Ignite Creation Date:
2025-12-24 @ 7:50 PM
Ignite Modification Date:
2026-01-04 @ 3:30 PM
Study NCT ID:
NCT03190304
Status:
COMPLETED
Last Update Posted:
2020-10-22
First Post:
2017-06-14
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
The Effect of Neprilysin (LCZ696) on Exercise Tolerance in Patients With Heart Failure
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006333', 'term': 'Heart Failure'}, {'id': 'D000783', 'term': 'Aneurysm'}], 'ancestors': [{'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D014652', 'term': 'Vascular Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D015260', 'term': 'Neprilysin'}, {'id': 'C549068', 'term': 'sacubitril and valsartan sodium hydrate drug combination'}, {'id': 'D004656', 'term': 'Enalapril'}, {'id': 'D000806', 'term': 'Angiotensin-Converting Enzyme Inhibitors'}], 'ancestors': [{'id': 'D008666', 'term': 'Metalloendopeptidases'}, {'id': 'D010450', 'term': 'Endopeptidases'}, {'id': 'D010447', 'term': 'Peptide Hydrolases'}, {'id': 'D006867', 'term': 'Hydrolases'}, {'id': 'D004798', 'term': 'Enzymes'}, {'id': 'D045762', 'term': 'Enzymes and Coenzymes'}, {'id': 'D045726', 'term': 'Metalloproteases'}, {'id': 'D000951', 'term': 'Antigens, Neoplasm'}, {'id': 'D000941', 'term': 'Antigens'}, {'id': 'D001685', 'term': 'Biological Factors'}, {'id': 'D014408', 'term': 'Biomarkers, Tumor'}, {'id': 'D015415', 'term': 'Biomarkers'}, {'id': 'D004151', 'term': 'Dipeptides'}, {'id': 'D009842', 'term': 'Oligopeptides'}, {'id': 'D010455', 'term': 'Peptides'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D011480', 'term': 'Protease Inhibitors'}, {'id': 'D004791', 'term': 'Enzyme Inhibitors'}, {'id': 'D045504', 'term': 'Molecular Mechanisms of Pharmacological Action'}, {'id': 'D020228', 'term': 'Pharmacologic Actions'}, {'id': 'D020164', 'term': 'Chemical Actions and Uses'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'double-blind, randomized clinical trial'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 52}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2017-06-14', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-03', 'completionDateStruct': {'date': '2020-09-23', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-10-21', 'studyFirstSubmitDate': '2017-06-14', 'studyFirstSubmitQcDate': '2017-06-14', 'lastUpdatePostDateStruct': {'date': '2020-10-22', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2017-06-16', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2020-09-14', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Exercise tolerance', 'timeFrame': '6 months', 'description': 'To test the effect of treatments on peak oxygen consumption'}], 'secondaryOutcomes': [{'measure': 'Walking distance', 'timeFrame': '6 months', 'description': 'To test the effect of treatments on 6 minutes walking test'}, {'measure': 'Muscle vasodilation', 'timeFrame': '6 months', 'description': 'To test the effect of treatments on forearm blood flow evaluated by venous occlusion plethysmography'}, {'measure': 'Muscle strength', 'timeFrame': '6 months', 'description': 'To test the effect of treatments on muscle strength evaluated by handgrip'}, {'measure': 'Body composition', 'timeFrame': '6 months', 'description': 'To test the effect of treatments on lean muscle mass evaluated by dual energy x-ray absorptiometry'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Heart Failure', 'Exercise Tolerance', 'Vasodilation', 'Body Composition', 'Muscle Strength']}, 'referencesModule': {'references': [{'pmid': '33992607', 'type': 'DERIVED', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Symptomatic patients with heart failure (men and women) aged \\>18 years,\n2. Functional class II, III or IV by the New York Heart Association (NYHA)\n3. Left ventricular ejection fraction \\<35%\n4. Ischemic and nonischemic etiology\n5. 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)\n\nExclusion Criteria:\n\n1. 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.\n2. Previous history of intolerance to recommended target doses of ACEIs or ARBs.\n3. Known history of angioedema.\n4. Requirement for treatment with both ACEIs and ARBs.\n5. Current acute decompensated heart failure (exacerbation of chronic heart failure manifested by signs and symptoms that may require intravenous therapy).\n6. Symptomatic hypotension.\n7. Estimated glomerular filtration rate (eGFR) \\<30%.\n8. Serum potassium \\>5.4 mmol/L.\n9. Acute coronary syndrome, stroke, transient ischaemic attack, cardiac, carotid, or other major cardiovascular surgery, percutaneous coronary intervention, or carotid angioplasty within the 3 months.\n10. Coronary or carotid artery disease likely to require surgical or percutaneous intervention within the 6 months.\n11. Implantation of a cardiac resynchronization therapy (CRT) device within 3 months or intent to implant a CRT.\n12. History of heart transplant or on a transplant list or with left ventricular (LV) assistance device.\n13. History of severe pulmonary disease.\n14. Diagnosis of peripartum- or chemotherapy-induced cardiomyopathy within the 12 months.\n15. Documented untreated ventricular arrhythmia with syncopal episodes within the 3 months.\n16. Symptomatic bradycardia or second- or third-degree atrioventricular block without a pacemaker.\n17. Presence of haemodynamically significant mitral and/or aortic valve disease, except mitral regurgitation secondary to LV dilatation.\n18. Presence of other haemodynamically significant obstructive lesions of the LV outflow tract, including aortic and subaortic stenosis.\n19. 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.\n20. Presence of any other disease with a life expectancy of \\<5 years.'}, 'identificationModule': {'nctId': 'NCT03190304', 'acronym': 'NEPRIExTol', 'briefTitle': 'The Effect of Neprilysin (LCZ696) on Exercise Tolerance in Patients With Heart Failure', 'organization': {'class': 'OTHER', 'fullName': 'University of Sao Paulo General Hospital'}, 'officialTitle': 'The Effect of NEPRIlysin (LCZ696) on EXercise TOLerance, Muscle Vasodilatation, Muscle Strength and Body Composition in Patients With Heart Failure - NEPRIExTol-HF Trial', 'orgStudyIdInfo': {'id': 'NEPRIExTol-HF Trial'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Enalapril', 'description': 'Enalapril at a dose of 10 mg twice daily for 6 months', 'interventionNames': ['Drug: Enalapril']}, {'type': 'EXPERIMENTAL', 'label': 'Neprilysin (LCZ696)', 'description': 'LCZ696 at a dose of 200 mg twice daily for 6 months', 'interventionNames': ['Drug: Neprilysin']}], 'interventions': [{'name': 'Neprilysin', 'type': 'DRUG', 'otherNames': ['LCZ696'], 'description': 'To compare the effect of Enalapril and Neprilysin on exercise tolerance in patients with heart failure', 'armGroupLabels': ['Neprilysin (LCZ696)']}, {'name': 'Enalapril', 'type': 'DRUG', 'otherNames': ['Angiotensin converting enzyme inhibitor'], 'description': 'To compare the effect of Enalapril and Neprilysin on exercise tolerance in patients with heart failure', 'armGroupLabels': ['Enalapril']}]}, 'contactsLocationsModule': {'locations': [{'zip': '05403-900', 'city': 'São Paulo', 'state': 'São Paulo', 'country': 'Brazil', 'facility': 'Marcelo Rodrigues dos Santos', 'geoPoint': {'lat': -23.5475, 'lon': -46.63611}}], 'overallOfficials': [{'name': 'Antonio P Barretto, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Heart Institute (InCor), University of Sao Paulo Medical School'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Sao Paulo General Hospital', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}