Heart Failure with preserved ejection fraction (HF-pEF) MedDRA version: 20.0 Level: LLT Classification code 10019279 Term: Heart failure System Organ Class: 100000004849
Conditions
Interventions
Trade Name: Entresto
Product Name: Entresto
Product Code: LCZ696 50 mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: sacubitril/valsartan
Other descriptive name: SACUBITRIL VALSARTAN
Co
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent including consent for APOE4 gene testing must be obtained before any assessment is performed 2. Male or female patients aged = 60 years of age. 3. Chronic heart failure with current symptom(s) (NYHA class II-IV) at Screening visit. 4. LVEF > 40% a. By any method using most recent assessment within 6 months prior to screening visit OR b. By an echocardiogram performed during the screening visit, if previous assessment is not available. 5. NT-proBNP = 125 pg/mL at Screening visit 6. Patient with evidence of adequate functioning (e.g.: intellectual, motor, visual and auditory) to complete the study assessments and has elementary education or 6 years of sustained employment. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 75 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 445
Exclusion criteria
Exclusion criteria: 1. Current acute decompensated HF requiring augmented therapy with diuretics, vasodilators and/or inotropic drugs. 2. Acute coronary syndrome (including myocardial infarction (MI)), cardiac surgery, other major cardiovascular (CV) surgery, or urgent percutaneous coronary intervention (PCI), carotid surgery or carotid angioplasty, history of stroke or transient ischemic attack within the 3 months prior to Screening visit or an elective PCI within 30 days prior to Screening visit. 3. Patients with history of hereditary or idiopathic angioedema or angioedema related to previous angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) therapies. 4. Patients who require treatment with 2 or more of the following: an ACEi, an ARB or a renin inhibitor. 5. Patients with one of the following: a. Estimated glomerular filtration rate (eGFR) 35% (compared to Visit 1) at Visit 103 or Visit 199/201 6. MMSE score 3 minutes within 6 months prior to screening, Huntington’s disease, Parkinson’s disease, Lyme’s disease, syphilis, HIV dementia, uncontrolled seizure disorder) or clinically significant abnormalities in thyroid function tests, Vitamin B12 or folate deficiency requiring treatment at screening. (Patients who are adequately treated may be included at investigator discretion). 9. Inability to perform cognitive battery or other study evaluations based on significant motor (e.g. hemiplegia, muscular-skeletal injury) or sensory (blindness, decreased or uncorrected visual or auditory acuity) skill. 10. Score “yes” on item 4 or item 5 of the Suicidal Ideation section of the Columbia suicidality severity rating scale (C-SSRS), if this ideation occurred in the past 6 months, or “yes” on any item of the Suicidal Behavior section, except for the “Non-Suicidal Self-Injurious Behavior” (item also included in the Suicidal Behavior section), if this behavior occurred in the past 2 years. 11. Clinically significant cerebral pathology, for example large cerebral aneurysm, space occupying lesion etc. that may impact cognition as assessed by MRI central reader. 12. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes. 13. History or presence of any other disease with a life expectancy of <3 years 14. Women of child bearing potential defined as all women physiologically capable of becoming pregnant.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Change from baseline to 3 years in the CogState Global Cognitive Composite Score (GCCS);Timepoint(s) of evaluation of this end point: From baseline to 3 years ;Secondary Objective: To evaluate the effect of LCZ696 compared to valsartan on Beta-amyloid deposition in the brain in a subset of patients using amyloid positron emission tomography (PET) imaging over 3 years. To evaluate the effects of LCZ696 compared to valsartan on individual cognitive domains (memory, executive function, and attention) as assessed by the individual components of the CogState battery over 3 years. To compare LCZ696 to valsartan in evaluating changes in instrumental activities of daily living (IADL) as assessed with Functional Activity Questionnaire (FAQ) over 3 years.;Main Objective: To evaluate the effects of LCZ696 compared to valsartan on cognitive function over 3 years in patients with HFpEF as assessed by the CogState cognitive assessment battery. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Change from baseline in a cortical composite SUVr (standardized uptake value ratio) at 3 years - Change from baseline in individual cognitive domains (memory, executive function, and attention) as assessed by the individual components of the cognitive assessment battery at 3 years - Change from baseline in the summary score of the instrumental activities of daily living (IADL) as assessed with Functional Activity Questionnaire (FAQ) at 3 years ;Timepoint(s) of evaluation of this end point: From baseline to 3 years | — |
Countries
Argentina, Belgium, Bulgaria, Canada, Croatia, France, Germany, Italy, Lithuania, Netherlands, Poland, Russian Federation, Spain, Switzerland, Turkey, United Kingdom, United States
Contacts
Public ContactMedica Information Services
Novartis Pharmaceuticals UK Limited
Outcome results
None listed