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

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)