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
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.
Interventions
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
Contacts
Have a question?
Call 1-888-669-6682 or email [email protected]