Heart Failure with preserved Ejection Fraction (HFpEF) MedDRA version: 20.0 Level: LLT Classification code 10019279 Term: Heart failure System Organ Class: 100000004849
Conditions
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Left ventricular ejection fraction (LVEF) >40% by echo within 6 months prior to study entry or during the screening epoch - Symptom(s) of heart failure (HF) requiring treatment with diuretics (including loop, or thiazide diuretics, or mineralocorticoid antagonist [MRAs]) for at least 30 days prior to study entry - NYHA class II-IV - Structural heart disease (left atrial enlargement or left ventricular hypertrophy) documented by echocardiogram. - NT-proBNP > 220 pg/mL for patients with no atrial fibrillation/atrial flutter (AF) or >600 pg/mL for patients with AF - KCCQ clinical summary score =65 years) yes F.1.3.1 Number of subjects for this age range 2097
Exclusion criteria
Exclusion criteria: - Any prior measurement of LVEF = 40% under stable conditions - Acute coronary syndrome (including MI), cardiac surgery, other major CV surgery within 3 months , or urgent percutaneous coronary intervention (PCI) within 3 months or an elective PCI within 30 days prior to study entry - Any clinical event within the 6 months prior to Visit 1 that could have reduced the LVEF (e.g. MI, coronary artery bypass graft [CABG]), unless an echo measurement was performed after the event confirming the LVEF to be > 40% - Current (within 30 days from visit 1) acute decompensated HF requiring therapy. - Current (within 30 days from visit 1) use of renin inhibitor(s), dual RAS blockade or LCZ696 - History of hypersensitivity to LCZ696 or its components - Patients with a known history of angioedema - Walking distance primarily limited by non-cardiac comorbid conditions at visit 1 - Alternative reason for shortness of breath such as: significant pulmonary disease or severe COPD, hemoglobin (Hgb) 40 kg/m2. - Systolic blood pressure (SBP) = 180 mmHg at study entry, or SBP >150 mmHg and 7.5% not treated for diabetes - Patients with prior major organ transplant or intent to transplant (ie on transplant list) - eGFR 5.2 mmol /L (or equivalent plasma potassium value) at study entry - History or presence of any other disease with a life expectancy of < 3 years - Pregnant or nursing women or women of childbearing potential unless they are using highly effective methods of contraception. Other protocol-defined exclusion criteria may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Change from baseline in N-terminal pro-brain natriuretic peptide (NTproBNP) after 12 weeks Change from baseline in six-minute walk distance (6MWD) at Week 24. ; Timepoint(s) of evaluation of this end point: baseline, week 12 baseline, week 24 ; Main Objective: To demonstrate that LCZ696 is superior to individualized medical therapy for comorbidities in reducing NTproBNP from baseline after 12 weeks of treatment To demonstrate that LCZ696 is superior to individualized medical therapy for comorbidities in improving exercise capacity as assessed by the six-minute walk test (6MWT) at Week 24 in a subset of patients ; Secondary Objective: - To compare LCZ696 to individualized medical therapy for comorbidities on mean change from baseline of KCCQ clinical summary score (CSS) at Week 24 - To compare LCZ696 to individualized medical therapy for comorbidities on proportion of patients with = 5-points change in KCCQ CSS at Week 24 (= 5-points deterioration and separate analyses for = 5-points improvement) - To compare LCZ696 to individualized medical therapy for comorbidities in improving functional capacity as assessed by the 6-minute walk test (6 MWT) at Week 24 - To compare LCZ696 to individualized medical therapy for comorbidities in improving NYHA functional class at Week 24 - To compare LCZ696 to individualized medical therapy for comorbidities in improving symptoms as assessed by The Short Form (36) Health Survey (SF-36) physical component summary (PCS) score at Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Mean change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS) - Percentage of patients with = 5-points deterioration in KCCQ CSS at Week 24 - Percentage of patients with = 5-points improvement in KCCQ CSS at Week 24 - Change from baseline in the 6-minute walk test (6MWT) to week 24 - Change in NYHA functional class from baseline to week 24 - Change from baseline in SF- 36 physical component summary (PCS) score score to week 24 ;Timepoint(s) of evaluation of this end point: baseline, week 24 | — |
Countries
Argentina, Austria, Belgium, Brazil, Bulgaria, Canada, Colombia, Czech Republic, Denmark, Estonia, France, Germany, Guatemala, Hungary, India, Ireland, Israel, Italy, Latvia, Lithuania, Mexico, Netherlands, Peru, Portugal, Romania, Russian Federation, Serbia, Slovakia, Spain, Thailand, Turkey, United Kingdom, United States
Contacts
Public ContactIrena Feldmane
Novartis Baltics SIA
Outcome results
None listed