← Back to Search

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
Select...
My heart's pumping ability is reduced, and I've had mild to moderate heart failure symptoms.
Select...
I have experienced mild to moderate heart failure symptoms.
Select...
I am 18 years old or older.
Select...
I am not currently taking LCZ696.
Select...
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:
Select...
I have Type 1 diabetes.
Select...
I have had fainting spells due to irregular heartbeats.
Select...
I might need heart or neck artery surgery within the next 6 months.
Select...
I have a stomach or bowel problem that affects how medicines work in my body.
Select...
I have low blood pressure or symptoms of it.
Select...
I am currently taking lithium.
Select...
I use my asthma inhaler more than once a week.
Select...
I have not taken more than 5 mg of prednisone or similar steroids regularly in the past year.
Select...
I understand the details and risks of the study.
Select...
My kidney function is significantly reduced.
Select...
I have had a serious brain condition like a stroke or seizure with lasting effects.
Select...
My liver is not working well due to severe scarring.
Select...
I have a significant blockage in the heart's outflow tract.
Select...
I have a history of immune or blood disorders.
Select...
I have a history of cancer, not including non-melanoma skin cancer, that is not considered cured.
Select...
I have had pancreatitis or have known pancreatic lesions.
Select...
I have a slow heartbeat or heart block without a pacemaker.
Select...
I haven't had major heart or blood vessel surgery in the last 6 months.
Select...
My diabetes is not well-managed, with a HgbA1c level over 9%.

Timeline

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
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 aprepitant and placebo, respectively.
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
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 aprepitant and placebo, respectively.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
LCZ 696
2018
N/A
~100
Aprepitant
2008
Completed Phase 4
~1900
Placebo
1995
Completed Phase 3
~2670
Iohexol
2016
Completed Phase 4
~1920

Find a Location

Who is running the clinical trial?

Yale UniversityLead Sponsor
1,919 Previous Clinical Trials
3,040,275 Total Patients Enrolled
34 Trials studying Heart Failure
58,051 Patients Enrolled for Heart Failure
Nancy J. Brown, MDPrincipal InvestigatorYale University
2 Previous Clinical Trials
46 Total Patients Enrolled

Media Library

LCZ 696 (Angiotensin Receptor Neprilysin Inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT04649229 — Phase 4
Heart Failure Research Study Groups: aprepitant, placebo, aprepitant, placebo, aprepitant, placebo, placebo, aprepitant, placebo, aprepitant, aprepitant, placebo, placebo, aprepitant, placebo, aprepitant
Heart Failure Clinical Trial 2023: LCZ 696 Highlights & Side Effects. Trial Name: NCT04649229 — Phase 4
LCZ 696 (Angiotensin Receptor Neprilysin Inhibitor) 2023 Treatment Timeline for Medical Study. Trial Name: NCT04649229 — Phase 4
Heart Failure Patient Testimony for trial: Trial Name: NCT04649229 — Phase 4
~14 spots leftby Jul 2025
Unbiased ResultsWe believe in providing patients with all the options.
Your Data Stays Your DataWe only share your information with the clinical trials you're trying to access.
Verified Trials OnlyAll of our trials are run by licensed doctors, researchers, and healthcare companies.
Back to top