failure, showing benefits even in those without diabetes.

While SGLT2 inhibitors have a generally favorable safety profile, they can increase the risk of euglycemic diabetic ketoacidosis and genital infections, which requires careful monitoring in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Practical considerations in the use of SGLT2 inhibitors in cardiovascular diseases]. Lu, H., Hullin, R., Yerly, P., et al.[2021]

SGLT2 inhibitors significantly reduce the risk of acute kidney injury (RR 0.75) and show a trend towards lower severe hypoglycemia risk (RR 0.86), indicating a safety benefit in patients with chronic diseases.

However, SGLT2 inhibitors are associated with increased risks of diabetic ketoacidosis (RR 2.57), genital infections (RR 3.75), and volume depletion (RR 1.14), suggesting that these specific adverse events should be closely monitored in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of four SGLT2 inhibitors in three chronic diseases: A meta-analysis of large randomized trials of SGLT2 inhibitors. Qiu, M., Ding, LL., Zhang, M., et al.[2022]

SGLT-2 inhibitors, a new class of diabetes medications, not only help control blood sugar levels but also provide significant cardiovascular benefits, including weight loss, lower blood pressure, and improved kidney function.

Large clinical trials have shown that SGLT-2 inhibitors like Empagliflozin, Canagliflozin, and Dapagliflozin reduce major cardiovascular events, including heart failure hospitalizations, suggesting they may be effective treatments for heart failure as well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review on sodium-glucose cotransporter 2 inhibitor (SGLT2i) in diabetes mellitus and heart failure. Pradhan, A., Vohra, S., Vishwakarma, P., et al.[2020]

Among 139,317 patients with type 2 diabetes and heart failure, only 34% were eligible for SGLT-2 inhibitor therapies based on FDA labeling criteria, indicating that a significant portion of this population may not benefit from these treatments.

Ongoing studies are needed to evaluate the safety and efficacy of SGLT-2 inhibitors in broader patient populations, as current eligibility criteria exclude many hospitalized patients with heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eligibility of sodium-glucose co-transporter-2 inhibitors among patients with diabetes mellitus admitted for heart failure. Sharma, A., Wu, J., Ezekowitz, JA., et al.[2021]

Citations

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A Systematic Review and Meta-Analysis of the Efficacy and ... SGLT2-i effectively improves EF and HbA1c in patients using LVAD. Further adequately powered randomized studies are warranted to ascertain its clinical ...

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The Role of SGLT2-Inhibitors Across All Stages of Heart ... SGLT2i have demonstrated a pivotal role in preventing and treating HF across the entire spectrum of left ventricular ejection fraction (LVEF), regardless of the ...

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SGLT2 inhibitors and cardiovascular outcomes in patients ... SGLT2i use in LVAD patients reduced all-cause death by 43% and hospitalization by 38%. •. SGLT2i use was linked to fewer heart failure exacerbations, ...

4. ahajournals.org ahajournals.org/doi/10.1161/JAHA.119.013389

SGLT‐2 Inhibitors in Heart Failure: Current Management ... Several established treatments for HFrEF have shown no efficacy in trials of HFpEF, with no benefit demonstrated in the CHARM‐Preserved ( ...

5. bmj.com bmj.com/content/387/bmj-2024-080925

SGLT-2 inhibitors and mortality among patients with heart ... This database study showed that the use of SGLT-2 inhibitors was significantly associated with lower risk of all cause and cardiovascular ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2666602222000714

Safety and effects of SGLT-2 inhibitor use among LVAD ... Several major trials have recently shown SGLT-2 inhibitors (SGLT2i) confer a reduced risk of adverse cardiovascular (CV) events in patients with heart failure.

7. jhltonline.org jhltonline.org/article/S1053-2498(24)01070-2/fulltext

Efficacy and Safety of SGLT2 Inhibitors in Patients with a ... Similar to benchmarks, a total of 23 patients (34.8%) experienced a worsening heart failure event with a median time to event at 90 days after SGLT2 initiation.

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Effect of sodium-glucose cotransporter-2 inhibitor (SGLT2-i) in ... SGLT2-i effectively improves HbA1c and diuretic dose in patients using LVAD. Further randomized studies with a large number of participants may be warranted.