- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03190304
The Effect of Neprilysin (LCZ696) on Exercise Tolerance in Patients With Heart Failure (NEPRIExTol)
October 21, 2020 updated by: University of Sao Paulo General Hospital
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.
Study Overview
Status
Completed
Intervention / Treatment
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 Type
Interventional
Enrollment (Actual)
52
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
SP
-
São Paulo, SP, Brazil, 05403-900
- Marcelo Rodrigues dos Santos
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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)
Exclusion Criteria:
- 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.
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Enalapril
Enalapril at a dose of 10 mg twice daily for 6 months
|
To compare the effect of Enalapril and Neprilysin on exercise tolerance in patients with heart failure
Other Names:
|
Experimental: Neprilysin (LCZ696)
LCZ696 at a dose of 200 mg twice daily for 6 months
|
To compare the effect of Enalapril and Neprilysin on exercise tolerance in patients with heart failure
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Exercise tolerance
Time Frame: 6 months
|
To test the effect of treatments on peak oxygen consumption
|
6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Walking distance
Time Frame: 6 months
|
To test the effect of treatments on 6 minutes walking test
|
6 months
|
Muscle vasodilation
Time Frame: 6 months
|
To test the effect of treatments on forearm blood flow evaluated by venous occlusion plethysmography
|
6 months
|
Muscle strength
Time Frame: 6 months
|
To test the effect of treatments on muscle strength evaluated by handgrip
|
6 months
|
Body composition
Time Frame: 6 months
|
To test the effect of treatments on lean muscle mass evaluated by dual energy x-ray absorptiometry
|
6 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Antonio P Barretto, PhD, Heart Institute (InCor), University of Sao Paulo Medical School
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 14, 2017
Primary Completion (Actual)
September 14, 2020
Study Completion (Actual)
September 23, 2020
Study Registration Dates
First Submitted
June 14, 2017
First Submitted That Met QC Criteria
June 14, 2017
First Posted (Actual)
June 16, 2017
Study Record Updates
Last Update Posted (Actual)
October 22, 2020
Last Update Submitted That Met QC Criteria
October 21, 2020
Last Verified
March 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- NEPRIExTol-HF Trial
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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