Heart FailurePhase 4NEPRIExTolNCT03190304
The Effect of Neprilysin (LCZ696) on Exercise Tolerance in Patients With Heart Failure
A Phase 4 study testing Neprilysin and Enalapril in people with Heart Failure and Exercise Tolerance, run by University of Sao Paulo General Hospital at 1 site in Brazil.
Trial summary
Studies with new drugs in the treatment of heart failure (HF), such as the combination of valsartan/sacubitril, also known as LCZ696, have demonstrated important clinical impact on the morbidity and mortality outcomes in HF population. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure, Exercise Tolerance, Vasodilation
- What is being tested?
- Neprilysin and Enalapril
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 1 siteBrazil
- Study dates
- 14 Jun 2017to 23 Sep 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Symptomatic patients with heart failure (men and women) aged >18 years,
- Functional class II, III or IV by the New York Heart Association (NYHA)
- Left ventricular ejection fraction <35%
- Ischemic and nonischemic etiology
- Type B natriuretic peptide (BNP) >150 pg/ml (or pro-BNP [N-terminal-proBNP] ≥ 600 pg / ml) or if the patient was hospitalized for cardiac decompensation within the preceding 12 months, BNP >100 pg/ml (or N-terminal-proBNP ≥ 400 pg / ml)
Who cannot join
- History of hypersensitivity or allergy to any of the study drugs, drugs of similar chemical classes, ACE inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), or neprilysin inhibitors, as well as known or suspected contraindications to the study drugs.
- Previous history of intolerance to recommended target doses of ACEIs or ARBs.
- Known history of angioedema.
- Requirement for treatment with both ACEIs and ARBs.
- Current acute decompensated heart failure (exacerbation of chronic heart failure manifested by signs and symptoms that may require intravenous therapy).
- Symptomatic hypotension.
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- Estimated glomerular filtration rate (eGFR) <30%.
- Serum potassium >5.4 mmol/L.
- Acute coronary syndrome, stroke, transient ischaemic attack, cardiac, carotid, or other major cardiovascular surgery, percutaneous coronary intervention, or carotid angioplasty within the 3 months.
- Coronary or carotid artery disease likely to require surgical or percutaneous intervention within the 6 months.
- Implantation of a cardiac resynchronization therapy (CRT) device within 3 months or intent to implant a CRT.
- History of heart transplant or on a transplant list or with left ventricular (LV) assistance device.
- History of severe pulmonary disease.
- Diagnosis of peripartum- or chemotherapy-induced cardiomyopathy within the 12 months.
- Documented untreated ventricular arrhythmia with syncopal episodes within the 3 months.
- Symptomatic bradycardia or second- or third-degree atrioventricular block without a pacemaker.
- Presence of haemodynamically significant mitral and/or aortic valve disease, except mitral regurgitation secondary to LV dilatation.
- Presence of other haemodynamically significant obstructive lesions of the LV outflow tract, including aortic and subaortic stenosis.
- Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of study drugs, including, but not limited to, any of the following: History of active inflammatory bowel disease during the 12 months. Active duodenal or gastric ulcers during the 3 months. Evidence of hepatic disease as determined by any one of the following: aspartate aminotransferase or alanine aminotransferase values exceeding 2x upper limit of normal, history of hepatic encephalopathy, history of oesophageal varices, or history of porto-caval shunt. Current treatment with cholestyramine or colestipol resins.
- Presence of any other disease with a life expectancy of <5 years.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of NEPRIlysin (LCZ696) on EXercise TOLerance, Muscle Vasodilatation, Muscle Strength and Body Composition in Patients With Heart Failure - NEPRIExTol-HF Trial
Studies with new drugs in the treatment of heart failure (HF), such as the combination of valsartan/sacubitril, also known as LCZ696, have demonstrated important clinical impact on the morbidity and mortality outcomes in HF population. However, the effect of LCZ696 on the pathophysiological mechanisms of HF such as exercise tolerance (peak VO2) and peripheral muscle blood flow is not known. Since LCZ696 is a new drug with promising effects on the treatment of HF, the objective of the present study will be to evaluate the effect of LCZ696 in patients with HF on: 1) peak VO2, 2) 6-minute walk test, 3) peripheral muscle blood flow, 4) muscle strength, and 5) body composition.
Read the detailed description
Heart failure (HF) with reduced ventricular ejection fraction is a disease that affects around 5.7 million people in the United States, with a mortality rate of approximately 50% within 5 years. HF is characterized by an exacerbation of the renin-angiotensin-aldosterone system (RAAS), which leads to an increase in sympathetic nerve outflow, peripheral vasoconstriction, and reduced functional capacity. Moreover, many clinical trials have been developed for the treatment of HF patients focused on inhibition of RAAS, such as enalapril. Nevertheless, hospitalization and mortality rates in this population are excessive. However, studies with new drugs, such as the combination of valsartan/sacubitril, also known as LCZ696, have demonstrated important clinical impact on the morbidity and mortality outcomes in HF population. However, the effect of LCZ696 on the pathophysiological mechanisms of HF such as exercise tolerance (peak VO2) and peripheral muscle blood flow is not known. Since LCZ696 is a new drug with promising effects on the treatment of HF, the objective of the present study will be to evaluate the effect of LCZ696 in patients with HF on: 1) peak VO2, 2) 6-minute walk test, 3) peripheral muscle blood flow, 4) muscle strength, and 5) body composition.
- Being tested
- Neprilysin, Enalapril
- Medical subject headings
- Heart Failure, Aneurysm
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NeprilysinDrug
Also called LCZ696
To compare the effect of Enalapril and Neprilysin on exercise tolerance in patients with heart failure
EnalaprilDrug
Also called Angiotensin converting enzyme inhibitor
To compare the effect of Enalapril and Neprilysin on exercise tolerance in patients with heart failure
| Study group | Role | What they receive |
|---|---|---|
| Enalapril | Active comparator | Enalapril at a dose of 10 mg twice daily for 6 months Receives: Drug: Enalapril |
| Neprilysin (LCZ696) | Experimental | LCZ696 at a dose of 200 mg twice daily for 6 months Receives: Drug: Neprilysin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Exercise tolerance
To test the effect of treatments on peak oxygen consumption
Measured: 6 months
Secondary outcomes (4)
Walking distance
To test the effect of treatments on 6 minutes walking test
Measured: 6 months
Muscle vasodilation
To test the effect of treatments on forearm blood flow evaluated by venous occlusion plethysmography
Measured: 6 months
Muscle strength
To test the effect of treatments on muscle strength evaluated by handgrip
Measured: 6 months
Body composition
To test the effect of treatments on lean muscle mass evaluated by dual energy x-ray absorptiometry
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2017
- Study start14 Jun 2017
- Primary completion14 Sep 2020
- Study completion23 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by University of Sao Paulo General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- double-blind, randomized clinical trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Antonio P Barretto, PhD, Principal investigator, Heart Institute (InCor), University of Sao Paulo Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03190304
- Sponsor's protocol ID
- NEPRIExTol-HF Trial
- Acronym
- NEPRIExTol
- Status last verified
- Mar 2020
- First submitted
- 14 Jun 2017
- Last updated
- 22 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Dos Santos MR, Alves MNN, Jordao CP, Pinto CEN, Correa KTS, de Souza FR, da Fonseca GWP, Tomaz Filho J, Costa M, Pereira RMR, Negrao CE, Barretto ACP. Sacubitril/valsartan versus enalapril on exercise capacity in patients with heart failure with reduced ejection fraction: A randomized, double-blind, active-controlled study. Am Heart J. 2021 Sep;239:1-10. doi: 10.1016/j.ahj.2021.05.005. Epub 2021 May 14.
PubMed 33992607
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of NEPRIlysin (LCZ696) on EXercise TOLerance, Muscle Vasodilatation, Muscle Strength and Body Composition in Patients With Heart Failure - NEPRIExTol-HF Trial
- ClinicalTrials.gov ID
- NCT03190304
- Acronym / sponsor ID
- NEPRIExTol / NEPRIExTol-HF Trial
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- University of Sao Paulo General HospitalUniversity, hospital or other
- Study start
- 14 Jun 2017 (actual)
- Primary completion
- 14 Sep 2020 (actual)
- Study completion
- 23 Sep 2020 (actual)
- First posted
- 16 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Studies with new drugs in the treatment of heart failure (HF), such as the combination of valsartan/sacubitril, also known as LCZ696, have demonstrated important clinical impact on the morbidity and mortality outcomes in HF population. However, the effect of LCZ696 on the pathophysiological mechanisms of HF such as exercise tolerance (peak VO2) and peripheral muscle blood flow is not known. Since LCZ696 is a new drug with promising effects on the treatment of HF, the objective of the present study will be to evaluate the effect of LCZ696 in patients with HF on: 1) peak VO2, 2) 6-minute walk test, 3) peripheral muscle blood flow, 4) muscle strength, and 5) body composition.
Detailed description
Heart failure (HF) with reduced ventricular ejection fraction is a disease that affects around 5.7 million people in the United States, with a mortality rate of approximately 50% within 5 years. HF is characterized by an exacerbation of the renin-angiotensin-aldosterone system (RAAS), which leads to an increase in sympathetic nerve outflow, peripheral vasoconstriction, and reduced functional capacity. Moreover, many clinical trials have been developed for the treatment of HF patients focused on inhibition of RAAS, such as enalapril. Nevertheless, hospitalization and mortality rates in this population are excessive. However, studies with new drugs, such as the combination of valsartan/sacubitril, also known as LCZ696, have demonstrated important clinical impact on the morbidity and mortality outcomes in HF population. However, the effect of LCZ696 on the pathophysiological mechanisms of HF such as exercise tolerance (peak VO2) and peripheral muscle blood flow is not known. Since LCZ696 is a new drug with promising effects on the treatment of HF, the objective of the present study will be to evaluate the effect of LCZ696 in patients with HF on: 1) peak VO2, 2) 6-minute walk test, 3) peripheral muscle blood flow, 4) muscle strength, and 5) body composition.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- double-blind, randomized clinical trial
| Arm | Type | Receives |
|---|---|---|
| Enalapril | Active comparator | Drug: EnalaprilEnalapril at a dose of 10 mg twice daily for 6 months |
| Neprilysin (LCZ696) | Experimental | Drug: NeprilysinLCZ696 at a dose of 200 mg twice daily for 6 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Symptomatic patients with heart failure (men and women) aged >18 years,
- Functional class II, III or IV by the New York Heart Association (NYHA)
- Left ventricular ejection fraction <35%
- Ischemic and nonischemic etiology
- Type B natriuretic peptide (BNP) >150 pg/ml (or pro-BNP [N-terminal-proBNP] ≥ 600 pg / ml) or if the patient was hospitalized for cardiac decompensation within the preceding 12 months, BNP >100 pg/ml (or N-terminal-proBNP ≥ 400 pg / ml)
Key exclusion criteria (20 listed)
- History of hypersensitivity or allergy to any of the study drugs, drugs of similar chemical classes, ACE inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), or neprilysin inhibitors, as well as known or suspected contraindications to the study drugs.
- Previous history of intolerance to recommended target doses of ACEIs or ARBs.
- Known history of angioedema.
- Requirement for treatment with both ACEIs and ARBs.
- Current acute decompensated heart failure (exacerbation of chronic heart failure manifested by signs and symptoms that may require intravenous therapy).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NeprilysinAlso: LCZ696To compare the effect of Enalapril and Neprilysin on exercise tolerance in patients with heart failure | Drug | Neprilysin (LCZ696) |
| EnalaprilAlso: Angiotensin converting enzyme inhibitorTo compare the effect of Enalapril and Neprilysin on exercise tolerance in patients with heart failure | Drug | Enalapril |
Primary outcome
Exercise tolerance
Time frame: 6 months
To test the effect of treatments on peak oxygen consumption
4 secondary outcomes
Walking distance
Time frame: 6 months
Muscle vasodilation
Time frame: 6 months
Muscle strength
Time frame: 6 months
Body composition
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2020.
- Derived from this study: PubMed 33992607Dos Santos MR, Alves MNN, Jordao CP, Pinto CEN, Correa KTS, de Souza FR, da Fonseca GWP, Tomaz Filho J, Costa M, Pereira RMR, Negrao CE, Barretto ACP. Sacubitril/valsartan versus enalapril on exercise capacity in patients with heart failure with reduced ejection fraction: A randomized, double-blind, active-controlled study. Am Heart J. 2021 Sep;239:1-10. doi: 10.1016/j.ahj.2021.05.005. Epub 2021 May 14.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Antonio P Barretto, PhD principal investigator
Heart Institute (InCor), University of Sao Paulo Medical School
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Neprilysin and Enalapril in people with Heart Failure and Exercise Tolerance, run by University of Sao Paulo General Hospital at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Exercise tolerance (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03190304, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2020.