Efficacy and Safety of Sacubitril/Valsartan Compared With Enalapril on Morbidity, Mortality, and NT-proBNP Change in Patients With CCC (PARACHUTE-HF)
Chagas Disease, Heart Failure
About this trial
This is an interventional treatment trial for Chagas Disease focused on measuring Chagas' disease, heart failure, angiotensin receptor-neprilysin inhibitor, ARNI, ARB, ACEI, sacubitril/valsartan, enalapril
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)
Sites / Locations
- Novartis Investigative Site
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Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Sacubitril/valsartan
Enalapril
Sacubitril/valsartan 200 mg b.i.d. Following randomization, patients will receive sacubitril/valsartan in titrated doses from level 1 up to level 3 (50, 100 and 200 mg twice daily). Participants taking ACEIs who are randomized to sacubitril/valsartan will do a 36-hour ACEI washout before they start taking the study drug Sacubitril/valsartan in dose levels of 50 mg, 100 mg, and 200 mg are equivalent to sacubitril/valsartan 24/26 mg, 49/51 mg and 97/103 mg, respectively
Enalapril 10 mg b.i.d. Following randomization, patients will receive the enalapril in titrated doses from level 1 up to level 3 (2.5, 5 and 10 mg twice daily).