Efficacy and Safety of Sacubitril/Valsartan Compared With Enalapril on Morbidity, Mortality, and NT-proBNP Change in Patients With CCC

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: NCT04023227

Novartis Reference Number: CLCZ696B3302

Last Update: Dec 06, 2021

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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.

Condition 
Chagas Disease
Heart Failure
Phase 
Phase 4
Overall status 
Recruiting
Start date 
Dec 10, 2019
Completion date 
Dec 16, 2022
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
Sacubitril/valsartan
50 (24/26) mg, 100 (49/51) mg and 200 (97/103) mg will be available for dose adjustments.
Drug
Enalapril
5 mg and 10 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 2 different serological tests for anti-Trypanosoma cruzi (enzyme-linked immunosorbent assay [ELISA], indirect immunofluorescence [IFI], and indirect hemagglutination [IHA]). 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 or ARBs (e.g., due to cough, hypotension, renal dysfunction, hyperkalemia)
Previous use of sacubitril/valsartan

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
Known gastrointestinal form of chronic Chagas' disease: demonstrated megaesophagus; important megacolon
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.

Study Locations

Argentina
Novartis Investigative Site
Recruiting
Caba, C1425BEI
Buenos Aires
Argentina
Novartis Investigative Site
Recruiting
Ramos Mejia, B1704ETD
Buenos Aires
Argentina
Novartis Investigative Site
Recruiting
San Martin, 1604
Buenos Aires
Argentina
Novartis Investigative Site
Recruiting
Temperley, 1834
Buenos Aires
Argentina
Novartis Investigative Site
Recruiting
Villa Maria, X5900JKA
Cordoba
Argentina
Novartis Investigative Site
Recruiting
Ciudad de Salta, A4406BPF
Provincia De Salta
Argentina
Novartis Investigative Site
Recruiting
Tucuman, T4000ICL
San Miguel De Tucuman
Argentina
Novartis Investigative Site
Recruiting
Rosario, 2000
Santa Fe
Argentina
Novartis Investigative Site
Recruiting
Rosario, S2000DIF
Santa Fe
Argentina
Novartis Investigative Site
Recruiting
San Miguel de Tucuman, T4000IFL
Tucuman
Argentina
Novartis Investigative Site
Recruiting
San Miguel de Tucuman, T4000JCU
Tucuman
Argentina
Novartis Investigative Site
Recruiting
Buenos Aires, C1425AGP
-
Argentina
Novartis Investigative Site
Recruiting
Buenos Aires, C1428DCO
-
Argentina
Novartis Investigative Site
Recruiting
Buenos Aires,
-
Argentina
Novartis Investigative Site
Recruiting
Cordoba, X5003DCE
-
Argentina
Novartis Investigative Site
Recruiting
Cordoba, X5004BAL
-
Argentina
Novartis Investigative Site
Recruiting
Cordoba, X5004CDT
-
Argentina
Novartis Investigative Site
Recruiting
Cordoba, X5006CBI
-
Argentina
Novartis Investigative Site
Recruiting
Cordoba, X5016KET
-
Argentina
Novartis Investigative Site
Recruiting
Corrientes, W3400
-
Argentina
Novartis Investigative Site
Recruiting
Mendoza, 5500
-
Argentina
Novartis Investigative Site
Recruiting
Mendoza, M5500CHC
-
Argentina
Novartis Investigative Site
Recruiting
Santa Fe, S3000EOZ
-
Argentina
Novartis Investigative Site
Recruiting
Santa Fe, S3000FWO
-
Argentina
Novartis Investigative Site
Recruiting
Santiago del Estero, G4200AQK
-
Argentina
Brazil
Novartis Investigative Site
Recruiting
Salvador, 40050-410
BA
Brazil
Novartis Investigative Site
Recruiting
Salvador, 40110060
BA
Brazil
Novartis Investigative Site
Recruiting
Salvador, 40323-010
BA
Brazil
Novartis Investigative Site
Recruiting
Salvador, 41253-190
BA
Brazil
Novartis Investigative Site
Recruiting
Brasila/DF, 70673623
DF
Brazil
Novartis Investigative Site
Recruiting
Brasilia, 70390-903
DF
Brazil
Novartis Investigative Site
Recruiting
Brasília,
Distrito Federal
Brazil
Novartis Investigative Site
Recruiting
Goiania,
Goiás
Brazil
Novartis Investigative Site
Recruiting
Goiania, 74223-130
GO
Brazil
Novartis Investigative Site
Recruiting
Goiania, 74605-020
GO
Brazil
Novartis Investigative Site
Recruiting
Sao Luis, 65020-070
MA
Brazil
Novartis Investigative Site
Recruiting
Belo Horizonte, 30140 062
MG
Brazil
Novartis Investigative Site
Recruiting
Belo Horizonte, 30150-221
MG
Brazil
Novartis Investigative Site
Recruiting
Uberaba, 38025-440
MG
Brazil
Novartis Investigative Site
Recruiting
Uberlândia, 38400-328
MG
Brazil
Novartis Investigative Site
Recruiting
Belo Horizonte, 30130-100
Minas Gerais
Brazil
Novartis Investigative Site
Recruiting
Passos,
Minas Gerais
Brazil
Novartis Investigative Site
Recruiting
Uberlandia, 38411 186
Minas Gerais
Brazil
Novartis Investigative Site
Recruiting
Belem, 66087-660
PA
Brazil
Novartis Investigative Site
Recruiting
Recife, 50100-060
PE
Brazil
Novartis Investigative Site
Recruiting
Recife, 52051-380
PE
Brazil
Novartis Investigative Site
Recruiting
Rio de Janeiro, 20551-030
RJ
Brazil
Novartis Investigative Site
Recruiting
Braganca Paulista,
Sao Paulo
Brazil
Novartis Investigative Site
Recruiting
Ribeirao Preto,
Sao Paulo
Brazil
Novartis Investigative Site
Recruiting
Sao Jose do Rio Preto, 15015-210
Sao Paulo
Brazil
Novartis Investigative Site
Recruiting
Sao Jose do Rio Preto,
Sao Paulo
Brazil
Novartis Investigative Site
Recruiting
Campinas, 13060 080
SP
Brazil
Novartis Investigative Site
Recruiting
Sao Jose do Rio Preto, 15090-000
SP
Brazil
Novartis Investigative Site
Recruiting
São Paulo, 05403-000
SP
Brazil
Novartis Investigative Site
Recruiting
Tatuí, 18270-170
SP
Brazil
Novartis Investigative Site
Recruiting
Votuporanga, 15500 003
SP
Brazil
Colombia
Novartis Investigative Site
Recruiting
Bogota, 110121
Cundinamarca
Colombia
Novartis Investigative Site
Recruiting
Santa Marta,
Magdalena
Colombia
Novartis Investigative Site
Recruiting
San Gil,
Santander
Colombia
Novartis Investigative Site
Recruiting
Bogota DC, 110111
-
Colombia
Novartis Investigative Site
Recruiting
Florida Blanca,
-
Colombia
Mexico
Novartis Investigative Site
Recruiting
Ciudad de Mexico, 07300
Gustavo A Madero
Mexico
Novartis Investigative Site
Recruiting
Pachuca, 42070
Hidalgo
Mexico
Novartis Investigative Site
Recruiting
Guadalajara,
Jalisco
Mexico
Novartis Investigative Site
Recruiting
Merida, 97000
Yucatán
Mexico
Novartis Investigative Site
Recruiting
Xalapa, 91193
-
Mexico

Contacts

Name: 
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Phone: 

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