Last Update: Sep 06, 2023
A Multicenter, Prospective, Randomized, Open-label, Blinded-endpoint, Phase 4 Study to Evaluate the Efficacy and Safety of Sacubitril/Valsartan Compared With Enalapril on Morbidity, Mortality, and NT-proBNP Change in Patients With Chronic Chagas' Cardiomyopathy
ClinicalTrials.gov Identifier:
Novartis Reference Number:CLCZ696B3302
All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.

Study Description

The purpose of this study is to evaluate the effect of sacubitril/valsartan 200 mg BID compared with enalapril 10 mg BID, in addition to conventional heart failure (HF) treatment, in improving a hierarchical composite of cardiovascular (CV) events (i.e. CV death or the occurrence of first HF hospitalization) and causing a greater reduction in n terminal prohormone of brain natriuretic peptide (NT-proBNP, at Week 12 from Baseline) in participants with HF with reduced ejection fraction (HFrEF) caused by CCC.

Chagas Disease, Heart Failure
Phase 4
Recruiting
900
Dec 10, 2019
Sep 16, 2024
All
18 Years - (Adult, Older Adult)

Interventions

Drug

Enalapril

5 mg and 10 mg will be available for dose adjustments.
Drug

Sacubitril/valsartan

50 (24/26) mg, 100 (49/51) mg and 200 (97/103) mg will be available for dose adjustments.

Eligibility Criteria

Key Inclusion Criteria:

Male or female ≥ 18 years of age

Diagnosis of NYHA Class II-IV HFrEF established by:

LVEF ≤ 40% within 12 months prior to Visit 1 made by any local measurement using echocardiography, multiple gated acquisition scan (MUGA), computerized tomography (CT) scanning, magnetic resonance imaging (MRI), or ventricular angiography, provided no subsequent measurement above 40% AND
NT-proBNP ≥ 600 pg/mL (or BNP ≥ 150 pg/mL) at Visit 1 OR
NT-proBNP ≥ 400 pg/mL (or BNP ≥ 100 pg/mL) at Visit 1 and a hospitalization for HF within the last 12 months
Chagas' disease diagnosis confirmed by at least two different serological tests for anti-Trypanosoma cruzi based on different principles or with different antigenic preparations, such as: enzyme-linked immunosorbent assay [ELISA], indirect immunofluorescence [IFI], indirect hemagglutination [IHA], western blot (WB), chemiluminescent immunoassay (CLIA). If documented history is not available, the tests may be performed during the screening

Key Exclusion Criteria:

Patients with history of suspected or proven angioedema or unable to tolerate ACEIs, ARBs or ARNI (e.g., due to cough, hypotension, renal dysfunction, hyperkalemia)
Use of sacubitril/valsartan in the past 3 months

Patients requiring continuous intravenous inotropic therapy or with indication of advanced support intervention for HF:

already on list for a heart transplantation
with current indication of left ventricular assist device, or cardiac resynchronization therapy (CRT)
Systemic systolic blood pressure lower than 95 mmHg or symptomatic hypotension
Serum potassium > 5.2 mmol/L
Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 of body surface area
Severe gastrointestinal form of chronic Chagas' disease (demonstrated megaesophagus and/or important megacolon, e.g.: with compromised oral intake or surgical indication).
Clinical conditions or systemic diseases limiting proper patient participation
Pregnant or nursing women or women of child-bearing potential unless they are using highly effective methods of contraception

Presence of other cardiac conditions:

Previous cardiac surgery
Heart failure where, in the Investigator's judgement, there is a possible alternative primary etiology e.g., due to coronary artery disease, valve disease, congenital heart disease or other causes.
Untreated arrhythmia or serious conduction disease e.g., bradyarrhythmias, atrial fibrillation with rapid ventricular response, second or third degree atrioventricular block, etc.
Primary uncorrected valvar pathology like moderate to severe aortic stenosis, mitral stenosis and primary mitral regurgitation
Planned organ transplantation (or in listing for transplantation), planned cardiac or other major surgery (including ventricular assist device implantation)
History of malignancy of any organ system within the past 5 years.
Current confirmed COVID19 infection
Past COVID19 infection with persistent symptom burden suspected due to COVID19 (persistent symptoms may include, but are not limited to, continued cough, breathing difficulty, muscle/joint aches, and gastrointestinal symptoms from the time of COVID19 infection onward)

Study Location

Novartis Investigative Site

Recruiting

Cordoba,X5003DCE,Argentina

Novartis Investigative Site

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San Miguel de Tucuman,Tucuman,T4000JCU,Argentina

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Mendoza,5500,Argentina

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Cordoba,X5004BAL,Argentina

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Santa Fe,S3000EOZ,Argentina

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Formosa,P3600,Argentina

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Mendoza,M5500CHC,Argentina

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Buenos Aires,C1155 AHD,Argentina

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Villa Maria,Cordoba,X5900JKA,Argentina

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Cordoba,X5004CDT,Argentina

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Santa Fe,S3000FWO,Argentina

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Ramos Mejia,Buenos Aires,B1704ETD,Argentina

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Temperley,Buenos Aires,1834,Argentina

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Formosa,P3600JUT,Argentina

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Buenos Aires,C1425AGP,Argentina

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Cordoba,X5006CBI,Argentina

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Formosa,P3634XAR,Argentina

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Buenos Aires,C1428DCO,Argentina

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Rosario,Santa Fe,2000,Argentina

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Cordoba,X5016KET,Argentina

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Santiago del Estero,G4200AQK,Argentina

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Tucuman,San Miguel De Tucuman,T4000ICL,Argentina

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San Martin,Buenos Aires,1604,Argentina

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Caba,Buenos Aires,C1221ADC,Argentina

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Corrientes,W3400,Argentina

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Rosario,Santa Fe,S2000DIF,Argentina

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Ciudad de Salta,Provincia De Salta,A4406BPF,Argentina

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San Miguel de Tucuman,Tucuman,T4000IFL,Argentina

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Caba,Buenos Aires,C1425BEI,Argentina

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Marilia,SP,17515-000,Brazil

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Sao Jose do Rio Preto,Sao Paulo,15015-210,Brazil

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Brasilia,DF,70390-903,Brazil

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Uberlândia,MG,38400-328,Brazil

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Ribeirao Preto,SP,14048-900,Brazil

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Goiania,GO,74223-130,Brazil

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Belo Horizonte,MG,30130-100,Brazil

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Sao Paulo,05403-000,Brazil

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Campinas,SP,13020-431,Brazil

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Salvador,BA,40110060,Brazil

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Sao Jose do Rio Preto,Sao Paulo,15015-750,Brazil

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Brasilia,Distrito Federal,70710-100,Brazil

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Rio de Janeiro,RJ,20551-030,Brazil

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Uberlandia,Minas Gerais,38411 186,Brazil

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Goiania,GO,74605-020,Brazil

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Passos,Minas Gerais,37904-020,Brazil

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Tatuí,SP,18270-170,Brazil

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Campinas,SP,13060 080,Brazil

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Salvador,BA,40323-010,Brazil

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Sao Jose do Rio Preto,SP,15090-000,Brazil

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Campinas,SP,13060-904,Brazil

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Salvador,BA,41253-190,Brazil

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Belem,PA,66087-660,Brazil

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Sao Luis,MA,65020-070,Brazil

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Rio de Janeiro,RJ,22240-006,Brazil

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Votuporanga,SP,15500 003,Brazil

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Botucatu,Sao Paulo,3880-1001,Brazil

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Ijui,98700-000,Brazil

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Recife,PE,50100-060,Brazil

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Teresina,Piaui,64001-380,Brazil

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Montes Claros,Minas Gerais,39401-001,Brazil

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Sao Paulo,01223-001,Brazil

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Braganca Paulista,Sao Paulo,13183-091,Brazil

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Indaiatuba,SP,13330-570,Brazil

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Recife,PE,52051-380,Brazil

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Belo Horizonte,MG,30140 062,Brazil

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Fortaleza,CE,60430 370,Brazil

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Natal,Rio Grande Do Norte,59020-035,Brazil

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Santo Andre,Sao Paulo,09080-001,Brazil

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Brasila,DF,70673623,Brazil

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Londrina,PR,86038-440,Brazil

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Uberaba,MG,38025-440,Brazil

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Ribeirao Preto,Sao Paulo,14010-190,Brazil

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Goiania,Goias,74223-060,Brazil

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Belo Horizonte,MG,30150-221,Brazil

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Sao Paulo,SP,04012 909,Brazil

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Salvador,BA,40050-410,Brazil

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Floridablanca,681004,Colombia

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Bogota DC,110111,Colombia

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Bogota,Cundinamarca,110121,Colombia

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Santa Marta,Magdalena,30360,Colombia

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San Gil,Santander,684031,Colombia

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Florida Blanca,681001,Colombia

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Pachuca,Hidalgo,42070,Mexico

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Guadalajara,Jalisco,44670,Mexico

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Merida,Yucatan,97000,Mexico

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Ciudad de Mexico,Cdmx,14080,Mexico

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Xalapa,91193,Mexico

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Ciudad de Mexico,Gustavo A Madero,07300,Mexico

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Oaxaca,68000,Mexico

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