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Angiotensin Receptor Blocker/Neprilysin Inhibitor

LCZ696 for Heart Failure

Phase 4
Recruiting
Led By Nancy J. Brown, M.D.
Research Sponsored by Vanderbilt University Medical Center
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
Stable patients with a reduced ejection fraction (EF) ≤40%
History of symptoms of New York Heart Association (NYHA) class I, II, or III heart failure (HF)
Must not have
Mental conditions rendering the subject unable to understand the nature, scope, and possible consequences of the study
Symptomatic hypotension and/or a systolic blood pressure (SBP)<100 mmHg at screening or <95 mmHg during the study
Timeline
Screening 3 weeks
Treatment Varies
Follow Up over six hours on each of four study days
Awards & highlights
Drug Has Already Been Approved
Pivotal Trial

Summary

This trial is testing the hypothesis that the effects of LCZ696 on blood pressure, natriuresis, and diuresis at initiation are due to the inhibition of neprilysin, which degrades endogenous bradykinin. The study will enroll 80 subjects with stable heart failure who will be given LCZ696 50 mg and either the bradykinin B2 receptor antagonist icatibant or placebo vehicle in random order (double-blind).

Who is the study for?
This trial is for stable heart failure patients with reduced ejection fraction (EF ≤40%), not hospitalized in the last six months, and on a stable dose of ACEi or ARB and beta blocker. It includes both men and women who are either postmenopausal, surgically sterilized, or using reliable birth control if of childbearing potential.
What is being tested?
The study tests LCZ696's effects on blood pressure, natriuresis (sodium excretion), and diuresis (urine production) in heart failure patients. It involves stopping current ACEi/ARB medication, taking LCZ696 with placebo or icatibant (a bradykinin B2 receptor antagonist), followed by an up-titration protocol to assess changes.
What are the potential side effects?
Potential side effects may include hypotension due to vasodilation from increased bradykinin levels when starting LCZ696. Other risks involve reactions to contrast agents used during testing, as well as general drug-related allergies or sensitivities.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
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My heart pumps less blood than normal but my condition is stable.
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I have experienced symptoms of heart failure but can still perform daily activities.
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I haven't been hospitalized in the last 6 months.
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I am not currently taking LCZ696.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
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I understand the details and risks of the study.
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I have low blood pressure or symptoms of it.
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I have not taken long-term steroid pills in the past year.
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I am currently taking lithium.
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I have had fainting spells due to irregular heartbeats.
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I have a significant blockage in the heart's outflow tract.
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I have a slow heartbeat or heart block without a pacemaker.
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I might need heart or neck artery surgery within the next 6 months.
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My type 2 diabetes is not well-managed, with a HgbA1c over 9%.
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I am not allergic to the study drugs or similar medications.
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I have had pancreatitis or have known pancreatic lesions.
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I have a history of immune or blood disorders.
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I use my asthma inhaler more than once a week.
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I have had a serious brain condition like a stroke or seizure.
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I have a history of cancer, except for non-dangerous skin cancer.
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I have Type 1 diabetes.
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My liver tests (AST or ALT) are more than three times the normal range.
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My kidney function is significantly reduced.
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I have a digestive issue that affects how my body absorbs medication.

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
Urine sodium excretion
mean arterial pressure
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, icatibant, placebo, icatibantExperimental 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 icatibant. 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 icatibant, respectively.
Group II: placebo, icatibant, icatibant, 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 icatibant. 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 icatibant and placebo, respectively.
Group III: icatibant, placebo, placebo, icatibantExperimental Treatment5 Interventions
After a 48-hr washout, participants in this arm will be given LCZ696 50 mg and icatibant. 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 icatibant, respectively.
Group IV: icatibant, placebo, icatibant placeboExperimental Treatment5 Interventions
After a 48-hr washout, participants in this arm will be given LCZ696 50 mg and icatibant. 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 icatibant and placebo, respectively.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
placebo
2010
Completed Phase 4
~6580
LCZ 696
2018
N/A
~100
Icatibant
2009
Completed Phase 4
~610
Iohexol
2016
Completed Phase 4
~1920

Find a Location

Who is running the clinical trial?

Vanderbilt University Medical CenterLead Sponsor
900 Previous Clinical Trials
939,426 Total Patients Enrolled
14 Trials studying Heart Failure
6,043 Patients Enrolled for Heart Failure
Nancy J. Brown, M.D.Principal Investigator - Vanderbilt University Medical Center
Vanderbilt University Medical Center
1 Previous Clinical Trials
455 Total Patients Enrolled

Media Library

LCZ 696 (Angiotensin Receptor Blocker/Neprilysin Inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT04113109 — Phase 4
Heart Failure Research Study Groups: icatibant, placebo, icatibant placebo, placebo, icatibant, placebo, icatibant, placebo, icatibant, icatibant, placebo, icatibant, placebo, placebo, icatibant
Heart Failure Clinical Trial 2023: LCZ 696 Highlights & Side Effects. Trial Name: NCT04113109 — Phase 4
LCZ 696 (Angiotensin Receptor Blocker/Neprilysin Inhibitor) 2023 Treatment Timeline for Medical Study. Trial Name: NCT04113109 — Phase 4
~9 spots leftby Jul 2025
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