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

• Status: Recruiting
• Trial end date: 2022-12-16
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Novartis Pharmaceuticals
• Treatments: Enalapril; Enalaprilat; LCZ 696; Valsartan

Criteria

Key Inclusion Criteria:

• Male or female ≥ 18 years of age

• Diagnosis of NYHA Class II-IV HFrEF established by:

1. 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

2. NT-proBNP ≥ 600 pg/mL (or BNP ≥ 150 pg/mL) at Visit 1 OR

3. 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:

1. already on list for a heart transplantation

2. 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:

1. Previous cardiac surgery

2. 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.

3. Untreated arrhythmia or serious conduction disease e.g., bradyarrhythmias, atrial fibrillation with rapid ventricular response, second or third degree atrioventricular block, etc.

4. Primary uncorrected valvar pathology like moderate to severe aortic stenosis, mitral stenosis and primary mitral regurgitation

5. 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.