What side effects are associated with this type of intervention?

Common treatments for heart failure, including beta-blockers, ACE inhibitors, ARBs, diuretics, SGLT2 inhibitors, and neprilysin inhibitors, have a range of side effects. Beta-blockers can cause fatigue, bradycardia, and hypotension. ACE inhibitors and ARBs may lead to cough, hyperkalemia, and renal impairment. Diuretics often result in electrolyte imbalances, dehydration, and renal dysfunction. SGLT2 inhibitors can cause urinary tract infections and genital infections. Neprilysin inhibitors, when combined with ARBs, may cause hypotension, hyperkalemia, and renal impairment. It is important to monitor for these side effects and manage them appropriately in patients with heart failure.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of heart failure, including ACE inhibitors (e.g., enalapril), beta-blockers (e.g., metoprolol), and diuretics (e.g., furosemide). More recently, angiotensin receptor-neprilysin inhibitors (ARNIs) like sacubitril/valsartan and sodium-glucose co-transporter-2 (SGLT2) inhibitors such as dapagliflozin have been approved for heart failure treatment. These newer classes of drugs have shown efficacy in improving outcomes in heart failure patients, including those with preserved ejection fraction (HFpEF).

What other types of research exist?

Promising novel alternatives to LY3540378 for heart failure patients include: 1) SGLT2 inhibitors (e.g., dapagliflozin and empagliflozin) which have shown benefits in heart failure with preserved ejection fraction (HFpEF). 2) Vericiguat, a soluble guanylate cyclase stimulator, which has been approved for reducing the risk of cardiovascular death and heart failure hospitalization. 3) Omecamtiv mecarbil, a cardiac myosin activator, which improves cardiac contractility. These alternatives offer different mechanisms of action and have demonstrated efficacy and safety in clinical trials.

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Not Applicable

LY3540378 for Chronic Heart Failure

Phase 2

Recruiting

Research Sponsored by Eli Lilly and Company

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Prior chronic treatment, or prescription, with a loop diuretic (for example, furosemide, torsemide, bumetanide) for ≥30 days prior to the index event. Medical records, discharge notes and physician referral letters may serve as documentation for prior chronic treatment with a loop diuretic.

Documented LVEF of ≥50% within 12 months prior to screening; as measured by echocardiography, radionuclide ventriculography, invasive angiography, magnetic resonance imaging (MRI), or computerized tomograph (CT). Evidence of documentation of LVEF of ≥50% may also include participant medical records, discharge notes or a referral letter from the participant's physician or referring physician that details the participant's medical history.

Must not have

Have had Left Ventricular assist device (LVAD) or cardiac transplantation or have cardiac transplantation planned during the study.

Have hypertrophic cardiomyopathy (obstructive or nonobstructive), restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, cardiac sarcoidosis, known amyloid cardiomyopathy, or inherited cardiomyopathy.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline, week 26

Summary

This trial is testing a new medication called LY3540378 to see if it can help adults whose heart failure is getting worse even though their heart pumps normally. The goal is to find out if this medication can improve their heart function and safety.

Who is the study for?

This trial is for adults with chronic heart failure who've had a recent worsening event requiring intravenous diuretics. They must have had a preserved ejection fraction (≥50%) documented within the last year and been on loop diuretics for at least 30 days prior to their worsening event. Exclusions include recent acute coronary events, uncorrected thyroid disease, certain cardiomyopathies, severe lung diseases like COPD, or planned heart surgeries.

What is being tested?

The study tests LY3540378's effectiveness and safety against a placebo in improving conditions for those with worsening chronic heart failure but preserved ejection fraction. Participants will be randomly assigned to receive either the investigational drug or an inactive substance without knowing which one they're getting.

What are the potential side effects?

While specific side effects of LY3540378 are not listed here, common side effects in trials involving heart failure medications may include kidney problems, low blood pressure, changes in electrolyte levels, dizziness or fatigue. The exact side effects will be monitored throughout the trial.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been on a water pill for heart or kidney issues for at least 30 days.

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My heart's pumping ability is confirmed to be good.

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I was recently hospitalized for heart failure and needed strong water pills.

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I have symptoms of heart failure.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have or will have a heart assist device or heart transplant.

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I have a diagnosed heart muscle condition.

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I've had recent major heart surgery or plan to have one during the study.

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I need oxygen daily due to severe lung disease, but only at night is okay.

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I have a thyroid condition that hasn't been treated.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline, week 26

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline, week 26

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline, week 26 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Change from Baseline in Estimated Glomerular Filtration Rate (eGFR)

Trial Design

4Treatment groups

Experimental Treatment

Placebo Group

Group I: LY3540378 Dose 3Experimental Treatment1 Intervention

Participants will receive LY3540378 SC.

Group II: LY3540378 Dose 2Experimental Treatment1 Intervention

Participants will receive LY3540378 SC.

Group III: LY3540378 Dose 1Experimental Treatment1 Intervention

Participants will receive LY3540378 subcutaneously (SC).

Group IV: PlaceboPlacebo Group1 Intervention

Participants will be given placebo SC.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

LY3540378

2021

Completed Phase 1

~140

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Heart Failure (HF) work through various mechanisms to alleviate symptoms and improve heart function. ACE inhibitors and angiotensin receptor blockers (ARBs) reduce the workload on the heart by dilating blood vessels, thereby lowering blood pressure and decreasing fluid buildup. Beta-blockers slow the heart rate and reduce blood pressure, which helps to improve heart function and reduce the risk of arrhythmias. Diuretics help to remove excess fluid from the body, reducing symptoms like swelling and shortness of breath. Newer agents like SGLT2 inhibitors, originally used for diabetes, have shown benefits in reducing hospitalizations and improving cardiovascular outcomes in HF patients. These treatments are crucial as they address the underlying pathophysiology of HF, improving quality of life and survival rates for patients.