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Angiotensin Receptor Neprilysin Inhibitor

Entresto + Aprepitant for Heart Failure

Phase 4

Recruiting

Led By Nancy J. Brown, MD

Research Sponsored by Yale University

Eligibility Criteria Checklist

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

Must have

EF ≤55%, and history of symptoms of New York Heart Association (NYHA) class I, II, or III heart failure (HF)

History of symptoms of New York Heart Association (NYHA) class I, II, or III heart failure (HF)

Must not have

Type 1 diabetes

History of ventricular arrhythmia with syncopal episodes

Timeline

Screening 3 weeks

Treatment Varies

Follow Up over six hours on each of the four study days

Awards & highlights

Drug Has Already Been Approved

Pivotal Trial

Summary

This trial is testing whether a drug called Entresto, which is given to people with heart failure, is more effective when taken with or without another drug called Aprepitant.

Who is the study for?

This trial is for black and white men and women, aged 18 or older, with heart failure (NYHA Class I-III) and an ejection fraction (EF) ≤55%. Participants must have stable symptoms, no recent hospitalizations for heart failure, not be on LCZ696 currently, and if female and of childbearing potential, use reliable contraception. Excluded are those with allergies to study drugs or related chemicals, history of angioedema or certain cardiovascular events within the last six months.

What is being tested?

The trial tests how blood pressure responds to a combination of Aprepitant vs Placebo during initiation and steady-state doses of Entresto (LCZ696). It's a double-blind study where participants randomly receive either the drug or placebo in two phases: starting dose (50 mg) and maintenance dose (200 mg bid or highest tolerated).

What are the potential side effects?

Potential side effects may include allergic reactions to medication components; changes in kidney function as measured by substances like Para-aminohippurate; contrast-related reactions due to Iohexol; gastrointestinal issues affecting drug absorption; hormonal imbalances impacting diabetes control.

Eligibility Criteria

Inclusion Criteria

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

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My heart's pumping ability is reduced, and I've had mild to moderate heart failure symptoms.

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I have experienced mild to moderate heart failure symptoms.

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I am 18 years old or older.

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I am not currently taking LCZ696.

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My heart pumps less blood than normal but my condition is stable.

Exclusion Criteria

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

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I have Type 1 diabetes.

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I have had fainting spells due to irregular heartbeats.

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I might need heart or neck artery surgery within the next 6 months.

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I have a stomach or bowel problem that affects how medicines work in my body.

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I have low blood pressure or symptoms of it.

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I am currently taking lithium.

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I use my asthma inhaler more than once a week.

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I have not taken more than 5 mg of prednisone or similar steroids regularly in the past year.

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I understand the details and risks of the study.

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My kidney function is significantly reduced.

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I have had a serious brain condition like a stroke or seizure with lasting effects.

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My liver is not working well due to severe scarring.

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I have a significant blockage in the heart's outflow tract.

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I have a history of immune or blood disorders.

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I have a history of cancer, not including non-melanoma skin cancer, that is not considered cured.

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I have had pancreatitis or have known pancreatic lesions.

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I have a slow heartbeat or heart block without a pacemaker.

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I haven't had major heart or blood vessel surgery in the last 6 months.

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My diabetes is not well-managed, with a HgbA1c level over 9%.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ over six hours on each of four study days

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~over six hours on each of four study days

This trial's timeline: 3 weeks for screening, Varies for treatment, and over six hours on each of four study days for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Mean arterial pressure (MAP)

Urine sodium excretion

Secondary study objectives

Glomerular filtration rate

Heart rate

Renal plasma flow

+2 more

Awards & Highlights

Drug Has Already Been Approved

The FDA has already approved this drug, and is just seeking more data.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

4Treatment groups

Experimental Treatment

Group I: placebo, aprepitant, placebo, aprepitantExperimental Treatment5 Interventions

After a 48-hr washout, participants in this arm will be given LCZ696 50 mg and placebo (vehicle). After a 96-hr washout period, subjects will be given LCZ696 50 mg and aprepitant. Participants will then undergo uptitration of LCZ696 over seven weeks. On the 7th and 10th days of the 200 mg bid or highest tolerated dose of LCZ696, participants in this arm will receive placebo and aprepitant, respectively.

Group II: placebo, aprepitant, aprepitant, placeboExperimental Treatment5 Interventions

Group III: aprepitant, placebo, placebo, aprepitantExperimental Treatment5 Interventions

After a 48-hr washout, participants in this arm will be given LCZ696 50 mg and aprepitant. After a 96-hr washout period, subjects will be given LCZ696 50 mg and placebo. Participants will then undergo uptitration of LCZ696 over seven weeks. On the 7th and 10th days of the 200 mg bid or highest tolerated dose of LCZ696, participants in this arm will receive placebo and aprepitant, respectively.

Group IV: aprepitant, placebo, aprepitant, placeboExperimental Treatment5 Interventions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

LCZ 696

2018

N/A

~100

Aprepitant

2008

Completed Phase 4