The Effect of Neprilysin (LCZ696) on Exercise Tolerance in Patients With Heart Failure

NCT03190304 | Completed Phase 4 DMC

• 1 other identifier: NEPRIExTol-HF Trial
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Heart Failure; Exercise Tolerance; Vasodilation; Body Composition; Muscle Strength

Outcome Measures

Primary Outcomes (1)

• Exercise tolerance

  To test the effect of treatments on peak oxygen consumption

  6 months

Secondary Outcomes (4)

• Walking distance

  6 months

• Muscle vasodilation

  6 months

• Muscle strength

  6 months

• Body composition

  6 months

Study Arms (2)

Enalapril

ACTIVE COMPARATOR

Enalapril at a dose of 10 mg twice daily for 6 months

Drug: Enalapril

Neprilysin (LCZ696)

EXPERIMENTAL

LCZ696 at a dose of 200 mg twice daily for 6 months

Drug: Neprilysin

Interventions

Neprilysin DRUG

To compare the effect of Enalapril and Neprilysin on exercise tolerance in patients with heart failure

Also known as: LCZ696

Neprilysin (LCZ696)

Enalapril DRUG

To compare the effect of Enalapril and Neprilysin on exercise tolerance in patients with heart failure

Also known as: Angiotensin converting enzyme inhibitor

Enalapril

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Sao Paulo General Hospital: lead

Study Sites (1)

Marcelo Rodrigues dos Santos

São Paulo, São Paulo, 05403-900, Brazil

Location

Related Publications (1)

• 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.

  PMID: 33992607 DERIVED

MeSH Terms

Conditions

Heart Failure; Aneurysm

Interventions

Neprilysin; sacubitril and valsartan sodium hydrate drug combination; Enalapril; Angiotensin-Converting Enzyme Inhibitors

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Antigens, Neoplasm; Antigens; Biological Factors; Biomarkers, Tumor; Biomarkers; Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Antonio P Barretto, PhD

  Heart Institute (InCor), University of Sao Paulo Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: double-blind, randomized clinical trial

Study Record Dates

• First Submitted: June 14, 2017
• First Posted: June 16, 2017
• Study Start: June 14, 2017
• Primary Completion: September 14, 2020
• Study Completion: September 23, 2020
• Last Updated: October 22, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)